bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of multiple combined lifestyle interventions in reducing blood pressure among patients with prehypertension and hypertension: a network meta-analysis
Authors: Krishnamoorthy Yuvaraj , Nagarajan Ramya , Murali Sharan
Published: February 2022

Background

Different combinations of lifestyle interventions have been studied with varying results on hypertension control. Hence, this review was done to compare multiple combined lifestyle intervention in reducing blood pressure (BP) among patients with prehypertension or hypertension.

Methods

We conducted systematic search in the following databases: MEDLINE, PubMed Central, CENTRAL, ScienceDirect, Google Scholar from 1964 until November 2020. Estimates of comparative intervention effect from network meta-analyses (random-effects model) were represented as mean difference (MD) with 95% confidence interval.

Results

In total, 14 studies with 2451 participants were included. Almost all the studies had high risk of bias. Healthy diet (HD) and physical activity (PA) combination showed highest mean reduction in systolic BP (−9.88 mmHg) and diastolic BP (−6.28 mmHg) followed by HD + PA + smoking cessation + alcohol restriction combination (systolic BP = −6.58 mmHg, diastolic BP = −4.09 mmHg) compared with usual care. HD and PA combination had the highest probability of being the best intervention (82.8% for SBP and 81.7% for DBP).

Conclusion

We found that HD and PA are the most important combination of lifestyle modifications for prehypertensive and hypertensive patients. Hence, a coordinated approach is required from the clinicians by integrating beneficial effect of these modifications through education, counselling and support.

Summary Box

What is already known on this topic?

Various combinations of these multiple lifestyle interventions have been studied with varying results. Hence, it would be beneficial to find out the intervention combination with maximum effectiveness in controlling the blood pressure among prehypertensive or hypertensive patients.

What is added by this report?

We found that healthy diet and physical activity are the most important combination of lifestyle modifications required to achieve maximum reduction in SBP and DBP amongst HTN patients.

What are the implications for public health practice?

Our study has several implications for the clinicians and public health professionals. A coordinated approach is required from the clinicians by integrating the beneficial effect of these modifications through education, counselling and support. Public health professionals and policy makers should make use of these findings to design the policy, programme or scheme to tackle the burden of HTN or improve the control status amongst the established patients.
On the Effects of the Availability of Means of Payments: The Case of Uber
Authors: Alvarez Fernando , Argente David
Published: February 2022

We use three quasi-natural experiments in Mexico and one in Panama to estimate the effects of having the option to pay with cash on Uber rides. The ability to pay in cash affects the demand for rides, which is reflected in large changes in the total number of trips, fares, miles, and number of users after Uber introduced cash payments, particularly in lower-income city blocks. On the other hand, the effects on prices, estimated times of arrival, and competitor pricing are negligible, consistent with the supply of trips being very elastic. Although cash payments naturally increase the fraction of users that pay exclusively with cash, more than half of the users have access to both cards and cash, and alternate between payment methods. We find evidence consistent with cash and card payments being imperfectly substitutable at both the intensive and extensive margins, which magnifies the effect of policies that restrict the availability of payment methods.
Key Components for the Delivery of Cognitive Behavioral Therapies for Psychosis in Acute Psychiatric Inpatient Settings: A Delphi Study of Therapists’ Views
Authors: Wood Lisa , Jacobsen Pamela , Ovin Felicia , Morrison Anthony P
Published: February 2022

Cognitive Behavioral Therapy for psychosis (CBTp) is a psychological therapy recommended for people with psychosis which can start in the acute phase. However, there is not consensus on how CBTp should be delivered in an acute mental health inpatient setting. This study aimed to gain consensus from therapists on how CBTp should be delivered in this context. A 2-stage Delphi study was conducted to establish consensus on what the core components are of inpatient CBTp from the perspective of therapists who are experts in the field. Forty-five therapists took part in 2 rounds of rating statements on the areas of engagement and feedback, assessment and model, formulation, change strategies, homework, and principles and values. A final list of 114 statements were included, which were rated as essential or important by ≥80% of respondents. The delivery of inpatient CBTp is dependent on several adaptations to traditional CBTp including indirect work, being more flexible with session content and delivery, and making adaptations to the restrictive environment. These recommendations could inform training, competency frameworks, and delivery of CBTp in inpatient settings.
Neofusicoccum vaccinii: A Novel Species Causing Stem Blight and Dieback of Blueberries in China
Authors: Zhao Lin , Sun Wei , Zhao Lili , Zhang Lin , Yin Yueqi , Zhang Ying
Published: February 2022

Blueberries (Vaccinium spp.) have been considered to be a superfood because of their health benefits. Stem blight or dieback of blueberry has been frequently observed in commercial plantations, with incidences between 15 and 30% being observed in China. The causal agents of blueberry stem blight and dieback were surveyed at four commercial blueberry plantations in the Shandong, Fujian, Guizhou, and Yunnan Provinces of China during 2017 and 2019. Twenty-eight isolates of Neofusicoccum were obtained from 75 diseased and dead stem samples. Two taxa were identified. Of these, one novel species, Neofusicoccum vaccinii, was identified based on morphological characteristics and DNA sequence analysis of the concatenated internal transcribed spacer, the translation elongation factor-1α gene, and the beta-tubulin gene. Koch’s postulates tests indicated that N. vaccinii was pathogenic toward blueberry. N. parvum is the other species isolated in this study. The optimal temperature for mycelial growth was 30°C for both N. vaccinii and N. parvum. N. vaccinii, however, was more virulent than N. parvum in this study at temperatures ranging from 25 to 30°C. Coinoculation of N. vaccinii and N. parvum did not lead to increased disease severity. On the contrary, the aggressiveness of N. vaccinii was suppressed by the presence of N. parvum at 25 to 35°C.
Challenges and outcomes in airway management outside the operating room
Authors: Jarzebowski Mary , Estime Stephen , Russotto Vincenzo , Karamchandani Kunal
Published: February 2022

