bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational burnout in oncologists in Kazakhstan
Authors: Vinnikov D , Romanova Z , Ussatayeva G , Tulekov Z , Dushimova Z , Khussainova I , Dushpanova A
Published: July 2021

Background

Although burnout levels in oncologists are likely high, its predictors remain poorly understood.

Aims

This study was aimed to verify the prevalence of occupational burnout in oncology doctors and nurses in the major cancer centre in Kazakhstan and to elucidate its predictors to plan future prevention activities.

Methods

In the leading tertiary-level cancer centre in Kazakhstan, we recruited 256 subjects (67% doctors and 33% nurses, 62% women, median age 37.5 [interquartile range 15] years) and offered them Maslach Burnout Inventory to quantify emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA). Demographics, fatigue, health-related quality of life with SF-8 and lifestyle were tested as predictors of burnout in multivariate logistic regression models.

Results

Number of subjects with high EE was 121 (47%), high DP was 161 (63%) and high PA was 152 (59%). Fatigue, worse mental component score (MCS), being single and not exercising regularly predicted more burnout in EE. Fatigue, worse physical component score (PCS) and worse MCS predicted more burnout in DP. Finally, more burnout in PA was independently associated with fatigue, worse PCS, being married or divorced and having a university or academic degree.

Conclusions

The prevalence of occupational burnout in oncologists was high, necessitating early burnout prevention programmes, addressing, among other, fatigue reduction and regular exercise.
Capitalism, laws, and the need for trustworthy institutions
Authors: Admati Anat R
Published: July 2021

Debates on capitalism get muddled by blind spots about essential institutions, particularly effective governments and legal systems that enable corporations to exist in their current form and markets to succeed at scale. Across regimes, incentives to maximize profits and power play key roles in determining outcomes, and all institutions are vulnerable to distortions from imbalances in control, information, and expertise. The key problems with capitalism today boil down to failed governance and confusions that obscure the issues and prevent beneficial changes. In recent decades, the forces of ‘free-market capitalism’ have undermined and overwhelmed democratic institutions, leading to intertwined crises in both capitalism and democracy. Deception and the manipulation of beliefs often distort both markets and political systems. The financial system illustrates starkly how key institutions have failed society and how flawed narratives enable recklessness and bad rules to persist. Fixing capitalism must start with seeing the challenges for what they are. The devil is then in the details of improving transparency, norms, rules, and civic engagement so as to prevent the abuse of power and to create more trustworthy and less corruptible versions of capitalism.
The global capital market reconsidered
Authors: Obstfeld Maurice
Published: July 2021

While the globalization of production has been a prominent target of anti-globalization backlash, globalized finance has seemed to be much less in the public bull’s-eye. The blueprint for the post-war international economy agreed at Bretton Woods in 1944 envisioned nothing like today’s extensive and fluid global capital market. The demise of the 1946–73 fixed exchange rate system, however, also brought a progressive dismantling of barriers to international financial flows motivated by special-interest politics, national economic competition, and ideology—alongside the benign desire for a more efficient international allocation of capital. Unfortunately, free cross-border financial capital mobility can compromise governments’ capacities to attain domestic economic and social goals in several ways. This essay links the dynamics of financial liberalization to the Teflon-like resilience of finance to backlash so far, and suggests that stronger backlash could emerge if national governments fail to enhance multilateral cooperation to manage the financial commons.
A comparison of vitamin D and cathelicidin (LL-37) levels between patients with active TB and their healthy contacts in a high HIV prevalence setting: a prospective descriptive study
Authors: Lungu Patrick Saili , Kilembe William , Lakhi Shabir , Sukwa Thomas , Njelesani Evarist , Zumla Alimuddin I , Mwaba Peter
Published: July 2021

Background

Studies from Asia and Europe indicate an association between vitamin D deficiency and susceptibility to TB. We performed an observational case-control study to determine vitamin D and cathelicidin (LL-37) levels and their association with active TB in newly diagnosed and microbiologically confirmed adult TB patients in Zambia, a high HIV prevalence setting.

Methods

Both total vitamin D and LL-37 were measured using ELISA from serum and supernatant isolated from cultured whole blood that was stimulated with heat-killed Mycobacterium tuberculosis. Statistical analysis was performed using STATA statistical software version 12.

Results

The median vitamin D in TB patients and healthy contacts was 28.7 (19.88–38.64) and 40.8 (31.2–49.44) ng/ml, respectively (p<0.001). The median LL-37 in TB patients compared with healthy contacts was 1.87 (2.74–8.93) and 6.73 (5.6–9.58) ng/ml, respectively (p=0.0149). Vitamin D correlation with LL-37 in healthy contacts was R2=0.7 (95% CI 0.566 to 0.944), p<0.0001. Normal vitamin D significantly predicted a healthy status (OR 4.06, p=0.002).

