bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antibiotic Efflux Protein TolC Is a Highly Evolvable Target under Colicin E1 or TLS Phage Selection
Authors: Tamer Yusuf Talha , Gaszek Ilona , Rodrigues Marinelle , Coskun Fatma Sevde , Farid Michael , Koh Andrew Y , Russ William , Toprak Erdal
Published: June 2021

Bacteriophages and bacterial toxins are promising antibacterial agents to treat infections caused by multidrug-resistant (MDR) bacteria. In fact, bacteriophages have recently been successfully used to treat life-threatening infections caused by MDR bacteria (Schooley RT, Biswas B, Gill JJ, Hernandez-Morales A, Lancaster J, Lessor L, Barr JJ, Reed SL, Rohwer F, Benler S, et al. 2017. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob Agents Chemother. 61(10); Chan BK, Turner PE, Kim S, Mojibian HR, Elefteriades JA, Narayan D. 2018. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol Med Public Health. 2018(1):60–66; Petrovic Fabijan A, Lin RCY, Ho J, Maddocks S, Ben Zakour NL, Iredell JR, Westmead Bacteriophage Therapy Team. 2020. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat Microbiol. 5(3):465–472). One potential problem with using these antibacterial agents is the evolution of resistance against them in the long term. Here, we studied the fitness landscape of the Escherichia coli TolC protein, an outer membrane efflux protein that is exploited by a pore forming toxin called colicin E1 and by TLS phage (Pagie L, Hogeweg P. 1999. Colicin diversity: a result of eco-evolutionary dynamics. J Theor Biol. 196(2):251–261; Andersen C, Hughes C, Koronakis V. 2000. Chunnel vision. Export and efflux through bacterial channel-tunnels. EMBO Rep. 1(4):313–318; Koronakis V, Andersen C, Hughes C. 2001. Channel-tunnels. Curr Opin Struct Biol. 11(4):403–407; Czaran TL, Hoekstra RF, Pagie L. 2002. Chemical warfare between microbes promotes biodiversity. Proc Natl Acad Sci U S A. 99(2):786–790; Cascales E, Buchanan SK, Duché D, Kleanthous C, Lloubès R, Postle K, Riley M, Slatin S, Cavard D. 2007. Colicin biology. Microbiol Mol Biol Rev. 71(1):158–229). By systematically assessing the distribution of fitness effects of ∼9,000 single amino acid replacements in TolC using either positive (antibiotics and bile salts) or negative (colicin E1 and TLS phage) selection pressures, we quantified evolvability of the TolC. We demonstrated that the TolC is highly optimized for the efflux of antibiotics and bile salts. In contrast, under colicin E1 and TLS phage selection, TolC sequence is very sensitive to mutations. Finally, we have identified a large set of mutations in TolC that increase resistance of E. coli against colicin E1 or TLS phage without changing antibiotic susceptibility of bacterial cells. Our findings suggest that TolC is a highly evolvable target under negative selection which may limit the potential clinical use of bacteriophages and bacterial toxins if evolutionary aspects are not taken into account.
Kmerator Suite: design of specific k-mer signatures and automatic metadata discovery in large RNA-seq datasets
Authors: Riquier Sébastien , Bessiere Chloé , Guibert Benoit , Bouge Anne-Laure , Boureux Anthony , Ruffle Florence , Audoux Jérôme , Gilbert Nicolas , Xue Haoliang , Gautheret Daniel , Commes Thérèse
Published: June 2021

The huge body of publicly available RNA-sequencing (RNA-seq) libraries is a treasure of functional information allowing to quantify the expression of known or novel transcripts in tissues. However, transcript quantification commonly relies on alignment methods requiring a lot of computational resources and processing time, which does not scale easily to large datasets. K-mer decomposition constitutes a new way to process RNA-seq data for the identification of transcriptional signatures, as k-mers can be used to quantify accurately gene expression in a less resource-consuming way. We present the Kmerator Suite, a set of three tools designed to extract specific k-mer signatures, quantify these k-mers into RNA-seq datasets and quickly visualize large dataset characteristics. The core tool, Kmerator, produces specific k-mers for 97% of human genes, enabling the measure of gene expression with high accuracy in simulated datasets. KmerExploR, a direct application of Kmerator, uses a set of predictor gene-specific k-mers to infer metadata including library protocol, sample features or contaminations from RNA-seq datasets. KmerExploR results are visualized through a user-friendly interface. Moreover, we demonstrate that the Kmerator Suite can be used for advanced queries targeting known or new biomarkers such as mutations, gene fusions or long non-coding RNAs for human health applications.
Critical Presentation of a Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection: A Case Report
Authors: Massanella Marta , Martin-Urda Anabel , Mateu Lourdes , Marín Toni , Aldas Irene , Riveira-Muñoz Eva , Kipelainen Athina , Jiménez-Moyano Esther , Rodriguez de la Concepción Maria Luisa , Avila-Nieto Carlos , Trinité Benjamin , Pradenas Edwards , Rodon Jordi , Marfil Silvia , Parera Mariona , Carrillo Jorge , Blanco Julià , Prado Julia G , Ballana Ester , Vergara-Alert Júlia , Segalés Joaquim , Noguera-Julian Marc , Masabeu Àngels , Clotet Bonaventura , Toda Maria de la Roca , Paredes Roger
Published: June 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections have been reported; however, most cases are milder than the primary infection. We report the first case of a life-threatening critical presentation of a SARS-CoV-2 reinfection.

