bluuebunny/crossref_metadata_2025 huggingface dataset:
Gestational diabetes and other adverse pregnancy outcomes in polycystic ovary syndrome
Authors: Selen Daryl J. , Powe Camille E.
Published: August 2022

Purpose of review

This review provides an update on gestational diabetes (GDM) and other adverse pregnancy outcomes in individuals with polycystic ovary syndrome (PCOS), one of the most common metabolic disorders and causes of infertility.

Recent findings

Recent studies using Rotterdam diagnostic criteria for PCOS have supported prior literature suggesting that pregnant individuals with PCOS are at an increased risk of GDM. Risk factors for GDM in this population include overweight/obesity, insulin resistance, hyperandrogenism, amenorrhea, and history of miscarriage. It is possible that subtypes of PCOS (metabolic vs. lean/reproductive) pose differential risk. There are no current screening or treatment guidelines specifically for individuals with PCOS for GDM prevention. Although metformin has been studied for GDM prevention in PCOS, there has been no proven benefit. For infertility treatment, assisted reproductive technology and in-vitro fertilization do not appear to increase the risk of GDM in individuals with PCOS desiring pregnancy.

Recent studies of pregnant individuals with PCOS suggest an increased risk of adverse pregnancy outcomes, including GDM. Larger, prospective studies using standardized diagnostic criteria are warranted to determine if the risk is from PCOS generally, or if there are subtypes of PCOS (metabolic vs. lean/reproductive) at a higher risk of GDM than others.
The Impact of the COVID-19 Pandemic on Foreign Body Ingestion Trends in Children: A Comparison of the Pre-Pandemic Period to 2020
Authors: Geibel Elyse , Pasman Eric , Nylund Cade , Rudolph Bryan , Reeves Patrick
Published: August 2022

Foreign body ingestion (FBI) among children is associated with morbidity and mortality. We used the National Electronic Injury Surveillance System to compare FBI trends from 2017–2019 to 2020 during the spread of SARS-CoV-2. The pandemic and associated stay-at-home orders were associated with uptrends in button battery and magnet ingestions but unchanged total FBI trends.
Evaluation of the Nurse-Led Symptom Management Program for Patients With Gynecologic Cancer Undergoing Chemotherapy
Authors: Paşalak Şeyma İnciser , Selçukbiricik Fatih , Seven Memnun
Published: August 2022

Background

Patients with cancer experience symptoms concurrently. Nurses need to make multisymptom management and educate patients about self-management strategies.

Objective

The aim of this study was to evaluate the effect of a nurse-led symptom management program (NL-SMP), developed based on the Symptom Management Model, quality of life (QoL), and symptom severity of women with gynecological cancer undergoing chemotherapy.

Methods

This randomized controlled study sample consisted of 41 women receiving chemotherapy at an outpatient clinic in Istanbul, Turkey, between November 2018 and December 2019. European Organisation for Research and Treatment of Cancer Quality-of-Life Scale, Edmonton Symptom Assessment Scale, and Modified Brief Sexual Symptom Checklist-Women were used to collect data. Women were randomly assigned to 2 groups: intervention (n = 21) and control (n = 20). The intervention group attended the NL-SMP in addition to usual care. Data were collected at the first (time 1), third (time 2), and last chemotherapy cycle (time 3). Repeated measures analysis of variance, Cochran-Q, and t tests were used to analyze the data.

Results

In the intervention group, the QoL was significantly higher; symptom severity was lower than that of the control group at time 2 and time 3. At time 3, more women in the control group reported at least 1 sexual difficulty and were not satisfied with their sexual function, whereas there was no change for women in the intervention group.

Conclusion

The NL-SMP, which consisted of systematic symptom assessment, prioritization of symptoms, providing symptom, and patient-specific education, decreased deterioration in the QoL and symptom severity of women.

Implications for Practice

Conducting multisymptom assessments, prioritizing symptoms, providing symptom- and patient-specific education, and supporting symptom self-management throughout treatment can lead to effective symptom management.
Knowledge and Perceived Emotions Regarding an Anal Cancer Preventive Program in People Diagnosed With HIV
Authors: Diez-Martínez Marcos , Perpiñá-Galvañ Juana , Fernández-Alcántara Manuel , García-Rodríguez Gema , Carreres Melissa , Portilla Joaquín , Cabañero-Martínez María José
Published: August 2022

Background

To the best of our knowledge, no studies have yet examined the emotional repercussions of the care processes among people infected with the human immunodeficiency virus who participate in preventive anal cancer screening programs.

Objective

This study aimed to explore the knowledge, emotions, sexuality, barriers, and facilitators perceived by this patient group during the process of anal cancer screening and diagnosis.

Methods

Detailed, semistructured, qualitative interviews were completed with 17 men and 3 women to explore their knowledge, experiences, and emotions regarding the screening process. Purposive sampling was conducted on the basis of age, gender, and type of lesion diagnosed in the anal biopsy.

Results

Four major themes were identified: 1) knowledge of the disease and its treatment, 2) emotions perceived by the patients, 3) the influence of screening on sexual practices, and 4) facilitators and obstacles during the care provision process. Patients reported appropriate knowledge of anal cancer and human papillomavirus. Predominant emotions were worry and fear with avoidance as one of the coping strategies.

Conclusion

These results suggest that communication of information and clinical results can be improved.