Conclusions

Significantly lower levels of vitamin D and LL-37 are seen in adults with newly diagnosed active TB. Longitudinal studies across various geographical regions are required to accurately define the roles of vitamin D and LL-37 in preventive and TB treatment outcomes.
Virulence Diversity of Phakopsora pachyrhizi in Mexico
Authors: García-Rodríguez Julio César , Vicente-Hernández Zeferino , Grajales-Solís Manuel , Yamanaka Naoki
Published: July 2021

Asian soybean rust, caused by the pathogen Phakopsora pachyrhizi, is the main soybean disease in Mexico and worldwide, threatening its production. Knowledge about the virulence of Mexican rust populations (MRPs) is crucial to develop or introduce soybean cultivars with resistance to this disease. This study investigated the geographic variation in the virulence of 19 MRPs collected in two states of Mexico (Tamaulipas and Chiapas) using a set of 12 differential soybean varieties. The inoculation of MRPs showed that there was no large difference in virulence to differentials carrying Rpp4 or Rpp5 between MRPs from the two states. However, a contrasting phenotype was observed on Rpp1, Rpp1-b, Rpp2, and Rpp3. In the comparative analysis of virulence profiles with 157 and 20 P. pachyrhizi samples from South America and Asia, respectively, the MRPs from Chiapas form an isolated cluster, including the Tamaulipas state. The MRPs from Tamaulipas clustered with South American samples because of common characteristics, such as virulence to Rpp1 and avirulence to Rpp1-b. However, opposite reactions on Rpp1 and Rpp1-b that have been reported in major U.S. pathogens were also observed in Chiapas samples. A common trend between Chiapas and major U.S. pathogens was also observed in Rpp3. The main conclusion of the present study is that the 1,000-km distance between these two states in Mexico makes a big difference in the virulence of Asian soybean rust.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Associations of opioid prescription dose and discontinuation with risk of substance-related morbidity in long-term opioid therapy
Authors: Quinn Patrick D. , Chang Zheng , Bair Matthew J. , Rickert Martin E. , Gibbons Robert D. , Kroenke Kurt , D'Onofrio Brian M.
Published: July 2021

Efforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. This study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194,839 adolescents and adults who initiated opioid prescription in 2010 to 2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17,582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose diagnoses. Relative to initial treatment, risk was greater within individual during subsequent periods of >60 to 120 (adjusted odds ratio [OR], 1.29; 95% CI, 1.12 to 1.49) and >120 (OR, 1.48; 95% CI, 1.24-1.76) daily morphine milligram equivalents. Risk was also greater during days 1 to 30 after discontinuations than during initial treatment (OR, 1.19; 95% CI, 1.05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.
#WhyIDidntReport
Authors: Guidry Jeanine P. D. , Sawyer Ashlee N. , Carlyle Kellie E. , Burton Candace W.
Published: July 2021

Background

In September 2018, Dr. Christine Blasey Ford accused then-nominee to the U.S. Supreme Court Brett Kavanaugh of sexual assault. When then-U.S. President Donald Trump questioned her credibility on Twitter, sexual assault survivors began tweeting their reasons for not reporting using the hashtag #WhyIDidntReport. This study examined how these posts were discussed on Twitter and to what extent the tweets fit within levels of the Social Ecological Model (SEM).

Method

This study used quantitative content analysis to code 1,000 tweets with #WhyIDidntReport for violence type, reasons for not reporting, and SEM levels.

Results

Overall, 68.7% of posts mentioned a specific reason for not reporting; of these, 24.1% referred to the perpetrator being in a position of power, 36.3% feared not being believed, and 20.6% mentioned that others invalidated the assault. In addition, 47.6% mentioned a specific form of violence. Within the SEM, 47.6% referred to individual, 52.6% to relational, 43.2% to community, and 21.7% to societal reasons for not reporting.

Conclusion

Reading social media content allows healthcare providers to directly discover how survivors talk about their experiences, priorities in the care environment, and how to support a patient-centered and trauma-informed approach.

Implications

Understanding reasons people do not report sexual assault is critical for healthcare professionals to engage patients in open, honest screening and intervention efforts.
Association of Organizational Factors With the Proportion of Healthy Behaviours and Control of Blood Pressure at a Company Level
Authors: Nagata Masako , Nagata Tomohisa , Takahashi Hirosuke , Mori Koji
Published: July 2021

Objectives:

The study examined a relationship between organizational factors and the health outcomes (health behaviors and blood pressure control) at a company level.

Methods:

This cross-sectional study using data from listed corporations on a stock exchange with 1000 to 30,000 employees that completed the health and productivity management survey of Japan in 2019.

