bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Death or Disability after Surgery in the Older Adult
Authors: Shulman Mark A. , Wallace Sophie , Gilbert Annie , Reilly Jennifer R. , Kasza Jessica , Myles Paul S.
Published: July 2023

Background

Older patients are vulnerable to developing new or worsening disability after surgery. Despite this, patient or surgical characteristics predisposing to postoperative disability are poorly defined. The aim of the study was to develop and validate a model, subsequently transformed to point-score form, to predict 6-month death or disability in older patients after surgery.

Methods

The authors built a prospective, single-center registry to develop and validate the prediction model. The registry included patients 70 yr of age or older undergoing elective and nonelective, cardiac and noncardiac surgery between May 25, 2017, and February 11, 2021, and combined clinical data from the electronic medical record, hospital administrative data (International Classification of Diseases, Tenth Revision, Australian Modification codes) and World Health Organization (Geneva, Switzerland) Disability Assessment Schedule data collected directly from the patients. Death or disability was defined as being dead or having a World Health Organization Disability Assessment Schedule score 16% or greater. Included patients were randomly divided into model development (70%) and internal validation (30%) cohorts. Once constructed, the logistic regression and point-score models were assessed using the internal validation cohort and an external validation cohort comprising data from a separate randomized trial.

Results

Of 2,176 patients who completed the World Health Organization Disability Assessment Schedule immediately before surgery, 927 (43%) patients were disabled, and 413 (19%) had significant disability. By 6 months after surgery, 1,640 patients (75%) had data available for the primary outcome analysis. Of these patients, 195 (12%) patients had died, and 691 (42%) were dead or disabled. The developed point-score model included the preoperative World Health Organization Disability Assessment Schedule score, patient age, dementia, and chronic kidney disease. The point score model retained good discrimination in the internal (area under the curve, 0.74; 95% CI, 0.69 to 0.79) and external (area under the curve, 0.77; 95% CI, 0.74 to 0.80) validation data sets.

Conclusions

The authors developed and validated a point score model to predict death or disability in older patients after surgery.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Maternal hypertensive traits and adverse outcome in pregnancy: a Mendelian randomization study
Authors: Ardissino Maddalena , Reddy Rohin K. , Slob Eric A.W. , Griffiths Jack , Girling Joanna , Ng Fu Siong
Published: July 2023

Introduction:

Hypertensive disorders of pregnancy are associated with adverse feto-maternal outcomes. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of component hypertensive indices on multiple adverse pregnancy outcomes using Mendelian randomization.

Methods:

Uncorrelated (r
2 < 0.001) genome-wide significant (P < 5 × 10−8) single-nucleotide polymorphisms associated with SBP, DBP and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of preeclampsia or eclampsia, preterm birth, placental abruption and hemorrhage in early pregnancy were extracted from summary statistics of genome-wide association studies in the FinnGen cohort. Two-sample, inverse-variance weighted Mendelian randomization formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically predicted hypertensive index.

Results:

Higher genetically predicted SBP were associated with higher odds of preeclampsia or eclampsia [OR 1.81, 95% confidence interval (CI) 1.68–1.96, P = 5.45 × 10−49], preterm birth (OR 1.09, 95% CI 1.03–1.16, P = 0.005) and placental abruption (OR 1.33, 95% CI 1.05–1.68, P = 0.016). Higher genetically-predicted DBP was associated with preeclampsia or eclampsia (OR 2.54, 95% CI 2.21–2.92, P = 5.35 × 10−40). Higher genetically predicted PP was associated with preeclampsia or eclampsia (OR 1.68, 95% CI 1.47–1.92, P = 1.9 × 10−14) and preterm birth (OR 1.18, 95% CI 1.06–1.30, P = 0.002).