Purpose of review

Airway management outside the operating room poses unique challenges that every clinician should recognize. These include anatomic, physiologic, and logistic challenges, each of which can contribute to complications and lead to poor outcomes. Recognizing these challenges and highlighting known outcome data may better prepare the team, making this otherwise daunting procedure safer and potentially improving patient outcomes.

Recent findings

Newer intubating techniques and devices have made navigating anatomic airway challenges easier. However, physiological challenges during emergency airway management remain a cause of poor patient outcomes. Hemodynamic collapse has been identified as the most common peri-intubation adverse event and a leading cause of morbidity and mortality associated with the procedure.

Emergency airway management outside the operating room remains a high-risk procedure, associated with poor outcomes. Pre-intubation hemodynamic optimization may mitigate some of the risks, and future research should focus on identification of best strategies for hemodynamic optimization prior to and during this procedure.
The Effects of Dexmedetomidine on Perioperative Neurocognitive Outcomes After Noncardiac Surgery
Authors: Singh Amara , Broad Jeremy , Brenna Connor T. A. , Kaustov Lilia , Choi Stephen
Published: February 2022

Objective:

The purpose of this review is to examine the effect of dexmedetomidine on delayed neurocognitive recovery (dNCR; cognitive dysfunction ≥1 week postoperative) after major noncardiac surgery.

Background:

Dexmedetomidine (DEX) effectively reduces delirium in the intensive care unit and reportedly attenuates cognitive decline following major noncardiac surgery. Ascertaining the true effect on postoperative cognition is difficult because studies are limited by suboptimal selection of cognitive assessment tools, timing of testing, and criteria for defining significant cognitive decline

Methods:

Prospective randomized trials comparing perioperative DEX to placebo for major noncardiac surgery assessing cognitive function ≥1 week postoperative were included. Pediatric, nonhuman, and non-English trials, and those where executive function was not assessed were excluded. Data were abstracted by 3 reviewers independently and in parallel according to PRISMA guidelines. The a priori binary primary outcome is dNCR defined as cognitive function declining by the minimal clinically important difference or accepted alternate measure (eg, Reliable Change Index ≥1.96). Bias was assessed with the Cochrane Collaboration tool. Data were pooled using a random effects model.

Results:

Among 287 citations identified, 26 (9%) met criteria for full-text retrieval. Eleven randomized trials (1233 participants) were included for qualitative analysis, and 7 trials (616 participants) were included for meta-analysis of dNCR. Dexmedetomidine did not reduce the incidence of dNCR significantly (OR 0.57, 95% CI 0.30–1.10, P = 0.09) compared with placebo. There was no difference in the incidence of delirium (OR 0.94, 95% CI 0.55–1.63, P = 0.83) and a higher incidence of hemodynamic instability (OR 2.11, 95% CI 1.22–3.65, P = 0.008).

Conclusions:

Dexmedetomidine does not reduce dNCR 1 week after major noncardiac surgery. This meta-analysis does not yet support the use of perioperative DEX to improve short term cognitive outcomes at this time; trials underway may yet change this conclusion while larger trials are needed to refine the point estimate of effect and examine long-term cognitive outcomes.
Surgical treatment options for congenital pseudarthrosis of tibia in children: cross-union versus other options: a systematic review
Authors: Rastogi Anuj , Agarwal Anil
Published: February 2022

The systematic review aimed to provide a comprehensive update on various surgical treatment options for congenital pseudarthrosis of tibia (CPT) in children and the outcome achieved in terms of union, union time and complications of non-union and refracture. A literature search was performed in PubMed (including Medline) database for broad keywords: ‘Congenital pseudarthrosis of tibia and children’. Studies selected included full-text articles on surgical treatments of CPT following: intra-medullary rod (IMR)/Ilizarov/combined IMR with Ilizarov/vascularized fibular graft (VFG) and cross-union. Out of 719 studies, 57(1227 CPT patients/1235 tibias) were included for review. Cross-union group had 100% union rate with no non-unions, least refracture rate (22.5%) and minimal time to primary union (4.5 months). For IMR, Ilizarov, combined IMR with Ilizarov and VFG, the respective results were as follows: primary union rates – 67.7, 84.2, 83.7 and 65.3%; final union – 76.5, 81.5, 92.4 and 87.1%; primary union time – 12.6, 9.3, 5.3 and 9.5 months; non-union rates – 17.0, 13.6, 6.0 and 7.9%; refracture rates – 48.1, 47.7, 33.7 and 34.6%. The success probability was lowest for IMR (35.2%), 44% for Ilizarov, 55.5% for combined IMR with Ilizarov, 42.7% for VFG and highest 77.5% for cross-union group. Outcomes of the more recent cross-union technique fare better than other surgical methods. However, studies on cross-union are few and longer follow-up is lacking. Combined IMR with Ilizarov and VFG have better results compared to IMR or Ilizarov alone.
Review of 20 Years of Continuous Quality Improvement of a Rapid Response System, at Four Institutions, to Identify Key Process Responsible for Its Success
Authors: Vandegrift Mary Anne , Granata Robert , Totten Vicken Y. , Kellett John , Sebat Frank
Published: February 2022