Results:

We analyzed 886 companies. The presence of occupational health staff was associated with good health behaviors (no smoking and healthy body mass index) and good control of blood pressure. Implementation of education for manager was associated with low smoking rates.

Conclusion:

The implementation of organizational factors by corporations may improve the lifestyle behaviors and disease management of their employees.
Time to a Negative SARS-CoV-2 PCR Predicts Delayed Return to Work After Medical Leave in COVID-19 Infected Health Care Workers
Authors: Villarreal Jaime , Nieto Sandra Valeria , Vázquez Fabián , del Campo M. Teresa , Mahillo Ignacio , de la Hoz Rafael E.
Published: July 2021

Objective:

To investigate whether HCWs return to work (RTW) after COVID-19 was associated with time to a negative viral detection test.

Methods:

To evaluate the association of RTW with an undetectable RT-PCR adjusting for different factors.

Results:

Three hundred seventy-five HCWs who required medical leave for COVID-19 at a hospital in Madrid. Multivariable analyses confirmed the association of delayed RTW with interval to negative PCR (ORadj 1.12, 95% CI 1.08, 1.17) as well as age, sex, and nursing staff and clinical support services compared to physicians. A predictive model based on those variables is proposed, which had an area under the receiver operating curve of 0.82.

Conclusions:

Delayed RTW was associated with longer interval to a negative RT-PCR after symptom onset, adjusting for occupational category, age, and sex.
Association of Long Working Hours With Marital Status Changes in South Korea
Authors: Kim Hyunil , Lee Woncheol , Lee Yesung
Published: July 2021

Objective:

This study investigated the relationship between long working hours and the incidence of divorce or separation among Korean female and male workers.

Methods:

A cohort study was conducted in 125,108 Korean workers, married at baseline, who attended health examinations between 2012 and 2017 and had been followed annually or biennially until December 31, 2018. The weekly working hours and marital status changes were measured using self-administered questionnaires. This study was performed using sex stratification.

Results:

In a multivariable-adjusted model, by comparing working hours—>52 hours/week with 35 to 40 hours/week—the hazard ratios (95% confidence intervals) for incidents of divorce or separation were 1.60 (1.03–2.49) and 0.86 (0.66–1.12) in females and males, respectively.

Conclusions:

This study showed that long working hours could contribute to marital status changes in Korean female workers.
Thymoma Staging: An Analysis of the Different Schemas
Authors: Moran Cesar A.
Published: July 2021

Over the last years, a number of changes has taken place in the evaluation of thymomas. More recently, the introduction of a TNM staging system in the assessment of thymic epithelial tumors, in general, has been put forward. Important to highlight is that this TNM system is not based on tumor size, and because of that shortcoming, it was in need to borrow most if not all of the information from the experience derived from other schemas that over the years have been tested with larger series of cases. Also important to recognize is that this TNM system is nothing new as previous authors in the past had already attempted to provide a TNM system for thymomas without much success. Therefore, it becomes important that those involved with the staging of thymomas become familiar with previous schemas as the TNM system provides a slight different spin in the T component, while the M component truly represents advance stages of previous schemas. More importantly is to also highlight that despite the specific anatomic structures addressed in the T or M assessment, there is little information in the most important aspect of any staging system—clear definitions of invasion and metastasis and the gross assessment of these tumors to provide an accurate staging. Capsular integrity still remains paramount in such assessment. A critical assessment of TNM system compared with previously proposed staging systems and whether there is a real advancement in applying it is discussed as well as the gross assessment of these tumors to highlight the importance of the staging protocol.
Adverse Events Associated With Electromyogram Endotracheal Tubes in Thyroid and Parathyroid Surgery
Authors: Pier Matthew M. , Pasick Luke J. , Benito Daniel A. , Nogues Juan , Thakkar Punam , Joshi Arjun S. , Goodman Joseph F.
Published: July 2021

Objective

Thyroid and parathyroid surgeries are frequently performed with the aid of electromyogram endotracheal tubes. However, the most common adverse events have not been reported comprehensively. This study aimed to summarize the device adverse events, patient complications, and subsequent interventions related to electromyogram endotracheal tubes.

Methods

In this retrospective cross-sectional analysis, the US Food and Drug Administration’s Manufacturer and User Facility Device Experience database was queried for electromyogram endotracheal tube adverse events between 2010 and 2020. Data were extracted for devices used in thyroid and parathyroid surgery.