Methods

A 62-year-old man from Palamós (Spain) suffered a first mild coronavirus disease 2019 (COVID-19) episode in March 2020, confirmed by 2 independent SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) assays and a normal radiograph. He recovered completely and tested negative on 2 consecutive PCRs. In August 2020, the patient developed a second SARS-CoV-2 infection with life-threatening bilateral pneumonia and Acute respiratory distress syndrome criteria, requiring COVID-19–specific treatment (remdesivir + dexamethasone) plus high-flow oxygen therapy. Nasopharyngeal swabs from the second episode were obtained for virus quantification by real-time PCR, for virus outgrowth and sequencing. In addition, plasma and peripheral blood mononuclear cells during the hospitalization period were used to determine SARS-CoV-2–specific humoral and T-cell responses.

Results

Genomic analysis of SARS-CoV-2 showed that the virus had probably originated shortly before symptom onset. When the reinfection occurred, the subject showed a weak immune response, with marginal humoral and specific T-cell responses against SARS-CoV-2. All antibody isotypes tested as well as SARS-CoV-2 neutralizing antibodies increased sharply after day 8 postsymptoms. A slight increase of T-cell responses was observed at day 19 after symptom onset.

Conclusions

The reinfection was firmly documented and occurred in the absence of robust preexisting humoral and cellular immunity. SARS-CoV-2 immunity in some subjects is unprotective and/or short-lived; therefore, SARS-CoV-2 vaccine schedules inducing long-term immunity will be required to bring the pandemic under control.
Social Determinants of Health and Care Outcomes Among People With HIV in the United States
Authors: Menza Timothy W , Hixson Lindsay K , Lipira Lauren , Drach Linda
Published: June 2021

Background

Fewer than 70% of people with HIV (PWH) in the United States have achieved durable viral suppression. To end the HIV epidemic in the United States, clinicians, researchers, and public health practitioners must devise ways to remove barriers to effective HIV treatment. To identify PWH who experience challenges to accessing health care, we created a simple assessment of social determinants of health (SDOH) among PWH and examined the impact of cumulative social and economic disadvantage on key HIV care outcomes.

Methods

We used data from the 2015–2019 Medical Monitoring Project, a yearly cross-sectional survey of PWH in the United States (n = 15 964). We created a 10-item index of SDOH and assessed differences in HIV care outcomes of missed medical appointments, medication adherence, and durable viral suppression by SDOH using this index using prevalence ratios with predicted marginal means.

Results

Eighty-three percent of PWH reported at least 1 SDOH indicator. Compared with PWH who experienced none of the SDOH indicators, people who experienced 1, 2, 3, and 4 or more SDOH indicators were 1.6, 2.1, 2.6, and 3.6 as likely to miss a medical appointment in the prior year; 11%, 17%, 20%, and 31% less likely to report excellent adherence in the prior 30 days; and 2%, 4%, 10%, and 20% less likely to achieve durable viral suppression in the prior year, respectively.

Conclusions

Among PWH, cumulative exposure to social and economic disadvantage impacts care outcomes in a dose-dependent fashion. A simple index may identify PWH experiencing barriers to HIV care, adherence, and durable viral suppression in need of critical supportive services.
Real-world Effectiveness and Tolerability of Monoclonal Antibody Therapy for Ambulatory Patients With Early COVID-19
Authors: Webb Brandon J , Buckel Whitney , Vento Todd , Butler Allison M , Grisel Nancy , Brown Samuel M , Peltan Ithan D , Spivak Emily S , Shah Mark , Sakata Theadora , Wallin Anthony , Stenehjem Eddie , Poulsen Greg , Bledsoe Joseph
Published: June 2021

Background

Neutralizing monoclonal antibodies (MAbs) are a promising therapy for early coronavirus disease 2019 (COVID-19), but their effectiveness has not been confirmed in a real-world setting.

Methods

In this quasi-experimental pre-/postimplementation study, we estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk ambulatory adults with COVID-19. The primary outcome was a composite of emergency department visits or hospitalizations within 14 days of positive test. Secondary outcomes included adverse events and 14-day mortality. The average treatment effect in the treated for MAb therapy was estimated using inverse probability of treatment weighting and the impact of MAb implementation using propensity-weighted interrupted time series analysis.

Results

Pre-implementation (July–November 2020), 7404 qualifying patients were identified. Postimplementation (December 2020–January 2021), 594 patients received MAb treatment and 5536 did not. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) historical controls. MAb treatment was associated with decreased likelihood of emergency care or hospitalization (odds ratio, 0.69; 95% CI, 0.60–0.79). After implementation, the weighted probability that a given patient would require an emergency department visit or hospitalization decreased significantly (0.7% per day; 95% CI, 0.03%–0.10%). Mortality was 0.2% (n = 1) in the MAb group compared with 1.0% (n = 71) and 1.0% (n = 57) in pre- and postimplementation controls, respectively. Adverse events occurred in 7 (1.2%); 2 (0.3%) were considered serious.