BACKGROUND:

Rapid response systems are still in development, and their practices vary significantly from hospital to hospital. Although the literature supports their value and a four-arm structure, it is unclear within these arms (efferent, afferent, quality assurance, administrative arms) which processes and procedures are responsible for their efficacy. This article reports the evolution of a rapid response system over many years at four institutions and considers the key elements that likely contribute to its efficacy.

METHODS:

Retrospective evaluation of the processes, procedures, and outcomes of an adult general-ward rapid response system as it evolved, at four nonaffiliated community medical centers, spanning 2 decades of development and refinement. System and patient outcomes examined included the number of rapid response system activations/1,000 admissions, time to rapid response system activation and/or interventions, cardiac arrest rate, and/or hospital mortality over time.

RESULTS:

In the three hospitals that collected control and intervention data, there was significant increase in earlier and total number of rapid response system activations, more rapid administration of protocolized interventions, and associated decreases in cardiac arrest rate and hospital mortality of the respective population. In all four institutions three important common rapid response system processes were identified: early identification of at-risk patient using a novel focused bedside-assessment tool, leading to classification of the pathophysiologic process, linked to goal-directed intervention protocols.

CONCLUSIONS:

Our review of a rapid response system that evolved over 20 years across four unrelated institutions revealed a common care pathway that coupled a focused bedside at-risk patient assessment leading to pathophysiologic classification of the patients decline linked to goal-directed intervention protocols. We speculate that the improved outcomes observed are a consequence of effective implementation and coupling of these three processes, as they are important in identifying and treating early the signs of tissue hypoxia and hypoperfusion, which remain the basic pathophysiologic threats of acute deterioration.
Effects of Sedatives on Sleep Architecture Measured With Odds Ratio Product in Critically Ill Patients
Authors: Georgopoulos Dimitris , Kondili Eumorfia , Alexopoulou Christina , Younes Magdy
Published: February 2022

OBJECTIVES:

Evaluation of sleep quality in critically ill patients is difficult using conventional scoring criteria. The aim of this study was to examine sleep in critically ill patients with and without light sedation using the odds ratio product, a validated continuous metric of sleep depth (0 = deep sleep; 2.5 = full wakefulness) that does not rely on the features needed for conventional staging.

DESIGN:

Retrospective study.

SETTINGS:

A 16-bed medical-surgical ICU.

PATIENTS:

Twenty-three mechanically ventilated patients who had previously undergone two nocturnal sleep studies, one without and one with sedation (propofol, n = 12; dexmedetomidine, n = 11).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Sleep architecture was evaluated with odds ratio product analysis by the distribution of 30-second epochs with different odds ratio product values. Electroencephalogram spectral patterns and frequency of wake intrusions (3-s odds ratio product > 1.75) were measured at different odds ratio product levels. Thirty-seven normal sleepers were used as controls. Compared with normal sleepers, unsedated critically ill patients spent little time in stable sleep (percent odds ratio product < 1.0: 31% vs 63%; p < 0.001), whereas most of the time were either in stage wake (odds ratio product > 1.75) or in a transitional state (odds ratio product 1.0–1.75), characterized by frequent wake intrusions. Propofol and dexmedetomidine had comparable effects on sleep. Sedation resulted in significant shift in odds ratio product distribution toward normal; percent odds ratio product less than 1.0 increased by 54% (p = 0.006), and percent odds ratio product greater than 1.75 decreased by 48% (p = 0.013). In six patients (26%), sedation failed to improve sleep.

CONCLUSIONS:

In stable critically ill unsedated patients, sleep quality is poor with frequent wake intrusions and little stable sleep. Light sedation with propofol or dexmedetomidine resulted in a shift in sleep architecture toward normal in most, but not all, patients.
Legionella Pneumonia in the ICU: A Tertiary Care Center Experience Over 10 Years
Authors: Andrea Luke , Dicpinigaitis Peter V. , Fazzari Melissa J. , Kapoor Sumit
Published: February 2022

OBJECTIVES:

Few studies have reported the complications and outcomes of patients with Legionella pneumonia requiring ICU admission. The objective of our study is to report the clinical course, complications, and 30-day mortality of patients with Legionella pneumonia admitted to the critical care units at our medical center over a 10-year period.

DESIGN:

Retrospective observational study.

SETTING:

Tertiary care teaching hospital.