Results

Of 198 included reports, the most common device-related adverse events were loss of response to nerve stimulation (34.8%), cuff perforation (18.2%), and tube lumen obstruction (13.6%). Of 98 patient complications, the most common included ventilation failure (n = 50), airway trauma (n = 22), and recurrent laryngeal nerve injury (n = 5). There was 1 periprocedural death reported. Reported interventions include reintubation performed in 60.1% of all device adverse events, extended hospitalization in 27.3% of airway trauma events, and 5 tracheostomies performed for ventilation failure events. Forty-one events resulted in case delays and 13 events led to aborted cases. The most reported adverse events occurred in 2018 (n = 35) and 2015 (n = 30).

Conclusions

The most commonly reported adverse events associated with electromyogram endotracheal tubes include loss of response to nerve stimulation, cuff perforation, ventilation failure, and airway trauma. Subsequent interventions include reintubation, tracheostomy, extended hospitalization, and aborted cases. Surgical teams should consider these adverse events when consenting patients and using these devices in thyroid and parathyroid cases.
Effects of Text Enhancement on Reduction of Look-Alike Drug Name Confusion: A Systematic Review and Meta-analysis
Authors: Wang Hailiang , Tao Da , Yan Mian
Published: July 2021

Background and Objectives:

Drug name confusion induced by look-alike drug names represents a serious health care management problem in practice. Text enhancement by changing visual attributes of look-alike drug names has been proposed and widely applied in practice to mitigate drug name confusion. However, the effectiveness of text enhancement on reducing drug name confusion is yet to be determined. This study aimed to explore the effects of text enhancement on reduction of confusion caused by look-alike drug names through systematic review and meta-analysis.

Methods:

We searched 5 databases (from database inception to January 2020) for empirical studies that examined the effects of text enhancement on reduction of look-alike drug name–induced drug name confusion. The pooled outcome data were analyzed using either meta-analysis or a narrative synthesis approach.

Results:

From the 351 identified articles, 11 articles representing 20 individual trials were included. Five basic text enhancement methods were revealed, including Tall Man, red, boldface, contrast, and size enhancement, from which 4 Tall Man variants and 6 text enhancement combinations were derived. The meta-analysis results showed significant reduction in omission errors when using Tall Man (standardized mean difference [SMD] = −0.628, 95% confidence interval [CI]: −1.018 to −0.238, P = .002), red (SMD = −0.516, 95% CI: −1.002 to −0.030, P = .038), boldface (SMD = −1.027, 95% CI: −1.240 to −0.814, P < .001), and contrast (SMD = −0.437, 95% CI: −0.869 to −0.004, P = 0.048), as compared with lowercase. This finding was also supported in our subgroup analysis by task type for name differentiation tasks. No other significant effects of text enhancement were found for either commission errors or response time.

Conclusions:

Using Tall Man, red, boldface, or contrast could help reduce omission errors (ie, wrong medication selection) caused by look-alike drug names, particularly in name differentiation tasks. However, no text enhancement could shorten name search and/or differentiation time. Our findings could facilitate the understanding of the effects of text enhancement in the prevention of confusion errors caused by look-alike drug names and promote the application of text enhancement in practice.
Online Reviews of Hemodialysis Centers Correlate With Medicare and Medicaid Survey Measures of Patient Experience
Authors: Sadda Praneeth , Huang Brendan , Taha Birra
Published: July 2021

Background and Objectives:

Patient experience in outpatient hemodialysis has been shown to be significantly correlated with health outcomes. The current gold standard for assessing patient experience in outpatient hemodialysis is the In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH-CAHPS). Online reviews of outpatient hemodialysis centers could potentially serve as an additional source of information regarding patient experience, but they have not been well validated. This study aims to determine whether overall scores and subscores from patient-authored online reviews of outpatient dialysis centers are correlated with current gold standard survey-based measures of patient experience in outpatient hemodialysis.

Methods:

All reviews of hemodialysis centers posted to the online review site CiteHealth.com between March 2008 and October 2019 were collected (1081 reviews of 762 centers). Publicly-available ICH-CAHPS survey summary data and End Stage Renal Disease Quality Incentive Program (ESRD QIP) summary data from May 2016 to October 2019 were obtained from the Dialysis Facility Compare website. Spearman correlation coefficients were calculated between facilities' mean online review overall scores and subscores within a given year and their ICH-CAHPS ratings from the same year. Statistical significance was assessed with a 2-tailed permutation test. A Bonferroni correction for multiple hypothesis testing was applied.

Results:

The mean “Overall” score from CiteHealth.com had a significant positive correlation with the “Center Care Quality,” “Staff,” and “Facility” scores from ICH-CAHPS surveys. No significant correlation could be found between the mean “Overall” CiteHealth.com score and any other ICH-CAHPS patient satisfaction metric. There was a significant positive correlation between the mean CiteHealth.com “Center” score and the ICH-CAHPS “Center Care Quality” score, the mean CiteHealth.com “Facility” score and the ICH-CAHPS “Facility” score, and the mean CiteHealth.com “Staff” score and the ICH-CAHPS “Staff” score. No significant correlation was found between the mean CiteHealth.com “Nephrologist” score and the ICH-CAHPS “Nephrologist” score. No significant correlation was found between online review scores and ESRD QIP health outcome measures.