Implication for Practice

Understanding the facilitators and barriers to the program will allow the integration of interventions designed to improve healthcare provision into direct care.
Increasing Supportive Care for Patients With COVID-19–Related Respiratory Deterioration in Non-ICU Settings
Authors: Stellpflug Courtney L. , Olson Stephanie D. , Balko Britta A. , Mrowka Victoria G. , Focht Gregory D. , Elmer Jennifer L.
Published: August 2022

Background:

Prepandemic hospital guidelines were unable to support an acute influx of patients with respiratory deterioration. New processes for general care practice were needed to facilitate patient care.

Purpose:

To develop and evaluate guidelines to safely treat patients with COVID-19 respiratory deterioration in the general care setting.

Methods:

A quality improvement project with 2 PDSA (Plan-Do-Study-Act) cycles was used to develop guidelines for high-flow oxygen and prone positioning, along with frequent monitoring and collaboration with virtual critical care support.

Results:

Over 6 months, 126 patients with COVID-19 were cared for on general care units. Zero intubations occurred on the general care units, with 211 patient hospital days spent in general care that previously would have required an intensive care unit bed.

Conclusions:

Patients in the general care setting with respiratory decline can safely be managed with appropriate monitoring criteria, oxygen device settings, and nursing support unitizing technology.
Fall Prevention With the Smart Socks System Reduces Hospital Fall Rates
Authors: Moore Tammy , Kline David , Palettas Marilly , Bodine Tina
Published: August 2022

Background:

Falls of inpatients are common in hospitals. Existing fall prevention measures do not work consistently.

Purpose:

To determine whether Smart Socks reduce fall rates in fall risk patients at a major academic health center's neurological and neurosurgical based units.

Methods:

A prospective study was conducted that provided fall risk patients with Smart Socks and no other fall prevention system. Data collected included duration of Smart Socks wearing, number of alarms, response times, and patient-days.

Results:

A total of 569 fall risk patients were included for 2211.6 patient-days. There were 4999 Smart Socks alarms, but none of the patients fell. We observed a lower fall rate, of 0 per 1000 patient-days, for patients wearing Smart Socks than the historical fall rate of 4 per 1000 patient-days. The median nurse response time was 24 seconds.

Conclusions:

The Smart Socks reduced fall rates of fall risk patients included in the study.
Linking Hospitals to Communities Through Evidence-Based Practice
Authors: Schutte Debra L. , Kisting Mary , Warren Chastity , Stoneman Miranda
Published: August 2022

Evidence-based practice (EBP) and innovation are critical to quality and improved outcomes in the acute care setting and are often driven by bedside caregiver and clinical nurse specialist collaboration. Several EBP models and frameworks exist to guide these efforts. Although existing models do not preclude external evidence and community-based stakeholders, they largely do not explicitly connect the hospital-based effort to the community either. In our experience in facilitating EBP projects within an acute care hospital in the upper Midwest, we observed multiple situations in which nurse-led EBP projects intersected with the surrounding community in multiple phases of the project. The purpose of this article is to demonstrate an explicit connection between hospital-placed EBP processes and community/population health. To illustrate this assertion, 3 exemplars of nurse-driven, hospital-placed innovation are presented. Implications for practice and research are discussed.
Efficiency and Safety of Electronic Health Records in Switzerland—A Comparative Analysis of 2 Commercial Systems in Hospitals
Authors: Fischer Simone , Schwappach David L. B.
Published: August 2022

Objectives

Differences in efficiency and safety between 2 electronic health record (systems A and B) in Swiss hospitals were investigated.

Methods

In a scenario-based usability test under experimental conditions, a total of 100 physicians at 4 hospitals were asked to complete typical routine tasks, like medication or imaging orders. Differences in number of mouse clicks and time-on-task as indicators of efficiency and error type, error count, and rate as indicators of patient safety between hospital sites were analyzed. Time-on-task and clicks were correlated with error count.

Results

There were differences in efficiency and safety between hospitals. Overall, physicians working with system B required less clicks (A: 511, B: 442, P = 0.001) and time (A: 2055 seconds, B: 1713 seconds, P = 0.055) and made fewer errors (A: 40%, B: 27%, P < 0.001). No participant completed all tasks correctly. The most frequent error in medication and radiology ordering was a wrong dose and a wrong level, respectively. Time errors were particularly prevalent in laboratory orders. Higher error counts coincided with longer time-on-task (r = 0.50, P < 0.001) and more clicks (r = 0.47, P < 0.001).

Conclusions

The variations in clicks, time, and errors are likely due to naive functionality and design of the systems and differences in their implementation. The high error rates coincide with inefficiency and jeopardize patient safety and produce economic costs and burden on physicians. The results raise usability concerns with potential for severe patient harm. A deeper understanding of differences as well as regulative guidelines and policy making are needed.
The Psychological Safety Scale of the Safety, Communication, Operational, Reliability, and Engagement (SCORE) Survey: A Brief, Diagnostic, and Actionable Metric for the Ability to Speak Up in Healthcare Settings
Authors: Adair Kathryn C. , Heath Annemarie , Frye Maureen A. , Frankel Allan , Proulx Joshua , Rehder Kyle J. , Eckert Erin , Penny Caitlin , Belz Franz , Sexton J. Bryan
Published: August 2022

Objectives

The current study aimed to guide the assessment and improvement of psychological safety (PS) by (1) examining the psychometric properties of a brief novel PS scale, (2) assessing relationships between PS and other safety culture domains, (3) exploring whether PS differs by healthcare worker demographic factors, and (4) exploring whether PS differs by participation in 2 institutional programs, which encourage PS and speaking-up with patient safety concerns (i.e., Safety WalkRounds and Positive Leadership WalkRounds).