PATIENTS:

All adult (≥ 18 yr old) patients with Legionella pneumonia admitted to the ICUs from January 1, 2010, to December 31, 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 88 patients with Legionella pneumonia were admitted to ICUs over the 10-year period. The majority of infections (n = 80; 90.9%) were community acquired. The median (interquartile range) age of patients was 60 years (51.5–71.0 yr); 58 (66%) were male, and 41 (46.6%) identified their race as Black. The median (interquartile range) Sequential Organ Failure Assessment score at ICU admission was 6 (3–9). The distribution of infections showed seasonal dominance with most cases (86%) occurring in the summer to early fall (May to October). Invasive mechanical ventilation was required in 62 patients (70.5%), septic shock developed in 57 patients (64.8%), and acute respiratory distress syndrome developed in 42 patients (47.7%). A majority of patients developed acute kidney injury (n = 69; 78.4%), with 15 (21.7%) receiving only intermittent hemodialysis and 15 (21.7%) requiring continuous renal replacement therapy. Ten patients required venovenous extracorporeal membrane oxygenation support; eight (80%) survived and were successfully decannulated. Overall 30-day mortality was 26.1% (n = 23). Advanced age, higher Sequential Organ Failure Assessment score at admission, and not receiving Legionella-specific antimicrobial therapy within 24 hours of hospital admission were predictors of 30-day mortality.

CONCLUSIONS:

Patients with Legionella pneumonia may require ICU admission and major organ support. Legionella-targeted antibiotics should be included in the empiric regimen for any patient with severe pneumonia. Outcomes of extracorporeal membrane oxygenation therapy in this population are encouraging.
The EXIMIOUS project—Mapping exposure-induced immune effects: connecting the exposome and the immunome
Authors: Ronsmans Steven , Hougaard Karin Sørig , Nawrot Tim S. , Plusquin Michelle , Huaux François , Cruz María Jesús , Moldovan Horatiu , Verpaele Steven , Jayapala Murali , Tunney Michael , Humblet-Baron Stéphanie , Dirven Hubert , Nygaard Unni Cecilie , Lindeman Birgitte , Duale Nur , Liston Adrian , Flachs Esben Meulengracht , Kastaniegaard Kenneth , Ketzel Matthias , Goetz Julia , Vanoirbeek Jeroen , Ghosh Manosij , Hoet Peter H. M. ,   The EXIMIOUS Consortium
Published: February 2022

Immune-mediated, noncommunicable diseases—such as autoimmune and inflammatory diseases—are chronic disorders, in which the interaction between environmental exposures and the immune system plays an important role. The prevalence and societal costs of these diseases are rising in the European Union. The EXIMIOUS consortium—gathering experts in immunology, toxicology, occupational health, clinical medicine, exposure science, epidemiology, bioinformatics, and sensor development—will study eleven European study populations, covering the entire lifespan, including prenatal life. Innovative ways of characterizing and quantifying the exposome will be combined with high-dimensional immunophenotyping and -profiling platforms to map the immune effects (immunome) induced by the exposome. We will use two main approaches that “meet in the middle”—one starting from the exposome, the other starting from health effects. Novel bioinformatics tools, based on systems immunology and machine learning, will be used to integrate and analyze these large datasets to identify immune fingerprints that reflect a person’s lifetime exposome or that are early predictors of disease. This will allow researchers, policymakers, and clinicians to grasp the impact of the exposome on the immune system at the level of individuals and populations.
Toward a better measure of midlife sexual function: pooled analyses in nearly 1,000 women participating in MsFLASH randomized trials
Authors: Reed Susan D. , Carpenter Janet S. , Larson Joseph , Mitchell Caroline M. , Shifren Jan , Heiman Julia , Woods Nancy Fugate , Lindau Stacy Tessler , LaCroix Andrea Z. , Guthrie Katherine A.
Published: February 2022

Objective:

Evaluate appropriateness of the current Female Sexual Function Index (FSFI)-19 value of <26.6 to designate female sexual dysfunction (FSD) in postmenopausal women, using the Female Sexual Distress-Revised (FSDS-R) scale to measure distress.

Methods:

Participant-level data containing standardized measures from five completed Menopause Strategies: Finding Lasting Answers for Symptoms and Health trials was pooled. Baseline characteristics and FSFI-19 scores were compared across trials (F-test, homogeneity). FSFI-19 score associations with the FSDS-R were described. Receiver operating characteristic (ROC) curves were plotted to illustrate the choice of optimal FSFI-19 value to predict sexual distress. ROC curves were also estimated adjusting for trial number, clinical center, age, education, race, smoking, and BMI.

Results:

Nine hundred ninety eight women (79.2% postmenopausal), mean age 55.9 (SD 4.8) had complete FSFI-19, FSDS-R, and covariate data. Baseline mean FSFI-19 score among all participants and sexually active participants was 18.7 (SD 9.5) and 22.0 (SD 7.2), respectively. There was a consistent pattern across the trials of inverse association between poorer sexual function (FSFI-19) and greater sexual distress. Based on the ROC curve showing the likelihood of FSDS-R frequent or greater distress according to cut points of FSFI, the optimal cut point for FSD was FSFI-19 <21 for all participants. This cut point corresponded to sensitivity 87.2% (95% CI, 83.4-91.0), specificity 57.9% (95% CI, 54.3-61.6) and adjusted area under the ROC curve 78.8% (95% CI, 75.8-81.8).

Conclusions:

A new FSFI-19 cut point of ≥21 should be considered to describe normal sexual function in periand postmenopausal women as opposed to the standard cut point of >26.6.