Conclusions

MAb treatment of high-risk ambulatory patients with early COVID-19 was well tolerated and likely effective at preventing the need for subsequent emergency department or hospital care.
Pre-Visit Education on Pain Management Options Prior to the First Clinic Visit Improves Chronic Pain Patient Satisfaction with Proposed Treatment Plans
Authors: Unnithan Ajay S , Chidgey Brooke A
Published: June 2021

Objective

This study sought to evaluate if actively informing new chronic pain patients about treatment options and setting realistic expectations for care, through the use of a pre-visit informational handout prior to the first clinic visit, improved patient satisfaction with subsequently proposed treatment plans.

Methods

The study was divided into two 3-month periods. During the first 3 months, with our current pain clinic practices in place, new patients (n = 147) were given surveys to establish a baseline of patient satisfaction with treatment plans proposed on their first visit. During the second 3 months, a different group of new patients (n = 156) was given a detailed informational handout which described our clinic’s multimodal approach to pain management and therapeutic expectations prior to their visit with a provider. Patient satisfaction with subsequently proposed treatment plans was then assessed and compared with the baseline group.

Results

The average patient satisfaction score for the group of patients given the informational handout was 4.21 (on a 5-point Likert scale), compared to an average score of 3.25 for the baseline group (P < .0001, unpaired t-test). 77.6% of patients given the informational handout said their proposed treatment plan met their expectations compared to 46.3% of patients in the baseline group (χ2= 31.61, two-tailed P < .0001).

Conclusions

Patient satisfaction with proposed chronic pain treatment plans was improved when clinic approaches to pain were explicitly outlined and therapeutic expectations were clearly established in the form of an informational handout at the outset of the first visit.
Differential Pain Presentations Observed across Post-Traumatic Stress Disorder Symptom Trajectories after Combat Injury
Authors: Giordano Nicholas A , Richmond Therese S , Farrar John T , ‘Trip’ Buckenmaier III Chester C , Gallagher Rollin M , Polomano Rosemary C
Published: June 2021

Objective

This study evaluated the association between pain outcomes and post-traumatic stress disorder (PTSD) symptom trajectories after combat-related injury, while adjusting for receipt of regional anesthesia (RA) soon after injury.

Methods

The PTSD symptom trajectories of N = 288 combat-injured service members were examined from within a month of injury up to two-years after. Linear mixed-effects models evaluated the association between PTSD symptom trajectories and average pain and pain interference outcomes while adjusting for receipt of RA during combat casualty care.

Results

Four PTSD trajectories were characterized: resilient, recovering, worsening, and chronic. Differential pain presentations were associated with PTSD symptom trajectories, even after adjusting for receipt of RA. Compared to those with a resilient PTSD symptom trajectory, individuals presenting with chronic PTSD trajectories were estimated to experience average pain scores 2.61 points higher (95% CI: 1.71, 3.14). Participants presenting with worsening (β = 1.42; 95% CI: 0.77, 1.78) and recovering PTSD trajectories (β = 0.65; 95% CI: 0.09, 1.08) were estimated to experience higher average pain scores than participants with resilient PTSD trajectories. Significant differences in pain interference scores were observed across PTSD trajectories. Receiving RA was associated with improved pain up to two years after injury (β = -0.31; 95% CI: -0.90, -0.04), however no statistically significant association was detected between RA and PTSD trajectories.

Conclusions

Chronic and worsening PTSD trajectories were associated with greater pain intensity and interference following combat injury even when accounting for receipt of early RA for pain management. These findings underscore the need to jointly assess pain and PTSD symptoms across the trauma care continuum.
TIME, AND TIME AGAIN
Authors: Baron Sam , Lin Yi-Cheng
Published: June 2021

A number of philosophers uphold a metaphysical symmetry between time and hypertime, in this sense: in so far as hypertime exists, the nature of hypertime should agree with the nature of time. Others allow that we can mix and match the metaphysics of time and hypertime. Thus, it may be that time really passes, but hypertime does not or vice versa. In this paper, we provide a preliminary defense of the mix and match approach. We outline a number of arguments for the claim that time and hypertime must share a common nature and find them all wanting.
Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody–positive individuals
Authors: Muñoz-Grajales Carolina , Prokopec Stephenie D , Johnson Sindhu R , Touma Zahi , Ahmad Zareen , Bonilla Dennisse , Hiraki Linda , Bookman Arthur , Boutros Paul C , Chruscinski Andrzej , Wither Joan
Published: June 2021

Objective

We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals.

Methods

Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset.

Results

We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not.