Conclusion:

This study provides genetic evidence to support causal associations of SBP, DBP and PP on multiple adverse outcomes of pregnancy. SBP and PP were associated with the broadest range of adverse outcomes, suggesting that optimized management of blood pressure, particularly SBP, is a key priority to improve feto-maternal health.
Antihypertensive treatment in people of very old age with frailty: time for a paradigm shift?
Authors: Shantsila Eduard , Lip Gregory Y.H. , Shantsila Alena , Kurpas Donata , Beevers Gareth , Gill Paramjit S. , Williams Nefyn H.
Published: July 2023

The optimal management of hypertension in individuals aged 80 years or older with frailty remains uncertain due to multiple gaps in evidence. Complex health issues, polypharmacy, and limited physiological reserve make responding to antihypertensive treatments unpredictable. Patients in this age group may have limited life expectancy, so their quality of life should be prioritized when making treatment decisions. Further research is needed to identify which patients would benefit from more relaxed blood pressure targets and which antihypertensive medications are preferable or should be avoided. A paradigm shift is required in attitudes towards treatment, placing equal emphasis on deprescribing and prescribing when optimizing care. This review discusses the current evidence on managing hypertension in individuals aged 80 years or older with frailty, but further research is essential to address the gaps in knowledge and improve the care of this population.
Dietary factors and hypertension risk in West Africa: a systematic review and meta-analysis of observational studies
Authors: Batubo Nimisoere P. , Moore J. Bernadette , Zulyniak Michael A.
Published: July 2023

Background:

Contrary to North America and Europe, the prevalence of hypertension is rising in West Africa. Although diet is implicated as a contributor to this trend, nutritional guidelines in West Africa are not tailored to address this concern. This study aimed to address this limitation by investigating dietary factors common to West Africa and evaluating their association with hypertension.

Methods:

PubMed, Scopus, Web of Science, and Medline were searched to identify studies that investigated diet and hypertension in West African adults. All meta-analyses used a generic inverse-variance random effects model, with subgroup analyses by age, BMI, and study location, and were performed in R.

Results:

Three thousand, two hundred ninety-eight studies were identified, of which 31 (n = 48 809 participants) satisfied inclusion criteria – all cross-sectional. Meta-analyses of the association between dietary factors and hypertension included dietary fat [odds ratio (OR) = 1.76; 95% confidence interval (95% CI) 1.44–2.14; P < 0.0001], red meat (OR = 1.51; 95% CI: 1.04–2.18; P = 0.03), junk-food (OR = 1.41; 95% CI: 1.19–1.67; P < 0.0001), dietary salt (OR = 1.25; 95% CI: 1.12–1.40; P < 0.0001), alcohol (OR = 1.17; 95% CI: 1.03–1.32; P = 0.013), and ‘fruits and vegetables’ (OR = 0.80; 95% CI: 0.24–1.17; P < 0.0001). Subgroup analyses suggested that ‘fruit and vegetable’ consumption is less protective in the elderly.

Conclusion:

High consumption of dietary salt, red meat, dietary fat, junk food, and alcohol are associated with increased odds of hypertension, whereas high fruit and vegetable appear protective. This region-specific evidence will support the development of nutritional assessment tools for clinicians, patients, and researchers aiming to reduce hypertension in West Africa.
Research progress on central autonomic nervous mechanism of acupuncture at Neiguan point in the treatment of atrial fibrillation
Authors: Huang Jing , Yan Jinglan , Wang Taiyi , Chen Yongjun
Published: July 2023

Atrial fibrillation (AF) is the most common arrhythmia disease and is associated with several cardiovascular and cerebrovascular diseases. Consequently，the mortality rate of AF has increased in recent years. At present, the treatment of AF is mainly based on medication and radiofrequency ablation, but there are limitations such as adverse reactions and high recurrence rates. Recently, autonomic nervous regulation has become a new treatment for AF. Our previous study showed that acupuncture at Neiguan (PC6) point can treat AF by regulating autonomic balance. The autonomic nervous system can be structurally divided into the central autonomic nervous (CAN) and the peripheral autonomic nervous（PAN）. Several studies have shown a correlation between acupuncture and the treatment of AF and CAN. In the clinic the positive effect of acupuncture on AF has been realized gradually, and growing experimental studies have further discovered the potential mechanism of acupuncture on AF by regulating the CAN. Therefore, this review mainly focuses on summarizing the CAN mechanism related to acupuncture in the treatment of AF to provide new ideas and directions for the treatment of AF.
Factors Associated With Concussion Rates in Youth Ice Hockey Players: Data From the Largest Longitudinal Cohort Study in Canadian Youth Ice Hockey
Authors: Eliason Paul , Galarneau Jean-Michel , Shill Isla , Kolstad Ash , Babul Shelina , Mrazik Martin , Lebrun Constance , Dukelow Sean , Schneider Kathryn , Hagel Brent , Emery Carolyn
Published: July 2023

Objectives:

To examine factors associated with rates of game and practice-related concussion in youth ice hockey.