Conclusion:

Certain components of online reviews are significantly correlated with ICH-CAHPS measures of patient experience. Additionally, online reviews come with narrative comments that can offer specific insights into positive and negative aspects of patient care that cannot always be elucidated by numeric survey questions. Online reviews may have utility as an adjunctive source of information to patient experience surveys such as the ICH-CAHPS.
ICTV Virus Taxonomy Profile: Thaspiviridae 2021
Authors: Kim Jong-Geol , Gazi Khaled S. , Krupovic Mart , Rhee Sung-Keun ,   ICTV Report Consortium
Published: July 2021

Members of the family Thaspiviridae have linear dsDNA genomes of 27 to 29 kbp and are the first viruses known to infect mesophilic ammonia-oxidizing archaea of the phylum Thaumarchaeota. The spindle-shaped virions of Nitrosopumilus spindle-shaped virus 1 possess short tails at one pole and measure 64±3 nm in diameter and 112±6 nm in length. This morphology is similar to that of members of the families Fuselloviridae and Halspiviridae. Virus replication is not lytic but leads to growth inhibition of the host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Thaspiviridae, which is available at ictv.global/report/thaspiviridae.
Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introduction
Authors: Senghore Madikay , Tientcheu Peggy-Estelle , Worwui Archibald Kwame , Jarju Sheikh , Okoi Catherine , Suso Sambou M. S. , Foster-Nyarko Ebenezer , Ebruke Chinelo , Sonko Mohamadou , Kourna Mamdou Hama , Agossou Joseph , Tsolenyanu Enyonam , Renner Lorna Awo , Ansong Daniel , Sanneh Bakary , Cisse Catherine Boni , Boula Angeline , Miwanda Berthe , Lo Stephanie W. , Gladstone Rebecca A. , Schwartz Stephanie , Hawkins Paulina , McGee Lesley , Klugman Keith P. , Breiman Robert F. , Bentley Stephen D. , Mwenda Jason M. , Kwambana-Adams Brenda Anna , Antonio Martin
Published: July 2021

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of

Streptococcus pneumoniae

which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 

S

.

pneumoniae

isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.
Examining risk factors for weight change during midlife: A Mendelian randomization study
Authors: Power Grace M. , Tyrrell Jessica , Gkatzionis Apostolos , Fang Si , Heron Jon , Davey Smith George , Richardson Tom G.
Published: July 2021

Background

Maintaining a healthy weight across adulthood reduces morbidity and mortality risk in later life. This study aimed to examine factors contributing to weight change over a one-year interval in midlife. While conventional epidemiological analyses have reported risk factors associated with weight change, biases such as confounding present challenges when inferring causality.

Methods

Conventional observational analyses were used in addition to a one-sample Mendelian randomization (MR) approach to estimate the genetically predicted effects of four exposures (alcohol consumption, smoking intensity, educational attainment and Alzheimer’s disease liability) on weight change (mean age: 56.9 years) using data from 329 531 participants in the UK Biobank.

Results

One-sample MR indicated strong evidence that Alzheimer’s disease liability increased the odds of weight loss whilst conventional analyses reported little evidence of this. In MR and conventional epidemiological analyses, higher educational attainment was associated with maintaining a steady weight. In addition, higher alcohol consumption was associated with weight gain in conventional analyses only. Finally, whilst conventional analyses showed that smoking heaviness was associated with weight gain, the converse was supported by MR, which indicated strong evidence that smoking heaviness reduced the odds of weight gain.

Conclusions

Our findings highlight important risk factors for weight change in midlife and emphasise the public health importance of evaluating the dynamic changes to body weight within a causal inference setting.
Assessing the Utility of Low Resolution Brain Imaging: Treatment of Infant Hydrocephalus
Authors: Harper Joshua R. , Cherukuri Venkateswararao , O’Reilly Tom , Yu Mingzhao , Mbabazi-Kabachelor Edith , Mulando Ronald , Sheth Kevin N. , Webb Andrew G. , Warf Benjamin C. , Kulkarni Abhaya V. , Monga Vishal , Schiff Steven J.
Published: July 2021