Conclusion

Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.
Is the Association Between Parents’ Mental Illness and Child Psychopathology Mediated via Home Environment and Caregiver’s Psychosocial Functioning? A Mediation Analysis of the Danish High Risk and Resilience Study—VIA7, a Population-Based Cohort Study
Authors: Uddin Md Jamal , Ekstrøm Claus Thorn , Hemager Nicoline , Christiani Camilla A J , Gregersen Maja , Ellersgaard Ditte Vestbjerg , Spang Katrine Søborg , Greve Aja , Gantriis Ditte Lou , Burton Birgitte Klee , Søndergaard Anne , Nudel Ron , Mortensen Preben Bo , Pedersen Marianne Giørtz , Pedersen Carsten Bøcker , Wang Yunpeng , Werge Thomas , Bybjerg-Grauholm Jonas , von Plessen Kerstin J , Bliksted Vibeke , Mors Ole , Thorup Anne A E , Nordentoft Merete
Published: June 2021

We aimed to investigate to which degree the home environment and/or primary caregivers’ level of functioning mediate the association between parental mental illness (eg, schizophrenia) and child psychopathology. We used data from the nationwide Danish High Risk and Resilience Study—VIA7. The study sample comprised 522 seven-year-old children. The main outcome was the child psychopathology, assessed with the Child Behavior Checklist (CBCL). The exposure variable had 3 categories: children at familial high risk of schizophrenia spectrum psychosis (FHR-SZ), bipolar disorder (FHR-BP), and population-based controls. Mediators were quality of the Home Observation for Measurement of the Environment (HOME) and primary caregiver’s Personal and Social Performance Scale (primary caregiver functioning). Primary caregiver’s IQ and polygenic risk scores (PRS) for the educational attainment of the children were considered as covariates. We found a significant indirect adjusted effect of FHR status vs controls on CBCL total scores (FHR-SZ = 5.34, 95% confidence interval [CI]: 3.50–7.47 and FHR-BP = 4.54, 95% CI: 2.65–6.68), through primary caregiver functioning and HOME. Both mediators combined explained 53% and 64% variation of the total effects of FHR-SZ and FHR-BP, respectively. Adjusting for the PRS in the mediation models only resulted in minor changes in the FHR effects on the CBCL. We conclude that the HOME and the primary caregiver functioning are important mediating factors for child psychopathology, especially in children born with familial risk for severe mental illness. This knowledge may represent a window of opportunity for the development of preventive strategies (eg, intervention to improve primary caregiver functioning and home environment).
A nationwide cross-sectional study of difficulty waking up for school among adolescents
Authors: Kinoshita Yu , Itani Osamu , Otsuka Yuichiro , Matsumoto Yuuki , Nakagome Sachi , Osaki Yoneatsu , Higuchi Susumu , Maki Jike , Kanda Hideyuki , Kaneita Yoshitaka
Published: June 2021

Study Objectives

To determine the prevalence of and risk-factors for difficulty waking up for school among adolescents.

Methods

We used a self-administered questionnaire (140 junior high schools [JHSs]; 124 senior high schools [SHSs]) selected randomly in 2012 from throughout Japan.

Results

Total response rate: 60.7%. Data from 38 494 JHS and 61 556 SHS students were analyzed. The prevalence of at least one instance of school tardiness/absence due to difficulty waking up over a 30-day period was 10.9 (95% confidence-interval:10.5–11.3)%/2.9(2.7–3.1)% for JHS-boys and 7.7(7.3–8.1)%/2.0(1.8–2.2)% for JHS-girls. The prevalence was 15.5(15.1–15.9)%/5.6(5.3–5.9)% for SHS-boys and 14.4(14.0–14.8)%/5.9(5.6–6.2)% for SHS-girls. We used ordinal regression to identify the risk factors associated with the experience of school tardiness/absence. Factors significantly associated with school tardiness in all four groups (JHS boys/girls, SHS boys/girls) were “no-participation-in-club-activities,” “early-morning-awakening,” “feeling bad throughout a morning,” “drinking,” and “smoking.” Among associated factors, the highest odds ratio was found for monthly smoking-days (none vs. at least one-day or more) for JHS-girls at 5.30(3.57–7.85). Factors significantly associated with school absence in all four groups were “no wishing to go to university,” “no participation in club activities,” “disorders of initiating and maintaining sleep,” “long internet use,” “drinking,” “smoking,” “poor-mental-health” and “feeling bad throughout a morning.” Among associated factors, the highest odds ratio was found for monthly smoking-days (none vs. at least one-day or more) for JHS-girls at 4.60(3.45–6.15).

Conclusions

These results suggest that the risk factors for difficulty waking up among adolescents are sleep status, lifestyle, and mental health, which can indicate the presence of an underlying disease.
IX The Seventeenth Century: Part I
Authors: Baker William , Gwynn Lucy , Doelman James , James Anne , Urban David
Published: June 2021

This chapter combines what previously were Chapter IX, focusing on the early seventeenth century, and Chapter X, on Milton and poetry 1603–1660. Some of the content transcends historical dates and covers material from the latter half of the seventeenth century too; in other words, the long seventeenth century. It has seven sections:1. General; 2. Bacon; 3. Browne; 4. Burton; 5. Herbert; 6. Donne; 7. Milton. Sections 1 and 2 are by William Baker; section 3 is by Lucy Gwynn; section 4 is by William Baker; section 5 is by James Doelman; section 6 is by Anne James; section 7 is by David Urban.
Molecular Assessment of Pathotype Diversity of Phytophthora sojae in Canada Highlights Declining Sources of Resistance in Soybean
Authors: Tremblay Vanessa , McLaren Debra L. , Kim Yong Min , Strelkov Stephen E. , Conner Robert L. , Wally Owen , Bélanger Richard R.
Published: June 2021