Design:

Five-year prospective cohort (Safe2Play).

Setting:

Community arenas (2013-2018).

Participants:

Four thousand eighteen male and 405 female ice hockey players (6584 player-seasons) participating in Under-13 (ages 11-12), Under-15 (ages 13-14), and Under-18 (ages 15-17) age groups.

Assessment of Risk Factors:

Bodychecking policy, age group, year of play, level of play, previous injury in the previous year, lifetime concussion history, sex, player weight, and playing position.

Main Outcome Measurements:

All game-related concussions were identified using validated injury surveillance methodology. Players with a suspected concussion were referred to a study sport medicine physician for diagnosis and management. Multilevel Poisson regression analysis including multiple imputation of missing covariates estimated incidence rate ratios (IRRs).

Main Results:

A total of 554 game and 63 practice-related concussions were sustained over the 5 years. Female players (IRRFemale/Male = 1.79; 95% CI: 1.26-2.53), playing in lower levels of play (IRR = 1.40; 95% CI: 1.10-1.77), and those with a previous injury (IRR = 1.46; 95% CI: 1.13, 1.88) or lifetime concussion history (IRR = 1.64; 95% CI: 1.34-2.00) had higher rates of game-related concussion. Policy disallowing bodychecking in games (IRR = 0.54; 95% CI: 0.40-0.72) and being a goaltender (IRRGoaltenders/Forwards = 0.57; 95% CI: 0.38-0.87) were protective against game-related concussion. Female sex was also associated with a higher practice-related concussion rate (IRRFemale/Male = 2.63; 95% CI: 1.24-5.59).

Conclusions:

In the largest Canadian youth ice hockey longitudinal cohort to date, female players (despite policy disallowing bodychecking), players participating in lower levels of play, and those with an injury or concussion history had higher rates of concussion. Goalies and players in leagues that disallowed bodychecking had lower rates. Policy prohibiting bodychecking remains an effective concussion prevention strategy in youth ice hockey.
Diversity and disparity in the treatment and care of sarcoidosis
Authors: Obi Ogugua Ndili
Published: July 2023

Purpose of review

Clinical presentation and outcomes in patients with sarcoidosis vary by race, gender, ethnicity, and geolocation. African Americans and female individuals have the highest incidence of disease. They are also more likely to present with more severe and more advanced forms of disease and to die from sarcoidosis. African American females have the highest disease-associated mortality, yet the mortality rate varies by geolocation. The diverse presentation and outcomes in sarcoidosis have often been attributed to genetics and biology, yet this may not be entirely so.

Recent findings

Several studies have shown that African Americans and female individuals are more likely to earn less and be more socioeconomically disadvantaged in society. Patients with sarcoidosis earning in the lowest income strata present with the most severe disease and report more barriers to care. It is plausible that the racial, gender, and geospatial differences in sarcoidosis are more reflective of healthcare disparities than genetics or biology alone.

Preventable differences in the burden of disease and in the opportunities to achieve optimal health outcomes that are differentially experienced by groups of people disadvantaged by race, gender, ethnicity, or socioeconomic background should be identified and addressed.
Impact of the Practice Environment on Oncology and Hematology Nurses
Authors: O’Dea Amy , Caulfield Rebecca , Roche Michael
Published: July 2023

Background

Practice environments have a significant impact on nurses’ practice and their retention within the oncology and hematology specialty. Understanding how specific elements of the practice environment impact nurse outcomes is important for creating supportive and safe practice environments.

Objective

To evaluate the impact of the practice environment on oncology and hematology nurses.

Methods

A scoping review was conducted according to the PRISMA-ScR Statement Guidelines. Electronic databases (MEDLINE, CINAHL, PsychINFO, Google Scholar, and Scopus) were searched using key terms. Articles were assessed according to the eligibility criteria. Data extraction was conducted with results explained through descriptive analysis.

Results

One thousand seventy-eight publications were screened with 32 publications meeting the inclusion criteria. The 6 elements of the practice environment (workload, leadership, collegial relations, participation, foundations, and resources) were found to significantly impact nurses’ job satisfaction, psychological well-being, levels of burnout, and intention to leave. Negative practice environment elements were linked to increased levels of job dissatisfaction, higher levels of burnout, greater prevalence of psychological distress, and greater intention to leave both oncology and hematology nursing and the nursing profession.