As low-field MRI technology is being disseminated into clinical settings around the world, it is important to assess the image quality required to properly diagnose and treat a given disease and evaluate the role of machine learning algorithms, such as deep learning, in the enhancement of lower quality images. In this post-hoc analysis of an ongoing randomized clinical trial, we assessed the diagnostic utility of reduced-quality and deep learning enhanced images for hydrocephalus treatment planning. CT images of post-infectious infant hydrocephalus were degraded in terms of spatial resolution, noise, and contrast between brain and CSF and enhanced using deep learning algorithms. Both degraded and enhanced images were presented to three experienced pediatric neurosurgeons accustomed to working in low- to middle-income countries (LMIC) for assessment of clinical utility in treatment planning for hydrocephalus. In addition, enhanced images were presented alongside their ground-truth CT counterparts in order to assess whether reconstruction errors caused by the deep learning enhancement routine were acceptable to the evaluators. Results indicate that image resolution and contrast-to-noise ratio between brain and CSF predict the likelihood of an image being characterized as useful for hydrocephalus treatment planning. Deep learning enhancement substantially increases contrast-to-noise ratio improving the apparent likelihood of the image being useful; however, deep learning enhancement introduces structural errors which create a substantial risk of misleading clinical interpretation. We find that images with lower quality than is customarily acceptable can be useful for hydrocephalus treatment planning. Moreover, low quality images may be preferable to images enhanced with deep learning, since they do not introduce the risk of misleading information which could misguide treatment decisions. These findings advocate for new standards in assessing acceptable image quality for clinical use.
regentrans: a framework and R package for using genomics to study regional pathogen transmission
Authors: Hoffman Sophie , Lapp Zena , Wang Joyce , Snitkin Evan S
Published: July 2021

Increasing evidence of regional pathogen transmission networks highlights the importance of investigating the dissemination of multidrug-resistant organisms (MDROs) across a region to identify where transmission is occurring and how pathogens move across regions. We developed a framework for investigating MDRO regional transmission dynamics using whole-genome sequencing data and created regentrans, an easy-to-use, open source R package that implements these methods (https://github.com/Snitkin-Lab-Umich/regentrans). Using a dataset of over 400 carbapenem-resistant Klebsiella pneumoniae isolates collected from patients in 21 long-term acute care hospitals over a one-year period, we demonstrate how to use our framework to gain insights into differences in inter- and intra-facility transmission across different facilities and over time. This framework and corresponding R package will allow investigators to better understand the origins and transmission patterns of MDROs, which is the first step in understanding how to stop transmission at the regional level.

Impact statement

Increasing evidence suggests that pathogen transmission occurs across healthcare facilities. Genomic epidemiologic investigations into regional transmission shed light on potential drivers of regional prevalence and can inform coordinated interventions across healthcare facilities to reduce transmission. Here we present a framework for studying regional pathogen transmission using whole-genome sequencing data, and a corresponding open-source R package, regentrans, that implements these methods to streamline analyses and make them more accessible to other researchers and public health practitioners. We also discuss how these methods can be extended to study transmission in other settings.

Data summary

The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

The regentrans R package can be downloaded from GitHub: https://github.com/Snitkin-Lab-Umich/regentrans/

The manuscript figures are generated from regentrans example data and can also be found on GitHub: https://github.com/Snitkin-Lab-Umich/regentrans/tree/master/vignettes/manuscript_figures

The example data used in the package and manuscript is from BioProject accession no. PRJNA415194. The specific SRA accession numbers can be found in supplementary file S1. The metadata corresponding to these sequences can be found on the SRA Run Selector (isolate column) and as example data in the regentrans package.

The KPNIH1 sequence was used as the reference genome (SRA accession number SRZ080789)
Genome-wide characterization of Salmonella Typhimurium genes required for the fitness under iron restriction
Authors: Karash Sardar , Jiang Tieshan , Kwon Young Min
Published: July 2021

Iron is a crucial element for bacterial survival and virulence. During Salmonella infection, the host utilizes a variety of mechanisms to starve the pathogen from iron. However, Salmonella activates distinctive defense mechanisms to acquire iron and survive in iron-restricted host environments. Yet, the comprehensive set of the conditionally essential genes that underpin Salmonella survival under iron-restricted niches have not been fully explored. Here, we employed transposon sequencing (Tn-seq) method for high-resolution elucidation of the genes in Salmonella Typhimurium (S. Typhimurium) 14028s strain required for the growth under the in vitro conditions with 4 different levels of iron restriction achieved by iron chelator 2,2′-Dipyridine (Dip): mild (100 and 250), moderate (250) and severe iron restriction (400 μM). We found that the fitness of the mutants reduced significantly for 28 genes, suggesting the importance of these genes for the growth under iron restriction. These genes include sufABCDSE, iron transport fepD, siderophore tonB, sigma factor E ropE, phosphate transport pstAB, and zinc exporter zntA. The siderophore gene tonB was required in mild and moderate iron-restricted conditions, but they became dispensable in severe iron-restricted conditions. Remarkably, rpoE was required in moderate and severe iron restrictions, leading to complete attenuation of the mutant under these conditions. We also identified 30 genes for which the deletion of the genes resulted in increased fitness under iron-restricted conditions. The findings broaden our knowledge of how S. Typhimurium survives in iron-deficient environments, which could be utilized for the development of new therapeutic strategies targeting the pathways vital for iron metabolism, trafficking, and scavenging.
Microbiome structure of a wildDrosophilacommunity along tropical elevational gradients and comparison to laboratory lines
Authors: Brown Joel J. , Jandová Anna , Jeffs Christopher T. , Higgie Megan , Nováková Eva , Lewis Owen T. , Hrček Jan
Published: July 2021