The large-scale deployment of resistance to Phytophthora sojae (Rps) genes in soybean has led to the rapid evolution of the virulence profile (pathotype) of P. sojae populations. Determining the pathotypes of P. sojae isolates is important in selecting soybean germplasm carrying the proper Rps, but this process is fastidious and requires specific expertise. In this work, we used a molecular assay to assess the pathotypes of P. sojae isolates obtained throughout the provinces of Québec, Ontario, and Manitoba. In preliminary assays, the molecular tool showed equivalent prediction of the pathotypes as a phenotyping assay and proved to be much faster to apply while eliminating intermediate values. Upon analysis of nearly 300 isolates, 24 different pathotypes were detected in Québec and Ontario, compared with only eight in Manitoba, where soybean culture is more recent. Pathotypes 1a, 1c, and 1d was predominant in Québec, while 1a, 1b, 1c, 1d, and 1k pathotypes were the most common in Manitoba. Overall, the results showed that 98 and 86% of the isolates carried pathotype 1a or 1c, respectively, suggesting that Rps1a and Rps1c were no longer effective in Canada. Based on the history of soybean varieties used in surveyed fields, it was found that 84% of them contained Rps genes that were no longer resistant against the pathotypes of the isolates found in the fields. While highlighting an easier and more precise option to assess pathotypes, this study presents the first pan-Canadian survey of P. sojae and stresses the importance of carefully managing the declining sources of resistance.
Underutilization of Cardiac Rehabilitation in Women
Authors: Khadanga Sherrie , Gaalema Diann E. , Savage Patrick , Ades Philip A.
Published: June 2021

Purpose:

Despite the known benefits of cardiac rehabilitation (CR), it remains underutilized particularly among women. The aim of this review was to provide an overview regarding women in CR, addressing barriers that may affect enrollment and attendance as well as to discuss the training response and methods to optimize exercise-related benefits of CR.

Review Methods:

The review examines original studies and meta-analyses regarding women in CR.

Women are less likely to engage in CR compared with men, and this may be attributed to lack of referral or psychosocial barriers on the part of the patient. Furthermore, despite having lower levels of fitness, women do not improve their fitness as much as men in CR. This review summarizes the current literature and provides recommendations for providers regarding participation and adherence as well as optimal methods for exercise training for women in CR.
The Cox model of predicting mortality among melioidosis patients in Northern Malaysia
Authors: Mardhiah Kamaruddin , Wan-Arfah Nadiah , Naing Nyi Nyi , Hassan Muhammad Radzi Abu , Chan Huan-Keat
Published: June 2021

Melioidosis is an infectious disease that is initiated by a bacteria recognized as Burkholderia pseudomallei. Despite the high fatality rate from melioidosis, there is a minimal published study about the disease in Malaysia.

This study aimed to identify the prognostic factors of mortality among melioidosis patients in northern Malaysia.

All inpatient patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis with culture-confirmed melioidosis during the period 2014 to 2017 were included in the study. The study retrospectively collected 510 melioidosis patients from the Melioidosis Registry. Hazard ratio (HR) used in advanced multiple Cox regression was used to obtain the final model of prognostic factors of melioidosis. The analysis was performed using STATA/SE 14.0 for Windows software.

From the results, among the admitted patients, 50.1% died at the hospital. The mean age for those who died was 55 years old, and they were mostly male. The most common underlying disease was diabetes mellitus (69.8%), followed by hypertension (32.7%). The majority of cases (86.8%) were bacteremic. The final Cox model identified 5 prognostic factors of mortality among melioidosis patients. The factors were diabetes mellitus, type of melioidosis, platelet count, white blood cell count, and urea value. The results showed that bacteremic melioidosis increased the risk of dying by 3.47 (HR: 3.47, 95% confidence intervals [CI]: 1.67–7.23, P = .001) compared to non-bacteremic melioidosis. Based on the blood investigations, the adjusted HRs from the final model showed that all 3 blood investigations were included as the prognostic factors for the disease (low platelet: HR = 1.76, 95% CI: 1.22–2.54, P = .003; high white blood cell: HR = 1.49, 95% CI 1.06–2.11, P = .023; high urea: HR = 2.92, 95% CI: 1.76–4.85, P < .001; and low level of urea: HR = 2.69, 95% CI: 1.69–4.29, P < .001). By contrast, melioidosis patients with diabetic had 30.0% lower risk of dying from melioidosis compared to those with non-diabetic (HR = 0.70, 95% CI: 0.52–0.94, P = .016).

Identifying the prognostic factors of mortality in patients with melioidosis allows a guideline of early management in these patients, which may improve patient's survival.
Simulated versus physical bench tests
Authors: Mincarone Pierpaolo , Bodini Antonella , Sabina Saverio , Colella Riccardo , Tumolo Maria Rosaria , Fawdry Martin , Fotiadis Dimitrios I. , Leo Carlo Giacomo
Published: June 2021

Background:

In silico medicine allows for pre-clinical and clinical simulated assessment of medical technologies and the building of patient-specific models to support medical decisions and forecast personal health status. While there is increasing trust in the potential central role of in silico medicine, there is a need to recognize its degree of reliability and evaluate its economic impact. An in silico platform has been developed within a Horizon 2020-funded project (In-Silc) for simulations functional to designing, developing, and assessing drug-eluting bioresorbable vascular scaffolds.