Conclusions

The practice environment has a significant impact on nurses, their job satisfaction, well-being, and intention to stay. This review will inform future research and forthcoming practice change to provide oncology and hematology nurses with practice environments that are safe and lead to positive nurse outcomes.

Implications for Practice

This review provides a foundation upon which to develop and implement tailored interventions that best support oncology and hematology nurses to remain in practice and provide high-quality care.
Effects of Preoperative High-Intensity Interval Training Combined With Team Empowerment Education in Lung Cancer Patients With Surgery
Authors: Lu Han-Bing , Wang Ya-Qing , Liu Xin , Ma Rui-Chen , Yin Ying-Ying , Song Chun-Yu , Yang Ting-Ting , Xie Jiao
Published: July 2023

Background

Cancer itself and surgery put a heavy burden on lung cancer patients, physiologically and psychologically. Enhancing self-efficacy during high-intensity interval training is essential for achieving the full benefit of pulmonary rehabilitation in lung cancer patients.

Objective

This study aimed to explore the effects of high-intensity interval training combined with team empowerment education on patients with lung resection.

Methods

This is a quasi-experimental trial with a pretest-posttest design. Participants were assigned to one of the 3 groups according to the order of admission: (1) combined intervention group, (2) intervention group, or (3) routine care group. The outcome measures included dyspnea, exercise capacity, exercise self-efficacy, anxiety, depression, postoperative indwelling time of thoracic drainage tube, and total in-hospital stay.

Results

Per-protocol results showed that dyspnea, exercise capacity, exercise self-efficacy, anxiety, and depression of the patients in the combined intervention group were significantly improved. However, no significant difference was observed in postoperative indwelling time of thoracic drainage tube or total in-hospital stay among the 3 groups.

Conclusion

This hospital-based short-term high-intensity interval training combined with team empowerment education for lung cancer patients undergoing surgery was safe and feasible, indicating this program can be a promising strategy to manage perioperative symptoms.

Implications for Practice

This study provides evidence supporting preoperative high-intensity interval training as a promising method to make the best use of preoperative time, thus improving adverse symptoms in lung cancer patients undergoing surgery, and also provides a new strategy to raise exercise self-efficacy and promote patients’ rehabilitation.
Jellybean-Induced Intoxication
Authors: Az Adem
Published: July 2023

Synthetic cannabinoids are illegal substances designed to mimic the effects of natural cannabinoids, typically smoked, although liquid formulations have emerged recently. This report highlights a series of cases ranging from a 2-year-old child to an adult who presented with symptoms of intoxication after consuming jellybeans containing liquefied synthetic cannabinoids. A 2-year-old child exhibited mental status changes, somnolence, tachycardia, dilated pupils, and flushed skin, and the 8- and 11-year-old children presented with anxiety, abdominal pain, vomiting, and nausea. The adult patient was more complicated, as his symptoms were consistent with acute coronary syndrome, but his angiography showed normal coronary arteries. It is important for forensic medical professionals and emergency physicians to be aware of the possibility of unintentional atypical exposure to synthetic cannabinoids and to handle suspected cases with care as part of their medical approach. These substances can have a range of effects on the body, and their use can lead to serious health consequences and even mortality.
“It’s a Different Conversation”: Qualitative Analysis of Pediatric Home-based Hospice/Palliative Care Visits’ Perceived Value
Authors: Grossoehme Daniel H. , Sellers Jaime , Accordino Samuel , Smith Steven M. , Jenkins Rachel , Richner Gwendolyn , Moore-Forbes Yolanda , Friebert Sarah
Published: July 2023

Introduction:

Home-based hospice and/or palliative care (HBHPC) is an important and increasingly utilized aspect of care for children with serious conditions—those with high mortality risk, which either impacts their quality of life or carries a significant caregiver burden. Provider home visits are a core feature; however, the travel time and human resource allocation are significant challenges. Balancing the appropriateness of this allocation requires further characterization of the value of home visits to families and identification of the value domains of HBHPC for caregivers. For study purposes, we defined a “home visit” as an in-person visit by a physician or advanced practice provider to a child’s residence.