Video Summary:

http://links.lww.com/MENO/A915.
Different regimens of menopausal hormone therapy for improving sleep quality: a systematic review and meta-analysis
Authors: Pan Zhuo , Wen Shu , Qiao Xiaoyong , Yang Meina , Shen Xiaoyang , Xu Liangzhi
Published: February 2022

Importance:

Long-term sleep disturbances in menopausal women are closely related to cardiovascular disorders, metabolic disorders, and cognitive impairment. At present, hormone therapy (HT) is a standard treatment for menopausal symptoms. However, it remains unclear whether HT can improve sleep quality.

Objective:

We did a systematic review and meta-analysis to assess the effects of different HT regimens on menopausal sleep quality.

Evidence Review:

We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, and Web of Science for randomized controlled trials of menopausal HT on sleep disturbances up to June 14,2021. Information about ongoing and unpublished trials was collected by searching WHOICTRP and ClinicalTrials.gov. Our primary outcome was sleep quality with objective measurements. We estimated the standardized mean difference (SMD) using random-effects models.

Findings:

We identified a total of 3,059 studies and finally included 15 studies in the meta-analysis. Compared with placebo, HT improved self-reported sleep outcomes (SMD = –0.13; 95% CI, –0.18 to -0.08, P 
< 0.00001 and I
2 = 41%), but not sleep parameters measured by polysomnography. Subgroup analyses according to the regimen of HT showed that 17β-estradiol (17β-E2) (SMD = –0.34; 95% CI, –0.51 to -0.17, P 
< 0.0001, and I
2 = 0%) and conjugated equine estrogens (SMD = –0.10; 95% CI, −0.12 to −0.07, P 
< 0.00001, and I
2 = 0%) improved sleep quality. Moreover, transdermal administration (SMD = −0.35; 95% CI, −0.64 to −0.06, and P 
= 0.02) was more beneficial than oral (SMD = −0.10; 95% CI, −0.14 to −0.07, and P 
< 0.00001). In addition, the combination of estrogen and progesterone had a positive effect on sleep disturbance (SMD = −0.10; 95% CI, −0.13 to −0.07, P 
< 0.00001, and I
2 = 0%), while estrogen monotherapy did not. The results showed that estrogen/micronized progesterone (SMD = −0.22; 95% CI, −0.37 to −0.06, P = 0.007, and I
2 = 0%) and estrogen/medroxyprogesterone acetate (SMD = −0.10; 95% CI, −0.13 to −0.07, P 
< 0.00001, and I
2 = 0%) could alleviate sleep disturbance.

Conclusions and Relevance:

HT has a beneficial effect on sleep disturbance to some extent, and the formulations and routes of administration of hormonal agents influence the effect size.
Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature
Authors: Samur Bahadir M. , Gümüş Gülsüm , Canpolat Mehmet , Gümüş Hakan , Per Hüseyin , Cağlayan Ahmet Okay
Published: February 2022

Thiamine metabolism dysfunction syndrome-4 (THMD-4) is an autosomal recessive inherited rare disease (OMIM #613710) characterized by febrile illness associated episodic encephalopathy, leading to transient neurological dysfunction and progressive polyneuropathy. We report three patients from two different families with normal development, episodic encephalopathy, gait disorder, progressive chronic polyneuropathy characterized by motor difficulties, distal weakness, and hoarseness (dysphonia). We identified a homozygous missense c.576G>C, p.(Gln192His) variant in the SLC25A19 gene in both families by whole-exome sequencing. Following genetic diagnosis, thiamine replacement therapy was started, and improvement was observed in all affected patients. We highlight the associated phenotypes of an SCL25A19 mutation leading to clinical features of THMD-4.
COVID-19 and other respiratory tract infections at mass gathering religious and sporting events
Authors: Al-Tawfiq Jaffar A. , El-Kafrawy Sherif A. , McCloskey Brian , Azhar Esam I.
Published: February 2022

Purpose of review

Mass gathering (MG) religious events provide ideal conditions for transmission and globalization of respiratory tract infections (RTIs). We review recent literature on COVID-19 and other RTIs at recurring international annual MG religious and sporting events.

Recent findings

Due to the COVID-19 pandemic organizers of MG religious and sporting events introduced risk-based infection control measures that limited transmission of RTIs. The 2020 and 2021 Hajj were conducted with limited numbers of pilgrims compared to the annual millions of pilgrims. The Tokyo 2020 Olympic and Paralympic Games were cancelled and held in 2021. The success of the COVID-19 countermeasures at the 2021 Hajj and 2021 Tokyo Olympics was based on implementing good public health and social measures alongside a comprehensive testing strategy.

MG events are associated with transmission of a range of bacterial and viral RTIs. Introducing risk based a multitude of public health interventions can reduce transmission of SARS-CoV-2 and other RTIs.
Parent Experience of Communication about Children’s Surgery: A Qualitative Analysis
Authors: Claus Lauren E , Links Anne R , Amos Janine , DiCarlo Heather , Jelin Eric , Koka Rahul , Beach Mary Catherine , Boss Emily F.
Published: February 2022

Introduction:

Parent experience is a core component of the quality of pediatric care and an increasingly common focus of quality improvement initiatives. However, the parent experience of communication in the pediatric surgical setting remains unexplored.