Variation along environmental gradients in host-associated microbial communities is not well understood, compared to free-living microbial communities. Because elevational gradients may serve as natural proxies for climate change, understanding patterns along these gradients can inform our understanding of the threats hosts and their symbiotic microbes face in a warming world. In this study, we analysed bacterial microbiomes from pupae and adults of fourDrosophilaspecies native to Australian tropical rainforests. We sampled wild individuals at high and low elevation along two mountain gradients, to determine natural diversity patterns. Further, we sampled laboratory-reared individuals from isofemale lines established from the same localities, to see if any natural patterns are retained in the lab. In both environments, we controlled for diet to help elucidate other deterministic patterns of microbiome composition. We found small but significant differences inDrosophilabacterial community composition across elevation, with some notable taxonomic differences between differentDrosophilaspecies and sites. Further, we found that field-collected fly pupae had significantly richer microbiomes than laboratory-reared pupae. We also found similar microbiome composition in both types of provided diet, suggesting that the significant differences found amongDrosophilamicrobiomes are the product of surrounding environments with different bacterial species pools, possibly bound to elevational differences in temperature. Our results suggest that comparative studies between lab and field specimens help reveal the true variability in microbiome communities that can exist within a single species.

Importance

Bacteria form microbial communities inside most higher-level organisms, but we know little about how the microbiome varies along environmental gradients and between natural host populations and laboratory colonies. To explore such effects on insect-associated microbiomes, we studied gut microbiome in fourDrosophilaspecies over two mountain gradients in tropical Australia. We also compared these data to individuals kept in the laboratory to understand how different settings changed microbiome communities. We found that field sampled individuals had significantly higher microbiome diversity than those from the lab. In wildDrosophilapopulations, elevation explains a small but significant amount of the variation in their microbial communities. Our study highlights the importance of environmental bacterial sources forDrosophilamicrobiome composition across elevational gradients, and shows how comparative studies help reveal the true flexibility in microbiome communities that can exist within a species.
Crocosphaeraas a major consumer of fixed nitrogen despite its capability of nitrogen fixation
Authors: Masuda Takako , Inomura Keisuke , Kodama Taketoshi , Shiozaki Takuhei , Kitajima Satoshi , Armin Gabrielle , Matsui Takato , Suzuki Koji , Takeda Shigenobu , Prášil Ondřej , Furuya Ken
Published: July 2021

Crocosphaera watsonii(hereafterCrocosphaera) is a key nitrogen (N) fixer in the ocean, but its ability to consume combined N sources is still unclear. Usingin situmicrocosm incubations with an ecological model, we show thatCrocosphaerahas high competitive capability both under low and moderately high combined N concentrations. In field incubations,Crocosphaeraaccounted for the highest consumption of ammonium and nitrate, followed by pico-eukaryotes. The model analysis shows that cells have a high ammonium uptake rate (∼7 mol N (mol N)-1d-1at the maximum), which allows them to compete against pico-eukaryotes and non-diazotrophic cyanobacteria when combined N is sufficiently available. Even when combined N is depleted, their capability of nitrogen fixation allows higher growth rates compared to potential competitors. These results suggest the high fitness ofCrocosphaerain combined N limiting, oligotrophic oceans, and thus heightens its potential significance in its ecosystem and in biogeochemical cycling.
CDKs-mediated phosphorylation of PNKP is required for end-processing of single-strand DNA gaps on Okazaki Fragments and genome stability
Authors: Tsukada Kaima , Miyake Tomoko , Imamura Rikiya , Saikawa Kotaro , Saito Mizuki , Kase Naoya , Ishiai Masamichi , Matsumoto Yoshihisa , Shimada Mikio
Published: July 2021