Methods:

The methods include a qualitative study using semistructured interviews and a grounded theory analytic framework enrolled caregivers of children aged 1 month to 26 years receiving HBHPC from either of 2 U.S. pediatric quaternary institutions between 2016 and 2021.

Results:

Twenty-two participants were interviewed; the mean (SD) interview duration was 52.9 (22.6) minutes. The final conceptual model has 6 major themes: communicating effectively, fostering emotional and physical safety, building and maintaining relationships, empowering the family, seeing the bigger picture, and sharing burdens.

Conclusions:

Caregiver-identified themes demonstrated improved communication, empowerment, and support from receiving HBHPC, which can facilitate enhanced family-centered, goal-concordant care.
No evidence of rapid reversibility of tenofovir alafenamide and/or integrase strand transfer inhibitor-associated weight gain
Authors: Verburgh Myrthe L. , Wit Ferdinand W.N.M. , Boyd Anders , Reiss Peter , Van der Valk Marc
Published: July 2023

Objective:

We aimed to determine the reversibility of ≥7% weight gain (WG) within 12 months following TAF- and/or INSTI-discontinuation in people with HIV (PWH) from the Dutch ATHENA cohort.

Design and methods:

PWH with ≥7% WG within 24 months after first switch to TAF and/or INSTI whilst being virally suppressed were selected, excluding those with comorbidities/co-medication known to be associated with WG. PWH who discontinued only TAF, only INSTI or TAF+INSTI, with available follow-up weight, were included. Mean weight change in the 24 months prior to and 12 months after discontinuation was modelled using mixed-effects linear regression. Factors associated with yearly weight change were assessed using linear regression.

Results:

In 115 PWH, discontinuing only TAF (n = 39), only INSTI (n = 53) or TAF+INSTI (n = 23), the adjusted mean modelled weight change in the 24 months prior to discontinuation was +4.50 kg [95%CI, 3.04–6.10], +4.80 kg [95%CI, 2.43–7.03] and +4.13 kg [95%CI, 1.50–7.13], respectively, and -1.89 kg [95%CI, -3.40 to -0.37], -1.93 kg [95%CI, -3.92 to +0.07] and -2.55 kg [95%CI, -5.80 to +0.02] in the 12 months post-discontinuation. A greater number of years since HIV diagnosis was associated with greater reversibility of WG. No associations were found between weight change post-discontinuation and changes in NRTI backbone or anchor agent at moment of discontinuation.

Conclusions:

There was no evidence of rapid reversibility of ≥7% TAF- and/or INSTI-associated WG after discontinuation of these agents. Studies of larger and more diverse populations of PWH are required to more fully understand the degree to which WG is reversible when discontinuing TAF and/or INSTI.
Noninfectious causes of fever in hematologic malignancies. Are antibiotics still indicated?
Authors: Shahid Zainab , Epstein David J
Published: July 2023

Purpose of review

Fever is a common manifestation of both infectious and noninfectious processes in recipients of hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. Understanding the diverse causes of fever in these settings allows for accurate diagnosis and optimal use of antibiotics.

Recent findings

Herein we review common noninfectious syndromes seen in HCT and CAR-T recipients and discuss best practices in the management of these complex clinical scenarios regarding diagnosis and antibiotic use. In recent years, adverse effects of antimicrobials have highlighted the importance of antimicrobial stewardship in HCT and CAR-T patients, and an antibiotic de-escalation strategy is a safe and important tool in mitigating these adverse events, even in patients with ongoing neutropenia who become afebrile without a known infection. Common adverse events associated with antibiotics include an increased risk of Clostridiodes difficile infection (CDI), a higher incidence of multidrug-resistant organisms (MDROs), and microbiome dysbiosis.

Clinicians should be aware of noninfectious causes of fever in these immunocompromised patients and utilize best antibiotic practices while managing these patients.
Psychological support for chronic conditions
Authors: Solomons Luke , Farrar Catherine , Carpenter Lindsay
Published: July 2023

Purpose of review

Haematological conditions are varied, and every condition presents unique psychosocial challenges to patients and their families. There is a growing body of evidence about high levels of psychological distress, negative impact on outcomes and evidence-based treatments, yet service provision is patchy and demand far exceeds supply.

Recent findings

This article focuses on the major subspecialty areas and associated neuropsychiatric comorbidities – haematological malignancies, issues related to stem cell transplants, haemoglobinopathies and haemophilia. The subsequent sections focus on common psychiatric comorbidities, considerations across the life span and models of care.