Methods

Of 13,040 eligible healthcare workers across a large academic health system, 10,627 (response rate, 81%) completed the 6-item PS scale, demographics, safety culture scales, and questions on exposure to institutional initiatives. Psychometric analyses, correlations, analyses of variance, and t tests were used to test the properties of the PS scale and how it differs by demographic factors and exposure to PS-enhancing initiatives.

Results

The PS scale exhibited strong psychometric properties, and a 1-factor model fit the data well (Cronbach α = 0.80; root mean square error approximation = 0.08; Confirmatory Fit Index = 0.97; Tucker-Lewis Fit Index = 0.95). Psychological Safety scores differed significantly by role, shift, shift length, and years in specialty. The PS scale correlated significantly and in expected directions with safety culture scales. The PS score was significantly higher in work settings with higher rates of exposure to Safety WalkRounds or Positive Leadership WalkRounds.

Conclusions

The PS scale is brief, diagnostic, and actionable. It exhibits strong psychometric properties; is associated with better safety, teamwork climate, and well-being; differs by demographic factors; and is significantly higher for those who have been exposed to PS-enhancing initiatives.
The impact, effectiveness and outcomes of targeted screening thresholds for programmatic latent tuberculosis infection testing in HIV
Authors: White Helena A. , Baggaley Rebecca F. , Okhai Hajra , Patel Hemu , Stephenson Iain , Bodimeade Chris , Wiselka Martin J. , Pareek Manish
Published: August 2022

Background:

Screening and treatment for latent tuberculosis infection (LTBI) are key for TB control. In the UK, the National Institute for Health and Care Excellence (NICE) and the British HIV Association (BHIVA) give conflicting guidance on which groups of people with HIV (PWH) should be screened, and previous national analysis demonstrated heterogeneity in how guidance is applied. There is an urgent need for a firmer clinical effectiveness evidence base on which to build screening policy.

Methods:

We conducted a systematic, programmatic LTBI-screening intervention for all PWH receiving care in Leicester, UK. We compared yields (percentage IGRA positive) and number of tests required when applying the NICE and BHIVA testing strategies, as well as strategies targeting screening by TB incidence in patients’ countries of birth.

Results:

Of 1053 PWH tested, 118 were IGRA-positive (11.2%). Positivity was associated with higher TB incidence in country-of-birth [adjusted odds ratio, 50–149 cases compared with <50 cases/100 000: 11.6; 95% confidence interval (CI) 4.79–28.10)]. There was high testing uptake (1053/1069, 98.5%). Appropriate chemoprophylaxis was commenced in 100 of 117 (85.5%) patients diagnosed with LTBI, of whom 96 of 100 (96.0%) completed treatment. Delivering targeted testing to PWH from countries with TB incidence greater than 150 per 100 000 population or any sub-Saharan African country, would have correctly identified 89.8% of all LTBI cases while cutting tests required by 46.1% compared with NICE guidance, performing as well as BHIVA 2018 guidance.

Conclusion:

Targeting screening to higher risk PWH increases yield and reduces the number requiring testing. Our proposed ‘PWH-LTBI streamlined guidance’ offers a simplified approach, with the potential to improve national LTBI-screening implementation.
A Novel Technique for the Correction of Unilateral Craniofacial Fibrous Dysplasia Using Multiplanar Sequential Cutting Guides
Authors: Jain Rahul , Mahendru Sanjay , Khazanchi Rakesh K.
Published: August 2022

In this unique case report, the authors have described a new method for the correction of unilateral craniofacial fibrous dysplasia by using sequential cutting guides. Due to the complex 3-dimensional anatomy of zygoma, it needs to be chiseled in multiple planes to mimic the normal contralateral side. To achieve this, 3 different guides were used one after the other to perform osteotomies in different planes and remove the excess fibrous bone.
Providing a Purposeful and Stimulating Volunteer Opportunity for Older Adults With Mild Cognitive Impairment
Authors: Piette John D. , Roberts J. Scott , Marinec Nicolle , Chen Jenny , Yon Sarah , Maly Marianna , Swalwell Kathleen , Hampstead Benjamin
Published: August 2022

Social interactions have cognitive and emotional benefits for older adults with mild cognitive impairment (MCI). The prevalence of loneliness and isolation in this population has been repeatedly noted, but interventions remain limited. We designed a program to connect older adults with MCI with an engaging volunteering opportunity, through videoconferencing conversations with another adult practicing English (English language learner). Ten MCI-English language learner pairs had conversation sessions over 6 weeks. We tracked session engagement, monitored conversations, and interviewed participants at follow-up. Pairs completed 78% of scheduled sessions; only 7% were missed because the MCI participant canceled or failed to appear. Qualitative interviews suggested that participants felt comfortable and engaged. No negative experiences were observed or reported. This program is feasible and potentially desirable for older adults with MCI. This model is interesting given the concern about in-person volunteering risks, and the millions of people motivated to improve English fluency.
A systems approach to decipher a role of transcription factor RegX3 in the adaptation of Mycobacterium tuberculosis to hypoxic stress
Authors: Mahatha Amar Chandra , Banerjee Srijon Kaushik , Ghosh Abhirupa , Lata Suruchi , Saha Sudipto , Basu Joyoti , Kundu Manikuntala
Published: August 2022