The main purpose of this study was to compare the costs of 2 alternative strategies: the adoption of In-Silc platform versus the performance of only physical bench tests.

Methods:

A case study was provided by a medical device company. The values of the model parameters were principally set by the project partners, with use of interviews and semi-structured questionnaires, and, when not available, through literature searches or derived by statistical techniques. An economic model was built to represent the 2 scenarios.

Results:

The InSilc strategy is superior to the adoption of physical bench tests only. Ceteris paribus, the costs are 424,355€ for the former versus 857,811€ for the latter.

Conclusions:

In silico medicine tools can decrease the cost of the research and development of medical devices such as bioresorbable vascular scaffolds. Further studies are needed to explore the impact of such solutions on the innovation capacity of companies and the consequent potential advantages for target patients and the healthcare system.
Meta-analysis on aspirin combined with low-molecular-weight heparin for improving the live birth rate in patients with antiphospholipid syndrome and its correlation with d-dimer levels
Authors: Shi Ting , Gu Zhong-Deng , Diao Qi-zhi
Published: June 2021

Background:

Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer.

Methods:

The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The “Risk of Bias Assessment” tool and the “Jadad Scale” provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software.

Results:

In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22–1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09–1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results.

Conclusion:

Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants.
High-dose statin pretreatment decreases periprocedural myocardial infarction and cardiovascular events in East Asian patients undergoing percutaneous coronary intervention
Authors: Liu Jiahui , Zhang Bin , Chen Ming , Zheng Bo
Published: June 2021

Background:

Numerous studies have shown that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and short-term major adverse cardiac events (MACE) in western people undergoing percutaneous coronary intervention (PCI). However, the effects in East Asian patients are still controversial. The objective was to evaluate the effects of short-term high-dose statin (all types) pretreatment compared with the control (low-dose or no statin) on the reduction of the rate of MACE and PMI in East Asian patients.

Methods:

PubMed/Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) in East Asian patients up to December 2019, in which short-term high-dose statin pretreatment was compared with control for patients undergoing PCI. The primary outcome measure was the incidence of MACE at 30 days. The secondary outcome measure was the incidence of PMI. The meta-analysis was performed with the fixed-effect model or random-effects model according to the heterogeneity. The meta-analysis was performed using RevMan 5.3 software (Cochrane Collaboration).

Results:

Fifteen RCTs that enrolled 4313 East Asian patients were identified. High-dose statin pretreatment was associated with a 54% relative reduction in 30-day MACE (OR, 0.46; 95% CI, 0.31–0.67; P < .001) and a 50% relative reduction in PMI (OR, 0.50; 95% CI, 0.34–0.76; P = .001).

Conclusions:

High-dose statin pretreatment can significantly reduce 30-day MACE and PMI for East Asian patients undergoing PCI.
The efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for postoperative pain in laparoscopy
Authors: Meng Dan , Mao Yifei , Song Quanmei , Yan Chunchun , Zhao Qinyu , Yang Mengqi , Song Yongmei
Published: June 2021

Background:

With the promotion of the concept of “minimally invasive” surgery, the advantages of laparoscopic surgery are increasingly manifested. However, the postoperative pain of laparoscopic surgery brings difficulties and challenges to patients’ rehabilitation. Transcutaneous electrical acupoint stimulation (TEAS) is a non-invasive treatment, which can exert the dual efficacy of acupuncture and electrical stimulation. The efficacy and safety of TEAS for postoperative pain after laparoscopy based on randomized controlled trials (RCTs) need to further evaluate.

Methods:

A comprehensive and systematic literature searching will mainly perform on 7 electronic databases (PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP Information, WanFang Data, and Chinese Biomedical Database) from their inception up to November 30, 2020. We will also search for ongoing or unpublished studies from other websites (eg, PROSPERO, ClinicalTrials.gov, and Chinese Clinical Trial Registry) and do manual retrieval for potential gray literature. Only the relevant RCTs published in English or Chinese were included. Two independent investigators will independently complete literature selection, assessment of risk bias, and data extraction, the disagreements will be discussed with the third party for final decisions. The primary outcome measures: the pain intensity (eg, VAS) and the consumption of postoperative analgesics. The secondary outcome measures: the postoperative quality of life, the duration of hospitalization, and the incidence of adverse reactions and serious events. Assessment of bias risk will follow the Cochrane risk of bias tool. Data processing will be conducted by Stata 15.0 software.

Results:

We will evaluate the efficacy and safety of TEAS for postoperative pain after laparoscopy based on RCTs.

Conclusion:

This study can provide more comprehensive and strong evidence of whether TEAS is efficacy and safe for postoperative pain in laparoscopic surgery.
Impact of premature natural menopause on body composition and physical function in elderly women
Authors: Cho Hangyeol , Gu Min Su , Won Chang Won , Kong Hyun Ho
Published: June 2021

Induced premature menopause accelerates the rate of body composition changes (decrease in skeletal muscle mass and increase in fat mass) and deteriorating physical function. However, few studies have focused on the impact of premature natural menopause. This study aimed to investigate the impact of age at natural menopause (ANM) on body composition and physical function in elderly women.