Anxiety disorders and depression have higher prevalence in people with haematological conditions. The stressors faced by the individual can vary based on their condition and their stage of life. Early diagnosis and integrated management of comorbid psychiatric illness can improve quality of life and clinical outcomes. A stepped care model is recommended to ensure that psychological distress is identified and managed appropriately, and evidence for a collaborative care model is provided.
ICTV Virus Taxonomy Profile: Lispiviridae 2023
Authors: Li Jun-Min , Wang Fei , Ye Gongyin , Paraskevopoulou Sofia
Published: July 2023

Members of the family Lispiviridae are viruses with negative-sense RNA genomes of 6.5–15.5 kb that have mainly been found in arthropods and nematodes. The genomes of lispivirids contain several open reading frames, typically encoding a nucleoprotein (N), a glycoprotein (G), and a large protein (L) including an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Lispiviridae, which is available at ictv.global/report/lispiviridae.
An analysis of studies pertaining to masks in Morbidity and Mortality Weekly Report: Characteristics and quality of all studies from 1978 to 2023
Authors: Høeg Tracy Beth , Haslam Alyson , Prasad Vinay
Published: July 2023

Importance

Because the MMWR has substantial influence on United States public health policy and is not externally peer-reviewed, it is critical to understand the scientific process within the journal. Mask policies during COVID is one topic that has been highly influenced by data published in the MMWR.

Objective

To describe and evaluate the nature and methodology of the reports and appropriateness of conclusions in MMWR pertaining to masks.

Design, Setting and Participants

Retrospective cross-sectional study of MMWR publications pertaining to masks from 1978 to 2023.

Main outcome measures

Study date, design, disease focus, setting, population and location. Whether the study was able to assess mask effectiveness, if results were statistically significant, if masks were concluded to be effective, if randomized evidence and/or conflicting data was mentioned or cited, if causal statements were made about effectiveness, and, if so, whether they were appropriate.

Results

77 studies, all published after 2019, met our inclusion criteria. 75/77 (97.4%) studies were from the United States alone. All geographic regions and age groups were represented. The most common study design was observational without a comparator group 22/77 (28.6%). The most common setting was the community (35/77;45.5%). 0/77 were randomized studies. 23/77 (29.9%) assessed mask effectiveness, with 11/77 (14.3%) being statistically significant, but 58/77 (75.3%) stated masks were effective. Of these, 41/58 (70.7%) used causal language. Only one mannequin study used causal language appropriately (1.3%). 72/77 (93.5%) pertained to SARS-CoV-2 alone. None cited randomized data. 1/77 (1.3%) cited conflicting evidence.

Conclusions and Relevance

MMWR publications pertaining to masks drew positive conclusions about mask effectiveness over 75% of the time despite only 30% testing masks and <15% having statistically significant results. No studies were randomized, yet over half drew causal conclusions. The level of evidence generated was low and the conclusions drawn were most often unsupported by the data. Our findings raise concern about the reliability of the journal for informing health policy.
In VitroModulator Responsiveness of 655CFTRVariants Found in People With CF
Authors: Bihler Hermann , Sivachenko Andrey , Millen Linda , Bhatt Priyanka , Patel Amita Thakerar , Chin Justin , Bailey Violaine , Musisi Isaac , LaPan André , Allaire Normand E. , Conte Joshua , Simon Noah R. , Magaret Amalia S. , Raraigh Karen S. , Cutting Garry R. , Skach William R. , Bridges Robert J. , Thomas Phil J. , Mense Martin
Published: July 2023

Background

In 2017, the US Food and Drug Administration initiated expansion of drug labels for the treatment of cystic fibrosis (CF) to include CF transmembrane conductance regulator (CFTR) gene variants based onin vitrofunctional studies. This study aims to identifyCFTRvariants that result in increased chloride (Cl-) transport function by the CFTR protein after treatment with the CFTR-modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). These data may benefit people with CF (pwCF) who are not currently eligible for modulator therapies.