Two-component systems (TCSs) are required for the ability of

Mycobacterium tuberculosis

to respond to stress. The paired TCS, SenX3-RegX3 is known to respond to phosphate starvation and acid stress. The other stress conditions under which RegX3 is required for

M. tuberculosis

to mount an appropriate response, remain incompletely understood. Here we have employed genome-wide microarray profiling to compare gene expression in a ΔregX3 mutant with the wild-type under phosphate stress, in order to gain information on the probable RegX3 regulon. We pulled out a set of 128 hypoxia-associated genes, which could potentially be regulated by RegX3, by overlapping the gene set downregulated at least twofold in ΔregX3 with the gene set reported in the literature to be associated with the response to hypoxia. We identified potential RegX3 binding inverted repeats at the loci of 41 of these genes, in silico. We also observed that ΔregX3 was attenuated in terms of its ability to withstand hypoxia, and this was reversed upon complementation with regX3, corroborating a role of RegX3 in the response of

M. tuberculosis

to hypoxia. We validated the binding of RegX3 at the upstream regions of a selected set of these genes. Electrophoretic mobility shift assays (EMSAs) confirmed that RegX3 binds to the upstream regions of the hypoxia-associated genes Rv3334, whiB7, Rv0195, Rv0196 and Rv1960c. Gene expression analyses showed that the expression of these genes is regulated by RegX3 under hypoxia. We also show that the expression of whiB7, Rv3334 and Rv0195 in macrophage-grown

M. tuberculosis

, is dependent on RegX3. Finally, we show that attenuation of survival of ΔregX3 under hypoxia is partly reversed upon overexpression of either Rv0195 or Rv3334, suggesting that the RegX3-Rv0195 and the RegX3-Rv3334 axis are involved in the adaptation of

M. tuberculosis

to a hypoxic environment.
A co-designed website (FindWays) to improve mental health literacy of parents of children with mental health problems: protocol for a pilot randomised controlled trial
Authors: Peyton Daniel , Wadley Greg , Hackworth Naomi , Grobler Anneke , Hiscock Harriet
Published: August 2022

Background

Mental health problems, such as behavioural and emotional problems, are prevalent in children. These problems can have long lasting, detrimental effects on the child, their parents and society. Most children with a mental health problem do not receive professional help. Those that do get help can face long wait times. While waiting, parents want to learn how they can help their child. To address this need, we co-designed a new website to help parents find ways of helping their child’s mental health problem while waiting to get specialist help.

Objectives

To assess the acceptability and feasibility of a new co-designed website, FindWays, through a pilot randomised controlled trial. The protocol is registered with ISRCTN (ISRCTN64605513).

Methods

This study will recruit up to 60 parents of children aged two-twelve years old referred to a paediatrician for behavioural and/or emotional problems. Participants will be randomly allocated by computer generated number sequence to either the intervention or control group. Intervention group participants will receive access to the FindWays website to help them manage their child’s mental health problem while they wait to see the paediatrician. Acceptability and feasibility will be assessed over the 4-month intervention through mixed methods including: recruitment, adherence, retention, net promoter score (quantitative measures) and semi-structured interviews to gain an in-depth understanding of parents’ experience and potential adverse effects (qualitative measure). Secondary outcomes measured by parent survey at 4-months post randomisation include child mental health, parent mental health, impact of the child’s mental health problem on their functioning and family, and health service use and associated costs.

Results

Recruitment commenced June 2022 with publication expected in October 2023.

Conclusion

This study will provide novel data on the acceptability and feasibility of a new website co-designed with parents to help them find ways of managing their child’s behaviour and emotions.

Ethics approval granted by The Royal Children’s Hospital Human Research Ethics Committee - HREC/75854/RCHM-2021 on 22/4/2022.
Ancestral lineage of SARS-CoV-2 is more stable in human biological fluids than Alpha, Beta and Omicron variants of concern
Authors: Kwon Taeyong , Gaudreault Natasha N. , Meekins David A. , McDowell Chester D. , Cool Konner , Richt Juergen A.
Published: August 2022

SARS-CoV-2 is a zoonotic virus which was first identified in 2019, and has quickly spread worldwide. The virus is primarily transmitted through respiratory droplets from infected persons; however, the virus-laden excretions can contaminate surfaces which can serve as a potential source of infection. Since the beginning of the pandemic, SARS-CoV-2 has continued to evolve and accumulate mutations throughout its genome leading to the emergence of variants of concern (VOCs) which exhibit increased fitness, transmissibility, and/or virulence. However, the stability of SARS-CoV-2 VOCs in biological fluids has not been thoroughly investigated so far. The aim of this study was to determine and compare the stability of different SARS-CoV-2 strains in human biological fluids. Here, we demonstrate that the ancestral strain of Wuhan-like lineage A was more stable than the Alpha VOC B.1.1.7, and the Beta VOC B.1.351 strains in human liquid nasal mucus and sputum. In contrast, there was no difference in stability among the three strains in dried biological fluids. Furthermore, we also show that the Omicron VOC B.1.1.529 strain was less stable than the ancestral Wuhan-like strain in liquid nasal mucus. These studies provide insight into the effect of the molecular evolution of SARS-CoV-2 on environmental virus stability, which is important information for the development of countermeasures against SARS-CoV-2.