Methods:

We conducted semi-structured interviews with 20 parents of children undergoing surgery. Interviews were analyzed using directed qualitative content analysis.

Results:

Content analysis revealed 3 overarching themes. The theme of “provider–parent communication” included interpersonal behaviors and communication-originating skills of the surgeon. Parents valued surgeons incorporating multimodal information-sharing techniques, recognizing children’s psychological needs, providing reassurance, engaging in teamwork, and including parents. The theme of “parental emotional experiences” included domains of parent worry, intimidation, offense, self-doubt, mistrust, and strength surrounding their child’s surgery. Parents felt simultaneously responsible for their child’s welfare and for understanding medical information. The theme of “process improvement” included preparation for surgery, efficiency, managing delays, anesthesia induction, emergence from anesthesia, privacy, and preparation for recovery.

Conclusions:

Themes identified through these parental narratives and proposed solutions inform quality improvement efforts related to surgeon communication strategies and facilitate family-centered surgical care for children. Parents often provided solutions after they described concerns, which attests to the utility of parent perspectives.
Cognitive Bias and Therapy Choice in Breast Reconstruction Surgery Decision-Making
Authors: Whyte Stephen , Bray Laura , Chan Ho Fai , Chan Raymond J. , Hunt Jeremy , Peltz Tim S. , Dulleck Uwe , Hutmacher Dietmar W.
Published: February 2022

Background:

Understanding how medical experts and their patients process and transfer information is of critical importance for efficient health care provision. Behavioral economics has explored similar credence markets where economic incentives, information asymmetry, and cognitive bias can impact patient and surgeon choice. The aim of the current study is to explore how framing and behavioral bias affect elective restorative surgery decision-making, such as breast reconstruction following cancer treatment.

Methods:

The authors’ study uses a cross-sectional survey data set of specialist surgeons (n = 53), breast care nurses (n = 101), and former or current breast cancer patients (n = 689). Data collected include participant demographics, medical history, a battery of cognitive bias tests, and a behavioral framing experiment.

Results:

This study finds statistically significant differences in breast reconstruction surgery preference by patients and nurses when decision options are framed in different ways (i.e., positively versus negatively). The authors’ analysis of surgeons, nurses, and patients shows no statistically significant difference across eight common forms of cognitive bias. Rather, the authors find that the behavioral biases are prevalent to the same extent in each group. This may indicate that differences in experience and education seem not to mitigate biases that may affect patient choices and medical professional’s recommendations. The authors’ multivariate analysis identifies patient age (p < 0.0001), body mass index, and self-perceived health (p < 0.05) as negative correlates for choice of implant-based reconstruction.

Conclusion:

For surgeons, nurses, and patients, the authors find uniform evidence of cognitive bias; more specifically, for patients and nurses, the authors find inconsistency in preference for type of surgical therapy chosen when alternative procedures are framed in different ways (i.e., framing bias).
Electronic Decision Support in the Delivery Room Using Augmented Reality to Improve Newborn Life Support Guideline Adherence
Authors: Tsang Kishan D. , Ottow Mendel K. , van Heijst Arno F. J. , Antonius Timothy A. J.
Published: February 2022

Introduction

The Newborn Life Support (NLS) guideline aims to provide healthcare professionals a consistent approach during neonatal resuscitation. Adherence to this and analogous guidelines has repetitively been proven to be difficult.

This study evaluates adherence to guideline using a novel augmented reality (Microsoft HoloLens) electronic decision support tool during standardized simulated neonatal resuscitation compared with subjects working from memory alone.

Methods

In this randomized controlled pilot study, 18 professionals responsible for neonatal resuscitation were randomized to the intervention group and 11 to the control group. Demographic characteristics were similar between both groups. A standardized neonatal resuscitation scenario was performed, which was recorded and later assessed for adherence to the NLS algorithm by 2 independent reviewers. Secondary outcomes were error classification in case of algorithm deviation and time to the execution or completion of critical steps in the algorithm to determine delay.

Results

Median (interquartile range) scores of a theoretical maximum of 40 in the intervention group were 34 (32.5–35.5) versus 29 (27–33) in the control group (P = 0.004). Errors of commission were committed less frequently with the electronic decision support tool 2 (1–2.5) compared with 4 (2–4) in the control group (P = 0.029). Analysis of time to initiation or completion of key steps in the NLS algorithm showed no significant differences between both groups.

Conclusions

Healthcare professionals using an electronic decision support tool showed improved adherence to the NLS guideline during simulated neonatal resuscitation.
Novel Association of Lyme disease, Age, and Atopic Dermatitis
Authors: Lee Brandon T. , Galloway Sarah D. , Feng Qingying , Strausz Satu , Shoham Maia , Hansen Paige , Torrez Dulgeroff Laughing Bear , Blacker Grace , Yiu Ying Y. , Mansfield Paul ,   FinnGen, Saleem Atif , Gars Eric , Sanders Erin C. , Weissman Irving L. , Ollila Hanna M. , Tal Michal Caspi
Published: February 2022