Using data from the Korean Frailty and Aging Cohort Study, 765 community-dwelling elderly women aged 70 to 85 years who experienced natural menopause were recruited in this study. Body composition was measured using dual-energy X-ray absorptiometry. Physical function was evaluated by grip strength, the timed up and go test (TUG), and the short physical performance battery (SPPB). Participants were categorized into 4 groups according to their ANM: <40 (premature natural menopause, PNM), 40 to 44 (early natural menopause, ENM), 45 to 54 (normal menopause, NM), and ≥55 (late menopause, LM) years.

There were no significant differences in the body composition parameters, such as the appendicular skeletal muscle mass index (PNM: 5.90 ± 0.90 vs ENM: 5.91 ± 0.70 vs NM: 5.85 ± 0.73 vs LM: 5.90 ± 0.75, kg/m2, P = .75) and trunk fat mass index (PNM: 19.4 ± 3.9 vs ENM: 19.9 ± 4.4 vs NM: 19.9 ± 3.9 vs LM: 20.0 ± 3.8, %, P = .87) between the groups. In the physical function evaluation, there was no significant difference between the groups in grip strength (PNM: 19.8 ± 0.6 vs ENM: 20.3 ± 0.4 vs NM: 20.6 ± 0.2 vs LM: 20.6 ± 0.4, kg, P = .53). However, in the TUG (PNM: 11.8 ± 0.4 vs ENM: 10.3 ± 0.3 vs NM: 10.6 ± 0.1 vs LM: 10.2 ± 0.3, seconds, P < .01) and SPPB (PNM: 10.0 ± 0.2 vs ENM: 10.5 ± 0.2 vs NM: 10.6 ± 0.1 vs LM: 10.8 ± 0.2, points, P < .05), the PNM group showed significantly lower values than the other groups did. There was no difference in physical function between the groups except the PNM.

Premature natural menopause did not affect the body composition in elderly women but was associated with physical function deterioration. Therefore, more attention should be paid to the prevention of the physical function deterioration caused by premature natural menopause in elderly women.
Prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune inflammation index in acute ischemic stroke
Authors: Li Li-Hua , Chen Chung-Ting , Chang Yun-Chin , Chen Ying-Ju , Lee I-Hui , How Chorng-Kuang
Published: June 2021

The acute ischemic stroke (AIS) is a devastating disease and remains the leading cause of death and disability. This study aims to evaluate the role of hematological inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and systemic immune inflammation index [SII]) in predicting the neurological recovery in acute cerebrovascular events over 1-year follow-up.

Adult patients diagnosed with AIS within 3 hours from January 2016 to December 2018 were recruited retrospectively. The modified Rankin Scale (mRS) was recorded upon admission to the emergency department (ED) and 1, 3, 6, and 12 months after a stroke. The primary outcome measure was the neurological recovery. The neurological recovery was defined as an improvement in mRS score ≥ 1 compared with that at the ED admission baseline.

A total of 277 consecutive adult patients with AIS within 3 hours were enrolled. The initial average of the National Institute of Health Stroke Scale was 9.2 ± 7.8, and 90.3% of patients had an mRS ≥ 2 at ED admission baseline. The overall neurological recovery rates of 48.7%, 53.7%, 59.2%, and 55.9% were observed at 1, 3, 6, and 12 months follow-up, respectively. The multivariate analysis revealed that the baseline NLR value was a significant predictor of neurological recovery at 3 months after a stroke (adjusted odds ratio = 0.89, 95% confidence interval = 0.80–0.99, P = .035).

A low NLR at ED admission could be useful marker for predicting neurological recovery at 3 months after stroke.
Ventricular tachycardia of right ventricular outflow tract origin during the perioperative period
Authors: Park Ki Hyun , Lim Hyun Kyoung , Kim Na Eun , Shinn Helen Ki , Baek Yong Soo
Published: June 2021

Rationale:

Idiopathic ventricular tachycardia (VT) occurs in individuals without structural abnormalities in the heart, accounts for approximately 10% of total VTs. Furthermore, approximately 70% of idiopathic VTs originate from Right ventricular outflow tract (RVOT). However, among perioperative arrhythmias, incidence of VT after surgery is extremely rare and most arrhythmias are atrial origin.

Patient concerns:

A 69-year-old man with permanent pacemaker underwent colon surgery.

Diagnoses:

Patient suffered from low blood pressure and dizziness, sweating at post anesthetic care unit (PACU) and heart rate (HR) increased suddenly to 200 beats/min with monomorphic VT after bolus ephedrine administration and continuous dopamine infusion.

Interventions:

Pacemaker interrogation followed by DC cardioversion was done.

Outcomes:

Patient's vital signs became normal and symptoms are subsided.

Lessons:

RVOT VT can be caused by triggering activities, such as ephedrine, dopamine, and inadequate fluid management. These triggering activities are initiated by acceleration of HR from ventricles with infusion of catecholamine which lead monomorphic VT originating from RVOT.