Importance

Genetic evolution of SARS-CoV-2 leads to the continuous emergence of novel variants, posing a significant concern to global public health. Five of these variants have been classified so far into variants of concern (VOCs); Alpha, Beta, Gamma, Delta, and Omicron. Previous studies investigated the stability of SARS-CoV-2 under various conditions, but there is a gap of knowledge on the survival of SARS-CoV-2 VOCs in human biological fluids which are clinically relevant. Here, we present evidence that Alpha, Beta, and Omicron VOCs were less stable than the ancestral Wuhan-like strain in human biological fluids. Our findings highlight the potential risk of contaminated human biological fluids in SARS-CoV-2 transmission and contribute to the development of countermeasures against SARS-CoV-2.
Genetic analysis of a malaria outbreak in Laos driven by a selective sweep for Plasmodium falciparum kelch13 R539T mutants
Authors: Wasakul Varanya , Disratthakit Areeya , Mayxay Mayfong , Chindavongsa Keobouphaphone , Sengsavath Viengphone , Thuy-Nhien Nguyen , Pearson Richard D , Phalivong Sonexay , Xayvanghang Saiamphone , Gonçalves Sonia , Day Nicholas P , Newton Paul N , Ashley Elizabeth A , Kwiatkowski Dominic P , Dondorp Arjen M , Miotto Olivo
Published: August 2022

Malaria outbreaks are an important public health concern in endemic regions approaching elimination. Genetic surveillance of malaria parasites can elucidate the population dynamics of an outbreak, and help identify its causes. We investigated the epidemiology of a Plasmodium falciparum outbreak in Attapeu Province, Laos, during the 2020-2021 season. An analysis of 249 samples, collected by routine genetic surveillance during the outbreak, revealed a massive loss of genetic diversity in the parasite population, primarily caused by the rapid expansion of a multidrug resistant strain, named LAA1. This strain carried the kelch13 R539T mutation and expanded clonally, replacing the previously dominant kelch13 C580Y mutants (KEL1/PLA1) resistant to dihydroartemisinin-piperaquine. Identity by descent (IBD) patterns showed that LAA1 was a recombinant that inherited 60% of its genome from a strain first sampled in Cambodia over a decade ago. A less common outbreak strain (LAA2) carried the kelch13 C580Y allele, but was distinct from KEL1/PLA1, its genome essentially identical to that of a Cambodian parasite from 2009. A third, low-frequency strain (LAA7) was a recombinant of KEL1/PLA1 with a R539T mutant, the latter providing the kelch13 variant. These results strongly suggest that the outbreak was driven by a selective sweep, possibly associated with drug-resistant phenotypes of the outbreak strains. The observation that new variants of established multidrug resistant populations can overwhelm previously dominant strains so rapidly has implications for elimination of malaria. Genetic surveillance provides the tools for characterizing outbreaks, and for monitoring the evolution and spread of the populations involved.
Predicting work disability among people with chronic conditions: a large prospective cohort study
Authors: Nyberg Solja T. , Airaksinen Jaakko , Pentti Jaana , Ervasti Jenni , Jokela Markus , Vahtera Jussi , Virtanen Marianna , Elovainio Marko , Batty G. David , Kivimäki Mika
Published: August 2022

Few risk prediction scores are available to identify people at increased risk of work disability, particularly for those with an existing morbidity. We examined the predictive performance of disability risk scores for employees with chronic disease. We used prospective data from 88,521 employed participants (mean age 43.1) in the Finnish Public Sector Study which included people with chronic disorders: musculoskeletal disorder, depression, migraine, respiratory disease, hypertension, cancer, coronary heart disease, diabetes and comorbid depression and cardiometabolic disease. 105 predictors were assessed at baseline and participants were linked to a national disability pension register. During a mean follow-up of 8.6 years, 6836 (7.7%) participants got a disability pension, the incidence varying between 9.9% among participants with migraine and 27.7% in those with comorbid depression and cardiometabolic disease. C-statistics for an 8-item risk score, comprising age, self-rated health, number of sickness absences, socioeconomic position, number of chronic illnesses, sleep problems, BMI, and smoking at baseline, was 0.80 (95%CI: 0.80-0.81) for musculoskeletal disorders (N=33,601), 0.83 (0.82-0.84) for migraine (N=22,065), 0.82 (0.81-0.83) for respiratory disease (N=15,372) and exceeded 0.72 for other disease groups. With 30% estimated risk as a threshold, a positive test detection rate and false positive rate ranged from 42.2% and 18.8% (cancer) to 79.8% and 45.2% (comorbid depression and cardiometabolic disease). Predictive performance was not improved in models with a new set of predictors or re-estimated coefficients. In conclusion, the 8-item work disability risk score may serve as a scalable screening tool in identifying individuals with increased risk for work disability.
Detection of Monkeypox virus DNA in the wastewater of an airport in Rome, Italy: expanding environmental surveillance to emerging threats
Authors: La Rosa G , Mancini P , Veneri C , Bonanno Ferraro G , Lucentini L , Iaconelli M , Suffredini E.
Published: August 2022

Since May 2022, monkeypox cases have been reported in non-endemic countries, and the disease was declared a Public Health Emergency of International Concern. Rapid identification of new cases is critical for outbreak control. Environmental surveillance can be used as a complementary tool for detecting pathogens circulating in communities. This study aimed to investigate whether Monkeypox DNA can be detected in wastewater from a transportation hub.