Borrelia burgdorferi(B. burgdorferi) is a bacterial spirochete that can cause Lyme disease after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific. The murine substrain, C3H/HeJ, is a frequently utilized mouse model of Lyme disease. In this study, we sought to investigate the correlation of age with onset and severity of dermatitis, both in mice infected withB. burgdorferias well as humans who have had a diagnosis of Lyme disease. Female C3H/HeJ mice aged 6-8 weeks, 1 year, or 2 years were infected intraperitoneally with 105B. burgdorferi. Dermatitis of the tail was evaluated by gross examination and histology. Additional female C3H/HeJ and C57BL/6J mice aged 5 weeks were injected intradermally with 105B. burgdorfericontaining the luciferase reporter gene then analyzed under in vivo imaging. Human data via electronic health records of 342,499 Finnish individuals was tested and analyzed for associations between Lyme disease and atopic dermatitis. Dermatitis worsened over the course of untreated infection, with ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. These features of dermatitis were present in infected mice after 1 year of age. We further confirm the presence ofB. burgdorferiin the tail through quantification of bioluminescence and immunohistochemistry of both C3H/HeJ and C57BL/6J mice. This relationship among Lyme disease, atopic dermatitis, and host age seen in the mouse model is consistent with a large pool (342,499) of human epidemiological data from Finland. We identified 5,248 individuals with Lyme disease and 17,233 with atopic dermatitis in FinnGen. Retrospective analysis shows Lyme disease is associated with atopic dermatitis (OR = 1.91 [1.68 -2.37],P< 2e-16). More visits due to Lyme disease complications (3 or more visits versus 1 visit) were associated with atopic dermatitis (OR = 2.19 [1.35-3.55],P= 0.0014) and risk of developing atopic dermatitis over time (HR=2.26 [1.54-3.95],P= 0.0017). Data from mice and humans reveal a novel relationship among Lyme disease, age, and atopic dermatitis. Through defined pathological scoring, we demonstrate the onset of murine atopic dermatitis withB. burgdorferiinfection, which is further exacerbated by host age at time of infection. In humans, a diagnosis of Lyme disease in FinnGen was associated with atopic dermatitis and further research is warranted to establish causation.
A nucleation barrier spring-loads the CBM signalosome for binary activation
Authors: Rodríguez Gama Alejandro , Miller Tayla , Lange Jeffrey J. , Unruh Jay , Halfmann Randal
Published: February 2022

Immune cells activate in a binary, switch-like fashion that involves proteins polymerizing into large complexes known as signalosomes. The switch-like nature of signalosome formation has been proposed to result from large energy barriers to polymer nucleation. Whether such nucleation barriers indeed drive binary immune responses has not yet been shown. Here, we employed an in-cell biophysical approach to dissect the assembly mechanism of the CARD-BCL10-MALT1 (CBM) signalosome, a key determinant of transcription factor NF-κB activation in both innate and adaptive immunity. We found that the adaptor protein BCL10 encodes an intrinsic nucleation barrier, and that this barrier has been conserved from cnidaria to humans. Using optogenetic tools and a single-cell transcriptional reporter of NF-κB activity, we further revealed that endogenous human BCL10 is supersaturated even in unstimulated cells, indicating that the nucleation barrier operationally stores energy for subsequent activation. We found that upon stimulation, BCL10 nucleation by CARD9 multimers triggers self-templated polymerization that saturates NF-κB activation to produce a binary response. Pathogenic mutants of CARD9 that cause human immunodeficiencies eliminated nucleating activity. Conversely, a hyperactive cancer-causing mutation in BCL10 increased its spontaneous nucleation. Our results indicate that unassembled CBM signalosome components function analogously to a spring-loaded mousetrap, constitutively poised to activate NF-κB through irrevocable polymerization. This finding may inform our understanding of the root causes and progressive nature of pathogenic and age-associated inflammation.
Deep learning of Protein Sequence Design of Protein-protein Interactions
Authors: Syrlybaeva Raulia , Strauch Eva-Maria
Published: February 2022

Motivation

As more data of experimentally determined protein structures is becoming available, data-driven models to describe protein sequence-structure relationship become more feasible. Within this space, the amino acid sequence design of protein-protein interactions has still been a rather challenging sub-problem with very low success rates - yet it is central for the most biological processes.

Results

We developed an attention-based deep learning model inspired by algorithms used for image-caption assignments for sequence design of peptides or protein fragments. These interaction fragments are derived from and represent core parts of protein-protein interfaces. Our trained model allows the one-sided design of a given protein fragment which can be applicable for the redesign of protein-interfaces or the de novo design of new interactions fragments. Here we demonstrate its potential by recapitulating naturally occurring protein-protein interactions including antibody-antigen complexes. The designed interfaces capture essential native interactions with high prediction accuracy and have native-like binding affinities. It further does not need precise backbone location, making it an attractive tool for working with de novo design of protein-protein interactions.