Polynucleotide kinase phosphatase (PNKP) has enzymatic activities as 3′ -phosphatase and 5′ - kinase of DNA ends to promote DNA ligation and repair. Here, we show that cyclin-dependent kinases (CDKs) regulate the phosphorylation of threonine 118 (T118) in PNKP. This phosphorylation allows recruitment to the gapped DNA structure found in single-strand DNA nicks and/or gaps between Okazaki fragments (OFs) during DNA replication. T118A (alanine)-substituted PNKP-expressing cells exhibited accumulation of single-strand DNA gaps in S phase and accelerated replication fork progression. Furthermore, PNKP is involved in poly (ADP-ribose) polymerase 1 (PARP1)-dependent replication gap filling as a backup pathway in the absence of OFs ligation. Altogether, our data suggest that CDK-mediated PNKP phosphorylation at T118 is important for its recruitment to single-strand DNA gaps to proceed with OFs ligation and its backup errors via the gap-filling pathway to maintain genome stability.
Sleep spindle dynamics suggest over-consolidation in post-traumatic stress disorder
Authors: van der Heijden A.C. , Hofman W.F. , de Boer M. , Nijdam M.J. , van Marle H. J. F. , Jongedijk R. A. , Olff M. , Talamini L.M.
Published: July 2021

Devastating and persisting traumatic memories are a central symptom of post-traumatic stress disorder (PTSD). Sleep problems are highly co-occurrent with PTSD and intertwined with its etiology. Notably, sleep hosts memory consolidation processes, supported by sleep spindles (11-16 Hz). Here we assess the hypothesis that intrusive memory symptoms in PTSD may arise from excessive memory consolidation, reflected in exaggerated spindling. We use a newly developed spindle detection method, entailing minimal assumptions regarding spindle phenotype, to assess spindle activity in PTSD patients and traumatized controls (n=2×14, matched on gender). Our results show increased spindle activity in PTSD, which positively correlates with daytime intrusive memory symptoms. Together, these findings provide a putative mechanism through which profound sleep disturbance in PTSD may contribute to memory problems. Due to its uniform and unbiased approach, the new, minimal assumption spindle detection method seems a promising tool to detect aberrant spindling in psychiatric disorders.
High-amplitude network co-fluctuations linked to variation in hormone concentrations over menstrual cycle
Authors: Greenwell Sarah , Faskowitz Joshua , Pritschet Laura , Santander Tyler , Jacobs Emily G. , Betzel Richard F.
Published: July 2021

Many studies have shown that the human endocrine system modulates brain function, reporting associations between fluctuations in hormone concentrations and both brain activity and connectivity. However, how hormonal fluctuations impact fast changes in brain network structure over short timescales remains unknown. Here, we leverage “edge time series” analysis to investigate the relationship between high-amplitude network states and quotidian variation in sex steroid and gonadotropic hormones in a single individual sampled over the course of two endocrine states, across a natural menstrual cycle and under a hormonal regimen. We find that the frequency of high-amplitude network states are associated with follicle-stimulating and luteinizing hormone, but not the sex hormones estradiol and progesterone. Nevertheless, we show that scan-to-scan variation in the co-fluctuation patterns expressed during network states are robustly linked with the concentration of all four hormones, positing a network-level target of hormonal control. We conclude by speculating on the role of hormones in shaping ongoing brain dynamics.
Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing
Authors: Frey Nina , Tortola Luigi , Egli David , Janjuha Sharan , Marquart Kim Fabiano , Rothgangl Tanja , Ampenberger Franziska , Kopf Manfred , Schwank Gerald
Published: July 2021

Pancreatic ductal adenocarcinoma (PDA) is an inherently immune cell deprived tumor, characterized by desmoplastic stroma and suppressive immune cells. Here we systematically dissected PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening, and identified Rnf31 and Vps4b as essential factors required for escaping CD8+ T cell-killing. Using murine PDA cells and human PDA organoids, we demonstrate that Rnf31 protects from TNF-mediated caspase 8 cleavage and subsequent apoptosis induction. For Vps4b we found that inactivation impairs autophagy, resulting in increased accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis. Orthotopic transplantation of Rnf31− or Vps4b deficient pancreatic tumors, moreover, revealed increased CD8+ T cell infiltration and effector function, and markedly reduced tumor growth in mice. Our work uncovers vulnerabilities in PDA that might be exploited to render these tumors more susceptible to the immune system.
Dual Roles for Nuclear RNAi Argonautes in C. elegans Dosage Compensation
Authors: Davis Michael B. , Chawla Bahaar , Jash Eshna , Tushman Lillian E. , Haines Rebecca A. , Csankovszki Györgyi
Published: July 2021

Dosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in C. elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the Dosage Compensation Complex (DCC) which binds to both hermaphrodite X chromosomes and reduces transcriptional output by twofold. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probe and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3 exhibit de-repression of xol-1 transcripts, they also effect X chromosome condensation in a xol-1-independent manner. We also characterized the physiological contribution of Argonaute genes to dosage compensation using genetic assays and find that hrde-1 and nrde-3, together with the piRNA Argonaute prg-1, contribute to healthy dosage compensation both upstream and downstream of xol-1.