RVOT origin PVCs can be precipitated into monomorphic VT by administrating catecholamines such as ephedrine and dopamine even in patient with pacemaker. The mechanism of these VTs includes catecholamine induced acceleration of HR. Since RVOT PVCs can be recognize by 12 EKGs, we should be pay more attentions to the pre-operation EKG and be cautious using catecholamines.
One-year clinical outcome after full-endoscopic interlaminar lumbar discectomy for isthmic lumbar spondylolisthesis
Authors: Kaneko Takeshi , Takano Yuichi , Inanami Hirohiko
Published: June 2021

Rationale:

For isthmic lumbar spondylolisthesis (ILS) associated with the removal of herniation, it remains challenging to perform less invasive and minimally disruptive procedures. Good results could potentially be obtained by further preserving the posterior elements in full-endoscopic lumbar discectomy (FESS), which is less invasive than microenscopic surgery (MES).

Patient concerns:

One patient complained of left leg pain, and another patient complained of right leg pain and low back pain.

Diagnoses:

Two patients with ILS and Meyerding Grade 1 lumbar spondylolisthesis.

Interventions:

We performed a full-endoscopic lumbar discectomy via the interlaminar space (FESS-IL) for L5/S1 lumbar disc herniation (LDH) accompanied by isthmic lumbar spondylolisthesis. FESS-IL was performed in 2 patients with radiculopathy caused by different types of LDH using a full endoscopic system with a 4.1 mm working channel and 6.9 mm outer diameter. A 3.5-mm diameter high-speed drill was used in one patient for an upward-migrated LDH in the inner-rim of the infravertebral border. The other patient underwent minimal resection without bone resection.

Outcomes:

The one-year clinical outcome included confirmation of pain relief and evacuation of migrated LDH on magnetic resonance imaging in all patients. There was no progression of slippage on radiography. The mean operative time was 82 min, and no complication was observed. The one-year clinical outcome demonstrated sufficient pain relief.

Lessons: The 1-y

ear postoperative outcome showed improvement. We believe that FESS-IL is a viable alternative operative approach for LDH for ILS.
Next-generation sequencing in thyroid cancers: do targetable alterations lead to a therapeutic advantage?
Authors: Moore Assaf , Bar Yael , Maurice-Dror Corinne , Finkel Inbar , Goldvaser Hadar , Dudnik Elizabeth , Goldstein Daniel A. , Gordon Noa , Billan Salem , Gutfeld Orit , Wolf Ido , Popovtzer Aron
Published: June 2021

Radioiodine-refractory thyroid cancers (IRTCs) are uncommon and have a poor prognosis. Treatment options for radioiodine-refractory and anaplastic tumors (ATCs) are limited. Although the genomic landscape of thyroid cancer has been studied, there is little evidence on whether next-generation sequencing (NGS) findings translate to tumor control.

We analyzed all patients with IRTC and ATC who underwent commercially available NGS in 3 cancer centers.

Twenty-two patients were identified, 16 patients with IRTCs and 6 patients with ATCs. Eighteen (82%) had targetable findings in NGS, nine patients were treated accordingly. Median progression-free survival for targeted treatment was 50 months [95% confidence interval (CI95%) 9.8–66.6] and2 months (CI95% 0.2–16.5) for IRTC and ATC, respectively. Of 4 patients who achieved durable responses of 7 to 50 months, 2 are ongoing. The estimated median OS of IRTC receiving targeted treatment was not reached (CI95% 89.7–111.4 months) and was 77.8 months (CI95% 52.5–114.6) for patients treated conventionally (P = .3).

NGS may detect clinically significant genetic alterations and benefit patients with advanced thyroid cancers.
Comparing plastic surgery and otolaryngology surgical outcomes and cartilage graft preferences in pediatric rhinoplasty
Authors: Doval Andres F. , Ourian Ariel , Boochoon Kieran S. , Chegireddy Vishwanath , Lypka Michael A. , Echo Anthony
Published: June 2021

Rhinoplasty in children has raised concerns about its safety in the pediatric population. There is scarcity of evidence describing outcomes and surgical techniques performed in pediatric rhinoplasty. We analyzed post-operative complications and cartilage preferences between plastic surgeons and otolaryngologists.

Data was collected through the Pediatric National Surgical Improvement Program from 2012 to 2017. Current Procedure Terminology codes were used for data extraction. Patients were grouped according to type of rhinoplasty procedures (primary, secondary, and cleft rhinoplasty). A comparison between plastic surgeons and otolaryngologists was made in each group in terms of postoperative complications. Additionally, a sub-group analysis based on cartilage graft preferences was performed.

During the study period, a total of 1839 patients underwent rhinoplasty procedures; plastic surgeons performed 1438 (78.2%) cases and otolaryngologists performed 401 (21.8%) cases. After analyzing each group, no significant differences were noted in terms of wound dehiscence, surgical site infection, readmission, or reoperation. Subgroup analysis revealed that plastic surgeons prefer using rib and ear cartilage, while otolaryngologists prefer septal and ear cartilage.

The analysis of 1839 pediatric patients undergoing three types of rhinoplasty procedures showed similar postoperative outcomes, but different cartilage graft utilization between plastic surgeons and otolaryngologists.