Availability

The source code of the method is available at https://github.com/strauchlab/iNNterfaceDesign

Supplementary information

Supplementary data are available at Bioinformatics online.
Neural correlates of perceived emotions in human insula and amygdala
Authors: Zhang Yang , Zhou Wenjing , Huang Juan , Hong Bo , Wang Xiaoqin
Published: February 2022

The emotional status of a speaker is an important non-linguistic cue carried by human voice and can be perceived by a listener in vocal communication. Understanding the neural circuits involved in processing emotions carried by human voice is crucial for understanding the neural basis of social interaction. Previous studies have shown that human insula and amygdala responded more selectively to emotional sounds than non-emotional sounds. However, it is not clear whether the neural selectivity to emotional sounds in these brain structures is determined by the emotion presented by a speaker or by the emotion perceived by a listener. In this study, we recorded intracranial electroencephalography (iEEG) responses to emotional human voices while subjects performed emotion recognition tasks. We found that the iEEG responses of Heschl’s gyrus (HG) and posterior insula were determined by the presented emotion, whereas the iEEG responses of anterior insula and amygdala were driven by the perceived emotion. These results suggest that the anterior insula and amygdala play a crucial role in representing subjectively perceived emotion.
Differences between Omicron SARS-CoV-2 RBD and other variants in their ability to interact with cell receptors and monoclonal antibodies
Authors: Giron Carolina Corrêa , Laaksonen Aatto , da Silva Fernando Luís Barroso
Published: February 2022

SARS-CoV-2 has caused immeasurable damage worldwide and available treatments with high efficacy are still scarce. With the continuous emergence of new variants of the virus, such as Omicron, Alpha, Beta, Gamma, and Delta - the so-called variants of concern, the available therapeutic and prevention strategies had to return to the experimental trial to verify their effectiveness against them. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). Special attention is given to the Omicron variant and its comparison with the others, including its sublineage BA.2 and two new ones (B.1.640.1 and B.1.640.2/IHU) recently found in France. By using constant-pH Monte Carlo simulations, the free energy of interactions between the SARS-CoV-2 receptor-binding domain (RBD) from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and several mAbs) were calculated. It was evaluated both the impact of mutations for the RBD-ACE2 and how strongly each of mAb can bind to the virus RBD, which can indicate their therapeutic potential for neutralization. RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms typically found in Europeans (rs142984500 and rs4646116), indicating that these types of polymorphisms may be related to genetic susceptibility to COVID-19. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 33 studied binders, groups of mAbs were identified with weak (e.g. S110 and Ab3b4), medium (e.g. CR3022), and strong binding affinities (e.g. P01’’’, S2K146 and S230). All the mAbs with strong binding capacity could also bind to the RBD from SARS-CoV-1, SARS-CoV-2 wt, and all studied variants. These mAbs and especially their combination are amenable to experimentation and clinical trials because of their high binding affinities and neutralization potential for current known virus mutations and a universal coronavirus.
The spatial periodic computation of hippocampus-entorhinal circuit in navigation
Authors: Zhang Bo , Liu Jia
Published: February 2022

Summary

To achieve the computational goal of navigating in both physical and mental spaces, human brain employs a cognitive map constructed by the global metrics of the entorhinal cortex and the local locations of the hippocampus. However, how these two regions work collaboratively in navigation remains unclear. Here, we designed an object-matching task where human participants unknowingly manipulated object variants arranged in a ring-like structure around a central prototype. Functional MRI revealed a 3-fold spatial periodicity of hippocampal activity, which tracked the navigation path from the original object variants to the central prototype in the object space. Importantly, this spatial periodicity of the hippocampus was phase-locked with the well-documented 6-fold periodicity of the entorhinal cortex, suggesting a periodic scaffold connecting these two regions. In addition, a 3-fold periodicity was found embedded in human behavior, which fluctuated as a function of the navigation path and phase-locked with hippocampal activity. Finally, we proposed an E-H PhaseSync model to illustrate that the spatial periodicity originated from the population activity of entorhinal grid cells may serve as a scaffold in the hippocampal- entorhinal network, where hippocampal vector fields emerge as the neural basis for utilizing the cognitive map in navigation.
An intranasal lentiviral booster broadens immune recognition of SARS-CoV-2 variants and reinforces the waning mRNA vaccine-induced immunity that it targets to lung mucosa
Authors: Vesin Benjamin , Lopez Jodie , Noirat Amandine , Authié Pierre , Fert Ingrid , Le Chevalier Fabien , Moncoq Fanny , Nemirov Kirill , Blanc Catherine , Planchais Cyril , Mouquet Hugo , Guinet Françoise , Hardy David , Gerke Christiane , Anna François , Bourgine Maryline , Majiessi Laleh , Charneau Pierre
Published: February 2022

As the COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, the adaptive immunity initially induced by the first-generation COVID-19 vaccines wains and needs to be strengthened and broadened in specificity. Vaccination by the nasal route induces mucosal humoral and cellular immunity at the entry point of SARS-CoV-2 into the host organism and has been shown to be the most effective for reducing viral transmission. The lentiviral vaccination vector (LV) is particularly suitable for this route of immunization because it is non-cytopathic, non-replicative and scarcely inflammatory. Here, to set up an optimized cross-protective intranasal booster against COVID-19, we generated an LV encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::SBeta-2P). mRNA vaccine–primed and -boosted mice, with waning primary humoral immunity at 4 months post-vaccination, were boosted intranasally with LV::SBeta-2P. Strong boost effect was detected on cross-sero-neutralizing activity and systemic T-cell immunity. In addition, mucosal anti-Spike IgG and IgA, lung resident B cells, and effector memory and resident T cells were efficiently induced, correlating with complete pulmonary protection against the SARS-CoV-2 Delta variant, demonstrating the suitability of the LV::SBeta-2P vaccine candidate as an intranasal booster against COVID-19.