Twenty samples were collected in Italy’s first airport in Rome and tested using published and modified real-time PCR assays targeting the G2R region (TFN gene), F3L, and N3R genes. Nested PCR assays were also used for confirmation by sequencing. Three samples tested positive by real-time PCR and/or by nested PCR, confirming the occurrence of the virus in the airport’s wastewater.

Wastewater surveillance can be quickly adapted to investigate emerging threats and can be used to track the introduction and/or the diffusion of the Monkeypox virus in communities.
Associations of the Triglyceride and Glucose Index with Hypertension Stages, Phenotypes, and Progressions among Middle-aged and Older Chinese
Authors: Shan Shiyi , Li Shuting , Lu Keyao , Cao Jin , Sun Weidi , Zhou Jiali , Ren Ziyang , Zhu Siyu , Hou Leying , Chen Dingwan , Song Peige
Published: August 2022

Background

The triglyceride and glucose (TyG) index has been proposed as a surrogate indicator of insulin resistance. By far, the associations of the TyG index with hypertension stages, phenotypes, and progressions remain unclear.

Methods

The data originated from two waves (2011 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS). Participants with systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or using antihypertensive medications were considered hypertensive. After excluding those under antihypertensive medications, hypertension stages were classified as stage 1 and stage 2, and phenotypes were classified as isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH). Multinomial logistic regression was used to investigate the associations of the TyG index with hypertension stages and phenotypes, together with their progressions from 2011 to 2015.

Results

At baseline in CHARLS 2011, a total of 8,209 participants were recruited, among whom 3,169 (38.6%) were hypertension. Compared with individuals with the lowest quartile (Q1) of TyG index, those with the highest quartile (Q4) were significantly associated with increased risks of stage 1 hypertension (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.38-2.13), stage 2 hypertension (1.74, 1.27-2.38), ISH (1.66, 1.31-2.11), IDH (2.52, 1.26-5.05), and SDH (1.65, 1.23-2.23). Similar results were found when the TyG index was used as a continuous variable. From 2011 to 2015, a higher baseline TyG index was revealed to be significantly associated with the progressions from normotension to stage 1 (for Q4 vs Q1: 1.45, 1.05-2.00; for per-unit: 1.39, 1.16-1.65), normotension to ISH (for per-unit: 1.28, 1.04-1.56), and normotension to IDH (for Q4 vs Q1: 3.46, 1.42-8.44; for per-unit: 1.94, 1.27-2.97).

Conclusions

The TyG index was significantly associated with different hypertension stages, phenotypes and their progressions. Our findings highlight the importance of the TyG index as a potential surrogate indicator for early hypertension screening and management.
Aiding Oral Squamous Cell Carcinoma diagnosis using Deep learning ConvMixer network
Authors: Toan Nguyen Quoc
Published: August 2022

In recent years, Oral squamous cell carcinoma (OSCC) has become one of the world’s most prevalent cancers, and it is becoming more prevalent in many populations. The high incidence rate, late diagnosis, and inadequate treatment planning continue to be major concerns. Despite the enhancement in the applications of deep learning algorithms for the medical field, late diagnosis, and approaches toward precision medicine for OSCC patients remain a challenge. Due to a lack of datasets and trained models with low computational costs, the diagnosis, an important cornerstone, is still done manually by oncologists. Although Convolutional neural networks (CNNs) have become the dominant architecture for vision tasks for plenty of years, recent experiments show that Transformer-based models, most noticeably the Vision Transformer (ViT), may out-compete them in some settings. Therefore, in this research, a method called ConvMixer, which combines great features from CNNs and patches based on ViT was applied to an original very small dataset of only 1224 images in total for 2 classes, Normal epithelium of the oral cavity (Normal) and OSCC, 696 slides for 400x magnification and 528 slides for 100x magnification. However, the proposed models with small parameters and data augmentation performed magnificently, with 400x magnification (Accuracy: 99.81% - F1score: 99.87%) and 100x magnification (Accuracy: 99.62% - F1score: 99.77%).
Quantifying decision-making in dynamic, continuously evolving environments
Authors: Ruesseler Maria , Weber Lilian AE , Marshall Tom R , O’Reilly Jill X , Hunt Laurence T
Published: August 2022

During perceptual decision-making tasks, centroparietal EEG potentials report an evidence accumulation-to-bound process that is time locked to trial onset. However, decisions in real-world environments are rarely confined to discrete trials; they instead unfold continuously, with accumulation of time-varying evidence being recency-weighted towards its immediate past. The neural mechanisms supporting recency-weighted continuous decision making remain unclear. Here, we use a novel continuous task design to study how the Centroparietal Positivity (CPP) adapts to different environments that place different constraints on evidence accumulation. We show that adaptations in evidence weighting to these different environments are reflected in changes in the CPP. The CPP becomes more sensitive to fluctuations in sensory evidence when large shifts in evidence are less frequent, and the potential is primarily sensitive to fluctuations in decision-relevant (not decision-irrelevant) sensory input. A complementary triphasic component over occipito-parietal cortex encodes the sum of recently accumulated sensory evidence, and its magnitude covaries with parameters describing how different individuals integrate sensory evidence over time. A computational model based on leaky evidence accumulation suggests these findings can be accounted for by a shift in decision threshold between different environments, which is also reflected in the magnitude of pre-decision EEG activity. Our findings reveal how adaptations in EEG responses reflect flexibility in evidence accumulation to the statistics of dynamic sensory environments.
DNA capture and loop extrusion dynamics by cohesin-NIPBL
Authors: Kaur Parminder , Shi Zhubing , Lu Xiaotong , Zhang Hongshan , Finkelstein Ilya J. , Tao Yizhi Jane , Yu Hongtao , Wang Hong
Published: August 2022