Methods

Plasmid DNA encoding 655 CFTR variants and wild-type (WT)CFTRwere transfected into Fisher Rat Thyroid cells that do not natively express CFTR. After 24 hours of incubation with control or TEZ and ELX, and acute addition of IVA, CFTR function was assessed using the transepithelial current clamp conductance assay. Each variant’s baseline activity, responsiveness to IVA alone, and responsiveness to the TEZ/ELX/IVA combination were measured in three different laboratories. Western blots were conducted to evaluate CFTR protein maturation and complement the functional data.

Results and Conclusions

253 variants not currently approved for CFTR modulator therapy showed low baseline activity (<10% of normal CFTR Cl-transport activity). For 152 of these variants, treatment with ELX/TEZ/IVA improved the Cl-transport activity by ≥10% of normal CFTR function, which is suggestive of clinical benefit. ELX/TEZ/IVA increased CFTR function by ≥10 percentage points for an additional 140 unapproved variants with ≥10% but <50% of normal CFTR function at baseline. These findings significantly expand the number of rare CFTR variants for which ELX/TEZ/IVA treatment should result in clinical benefit.
Circulating metabolites ofBorneolum syntheticum(Bingpian) inhibit foam-cell formation in macrophages induced by oxidized low-density lipoprotein
Authors: He Rong-rong , Li Hui , Chu Zi-xuan , Wang Feng-qing , Du Fei-fei , Xu Fang , Wang Jia-qi , Olaleye Olajide E. , Wang Ting , Cheng Chen , Li Chuan
Published: July 2023

Coronary heart disease is caused by the accumulation of atherosclerotic plaques which narrow the arteries over time. The plaques are formed by cholesterol deposits in the arterial intima and lead to the symptom of angina pectoris.Borneolum syntheticum(Bingpian) has been extensively used as a component in Chinese herbal medicines for cardiovascular diseases. This investigation aimed to examine Bingpian metabolism and its effects on anti-atherosclerotic activities. Major circulating Bingpian compounds were detected in human subjects who received a Bingpian-containing medicine. In vitro and rat studies were also conducted to facilitate the understanding of disposition factors that govern the systemic exposure to Bingpian compounds. Although Bingpian constituents, borneol (1) and isoborneol (2), are efficiently absorbed in the intestine, extensive hepatic first-pass glucuronidation, which is mediated predominantly by UGT2B7, coupled with MRP3 and MRP4-mediated efflux of the glucuronides into the blood, and oxidation, which is mediated by CYP2A6, CYP2B6, and CYP3A, result in the formation of metabolites borneol-2-O-glucuronide (M1G), isoborneol-2-O-glucuronide (M2G), and camphor (3) as the major circulating Bingpian compounds instead of the unchanged1and2. Glucuronides are predominantly eliminated through renal excretion, which involves both glomerular filtration and OAT3- and OAT4-mediated tubular secretion. Furthermore,M1G,M2G, and3, as well as1and2, displayed inhibitory effects on oxidized low-density lipoprotein-induced foam-cell formation in macrophages. The findings emphasized that the metabolites must be given priority in pharmacodynamic studies of Bingpian. Comprehensive integration of pharmacokinetic and pharmacodynamic studies facilitates understanding how Bingpian functions in the body to provide therapeutic benefits.
Population structure can reduce clonal interference when sexual reproduction and dispersal are synchronized
Authors: Liu Qihan , Weissman Daniel B.
Published: July 2023

In populations with limited recombination, clonal interference among beneficial mutations limits the maximum rate of adaptation. Spatial structure slows the spread of beneficial alleles; in purely asexual populations, this increases the amount of clonal interference. Beyond this extreme case, however, it is unclear how spatial structure and recombination interact to determine the amount of clonal interference. This interaction is particularly interesting because dispersal and recombination are often at least partially synchronized in natural populations, both at the individual and population level, as when plants switch from vegetative growth to sexual reproduction or stress responses increase both motility and recombination in microbes. We simulate island models of populations evolving on a smooth fitness landscape and find that synchronized dispersal and sexual reproduction allow them to adaptfasterthan matched well-mixed populations. This is because the spatial structure preserves genetic diversity, while the synchronization increases the chance that recombination events occur between diverged individuals from different demes, i.e., the pairings where negative linkage disequilibrium can most effectively be reduced.
Detection and editing of the updated plastid- and mitochondrial-encoded proteomes forArabidopsiswith PeptideAtlas
Authors: van Wijk Klaas J. , Bentolila Stephane , Leppert Tami , Sun Qi , Sun Zhi , Mendoza Luis , Li Margaret , Deutsch Eric W.
Published: July 2023