3D chromatin organization plays a critical role in regulating gene expression, DNA replication, recombination, and repair. While initially discovered for its role in sister chromatid cohesion, emerging evidence suggests that the cohesin complex (SMC1, SMC3, RAD21, and SA1/SA2), facilitated by NIPBL, mediates topologically associating domains (TADs) and chromatin loops through DNA loop extrusion. However, information on how conformational changes of cohesin-NIPBL drive its loading onto DNA, initiation, and growth of DNA loops is still lacking. Using high-speed AFM (HS-AFM) imaging, we show that cohesin-NIPBL captures DNA through arm extension, followed by transfer of DNA to its globular domain and DNA loop initiation independent of ATPase hydrolysis. Additional shorter protrusions (feet) from cohesin-NIPBL transiently bind to DNA, facilitating its loading onto DNA. Furthermore, HS-AFM imaging reveals distinct forward and reverse DNA loop extrusion steps by cohesin-NIPBL. These results provide critical missing links in our understanding of DNA binding and loop extrusion by cohesin-NIPBL.
A spatial map of human macrophage niches links tissue location with function
Authors: Matusiak Magdalena , Hickey John W. , Luca Bogdan , Lu Guolan , Kidzinski Lukasz , Shu Shirley , Colburg Deana Rae Crystal , Phillips Darci J. , Brubaker Sky W. , Charville Gregory W. , Shen Jeanne , Nolan Garry P. , Newman Aaron M. , West Robert B. , van de Rijn Matt
Published: August 2022

Macrophages are the most abundant immune cell type in the tumor microenvironment (TME). Yet the spatial distribution and cell interactions that shape macrophage function are incompletely understood. Here we use single-cell RNA sequencing data and multiplex imaging to discriminate and spatially resolve macrophage niches within benign and malignant breast and colon tissue. We discover four distinct tissue-resident macrophage (TRM) layers within benign bowel, two TRM niches within benign breast, and three tumor-associated macrophage (TAM) populations within breast and colon cancer. We demonstrate that IL4I1 marks phagocytosing macrophages, SPP1 TAMs are enriched in hypoxic and necrotic tumor regions, and a novel subset of FOLR2 TRMs localizes within the plasma cell niche. Furthermore, NLRP3 TAMs that colocalize with neutrophils activate an inflammasome in the TME and in Crohn’s disease and are associated with poor outcomes in breast cancer patients. This work suggests novel macrophage therapy targets and provides a framework to study human macrophage function in clinical samples.
NANOGP1, a tandem duplicate of NANOG, exhibits partial functional conservation in human naïve pluripotent stem cells
Authors: Maskalenka Katsiaryna , Alagöz Gökberk , Krueger Felix , Wright Joshua , Rostovskaya Maria , Nakhuda Asif , Bendall Adam , Krueger Christel , Walker Simon , Scally Aylwyn , Rugg-Gunn Peter J.
Published: August 2022

Gene duplication events are important drivers of evolution by providing genetic material for new gene functions. They also create opportunities for diverse developmental strategies to emerge between species. To study the contribution of duplicated genes to human early development, we examined the evolution and function of NANOGP1, a tandem duplicate of the key transcription factor NANOG. We found that NANOGP1 and NANOG have overlapping but distinct expression profiles, with high NANOGP1 expression restricted to early epiblast cells and naïve-state pluripotent stem cells. Sequence analysis and epitope-tagging of the endogenous locus revealed that NANOGP1 is protein-coding with an intact homeobox domain. NANOGP1 has been retained only in great apes, whereas Old World monkeys have disabled the gene in different ways including point mutations in the homeodomain. NANOGP1 is a strong inducer of naïve pluripotency; however, unlike NANOG, it is not required to maintain the undifferentiated status of human naïve pluripotent cells. By retaining expression, sequence and partial functional conservation with its ancestral copy, NANOGP1 exemplifies how gene duplication and subfunctionalisation can contribute to transcription factor activity in human pluripotency and development.

Summary statement

Establishing that NANOGP1 has retained partial functional conservation with its ancestral copy NANOG sheds light on the role of gene duplication and subfunctionalisation in human pluripotency and development.
Beat encoding at mistuned octaves within single sensory neurons
Authors: Barayeu Alexandra , Schäfer Ramona , Grewe Jan , Benda Jan
Published: August 2022

Beats are periodic amplitude modulations resulting from the superposition of two spectrally close periodic signals, where the difference between the two signal frequencies defines the frequency of the beat. Such amplitude modulations are known to be well encoded in corresponding firing rate modulations in auditory fibers as well as in electrosensory afferents. In a field study we showed the behavioral relevance of beat-like amplitude modulations exceeding spectrally close interactions in electric fish. Thus, we here study the encoding of beat-like waveforms over a wide range of difference frequencies in the electrosensory system ofApteronotus leptorhynchus. Contrary to expectations from the previously measured beat tuning, the activity of p-type electroreceptor afferents follows a repetitive pattern with slow modulations of their firing rate reoccurring around multiples of the frequency of the carrier signal. Mathematical reasoning supported by simulations of modified integrate-and-fire models reveals that neither Hilbert transform, squaring, harmonics of the carrier, half-wave rectification, nor the threshold-non-linearity of a spike generator are sufficient to extract slow beating signal envelopes around the octave of the carrier. Rather, a threshold operation smoothed out by exponentiation with a power of three is needed prior to spike generation to explain the repetitive occurrence of slow signal envelopes and electroreceptor responses. Our insights suggest the synapses of inner hair cells as candidate mechanisms underlying the perception of beats at mistuned octaves that has been described by Georg Simon Ohm, Hermann Helmholtz, and others already in the 19th century.
The impact of α-synuclein aggregates on blood-brain barrier integrity in the presence of neurovascular unit cells
Authors: Hourfar Hamdam , Aliakbari Farhang , Aqdam Shabboo Rahimi , Nayeri Zahra , Bardania Hassan , Otzen Daniel E. , Morshedi Dina
Published: August 2022

The role of the blood-brain barrier (BBB) is to control trafficking of biomolecules and protect the brain. This function can be compromised by pathological conditions. Parkinson’s disease (PD) is characterized by the accumulation of α-synuclein aggregates (αSN-AGs) such as oligomers and fibrils, which contribute to disease progression and severity. Here we study how αSN-AGs affect the BBB in in vitro co-culturing models consisting of human brain endothelial hCMEC/D3 cells alone and co-cultured with astrocytes and neurons/glial cells. When cultivated on their own, hCMEC/D3 cells were compromised by αSN-AGs, which decreased cellular viability, mitochondrial membrane potential, wound healing activity, TEER and permeability parameters, as well as increased the levels of ROS and NO. Co-culturing of these cells with activated microglia also increased BBB impairment according to TEER and systemic immune cell transmigration assays. In contrast, hCMEC/D3 cells co-cultured with astrocytes or dopaminergic neurons or simultaneously treated with their conditioned media showed increased resistance against αSN-AGs. Our work demonstrates the complex relationship between members of the neurovascular unit (NVU) (perivascular astrocytes, neurons, microglia, and endothelial cells), αSN-AGs and BBB.

Graphical Abstract
Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM
Authors: Saotome Kei , Dudgeon Drew , Colotti Kiersten , Moore Michael J. , Jones Jennifer , Zhou Yi , Rafique Ashique , Yancopoulos George D. , Murphy Andrew J. , Lin John C. , Olson William C. , Franklin Matthew C.
Published: August 2022

The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions.
Locating cellular contents during cryoFIB milling by cellular secondary-electron imaging
Authors: Lin Chao , Zhang Li , Zhang Ziying , Jiang Yifeng , Li Xueming
Published: August 2022

Cryo-electron tomography (cryoET) is a powerful technique that enables the direct study of the molecular structure of tissues and cells. Cryo-focused ion beam (cryoFIB) milling plays an important role in preparation of high-quality thin lamellar samples for cryoET studies, promoting the rapid development of cryoET in recent years. However, locating the regions of interest in a large cell or tissue during cryoFIB milling remains a major challenge limiting cryoET applications on arbitrary biological samples. Here, we report an on-the-fly location method based on cellular secondary electron imaging (CSEI). CSEI is derived from a basic imaging function of the cryoFIB instruments and enables high-contrast imaging of the cellular contents of frozen hydrated biological samples, highlighted by that both fluorescent labels and additional devices are not required. The present work discusses the imaging principles and settings for optimizing CSEI. Tests on several commercially available cryoFIB instruments demonstrated that CSEI was feasible on mainstream instruments to observe all types of cellular contents and was reliable under different milling conditions. Assisted by CSEI, we established a simple milling-location workflow and tested it using the basal body ofChlamydomonas reinhardtii.
Cryo-EM reveals the structure and dynamics of a 723-residue malate synthase G
Authors: Ho Meng-Ru , Wu Yi-Ming , Lu Yen-Chen , Ko Tzu-Ping , Wu Kuen-Phon
Published: August 2022

Determination of sub-100 kilodalton (kDa) structures by cryo-electron microscopy (EM) is a longstanding but not straightforward goal. Here, we present a 2.9-Å cryo-EM structure of a 723-amino acid apo-form malate synthase G (MSG) from Escherichia coli. The cryo-EM structure of the 82-kDa MSG exhibits the same global folding as structures resolved by crystallography and nuclear magnetic resonance (NMR) spectroscopy, and the crystal and cryo-EM structures are indistinguishable. Analyses of MSG dynamics reveal consistent conformational flexibilities among the three structural approaches, most notably that the α/β domain exhibits heterogeneity. We observed that sidechains of F453, L454, M629, and E630 residues involved in hosting the cofactor acetyl-CoA and substrate rotate differently between the cryo-EM apo-form and complex crystal structures. Our work demonstrates that the cryo-EM technique can be used to determine structures and conformational heterogeneity of sub-100 kDa biomolecules to a quality as high as that obtained from crystallography and NMR spectroscopy.