Arabidopsis thalianaCol-0 has plastid and mitochondrial genomes encoding for over one hundred proteins and several ORFs. Public databases (e.g.Araport11) have redundancy and discrepancies in gene identifiers for these organelle-encoded proteins. RNA editing results in changes to specific amino acid residues or creation of start and stop codons for many of these proteins, but the impact of such RNA editing at the protein level is largely unexplored due to the complexities of detection. This study first assembled the non-redundant set of identifiers, their correct protein sequences, and 452 predicted non-synonymous editing sites of which 56 are edited at lower frequency. Accumulation of edited and/or unedited proteoforms was then determined by searching ∼259 million raw MSMS spectra from ProteomeXchange as part of Arabidopsis PeptideAtlas (www.peptideatlas.org/builds/arabidopsis/). All mitochondrial proteins and all except three plastid-encoded proteins (NDHG/NDH6, PSBM, RPS16), but none of the ORFs, were identified; we suggest that all ORFs and RPS16 are pseudogenes. Detection frequencies for each edit site and type of edit (e.g.S to L/F) were determined at the protein level, cross-referenced against the metadata (e.g.tissue), and evaluated for technical challenges of detection.167 predicted edit sites were detected at the proteome level. Minor frequency sites were indeed also edited at low frequency at the protein level. However, except for sites RPL5-22 and CCB382-124, proteins only accumulate in edited form (>98 –100% edited) even if RNA editing levels are well below 100%. This study establishes that RNA editing for major editing sites is required for stable protein accumulation.
Novel genetic model of pediatric Diffuse Intrinsic Pontine Glioma inDrosophila melanogaster
Authors: de Pablo Carmen , Casas-Tintó Sergio
Published: July 2023

Diffuse Intrinsic Pontine Glioma (DIPG) is a lethal pediatric type of brain tumor that grows in the bm and originated from glial cells. Its location and infiltrative nature impede surgical resection and make the treatment difficult and low effective. In consequence, affected children have a short life expectancy of 12 months. The most frequent mutation is a substitution of lysine to methionine at residue 27 of histone H3 (H3K27M). Secondary mutations in additional genes, includingMyc, are required for the malignancy of glial cells. The lack of studies and tumor aggressiveness make it necessary to generate new experimental models that reproduce the fundamental aspects of the disease and allow to expand the knowledge about DIPG.

Drosophila melanogasterpresents advantages as an experimental model and stands out for its genetic tools, easy handling, and great genetic and cellular homology with humans.Drosophilahas contributed to the investigation of different diseases, including glioblastoma (GB) and neurodegenerative diseases as Alzheimeŕs or Parkinsońs. Here we present a new genetic model of DIPG generated inDrosophila melanogaster. It is based on the overexpression ofH3K27andMycin glial cells that produce an increase in the number of glial cells in the ventral nerve cord and the expansion of glial membranes in early developmental stages. However, this novel DIPG model does not produce tumoral features in adult brains, in line with the pediatric nature of this disease. We have evaluated the activation of different signaling pathways active in other glial tumors, in this model of DIPG. The results show that, unlike GB, JNK pathway is not upregulated in DIPG, and it is not determinant for the progression of DIPG. Besides, glial cells in the DIPG model accumulate MMP1 and MMP2 and increase the accumulation of Liprin-γ, previously associated to the formation of synaptic structures in GB cells. The results show that DIPG is a unique entity that differs from other high-grade gliomas such as GB and will require of a different therapeutic approach.
Mesophyll-specific overexpressing ofSvHXK6gene improves water use efficiency without yield loss in C4Setaria viridis
Authors: Chaudhari Yogesh , Chen Lily , Salam Shahasad , Paul Matthew , Furbank Robert , Ghannoum Oula
Published: July 2023

Hexokinases (HXK) were the first sugar signalling proteins identified in plants and are well known for their feedback regulation of photosynthetic gene expression. In some C3plants, HXKs have been found to regulate stomatal function. However, the role of HXK in C4photosynthesis, which is inherently more water use efficient than C3metabolism, remains poorly understood. Here, we report on the first tissue-specific modification of HXK in a C4plant.SvHXK6was expressed in the model C4grassSetaria viridisunder the control of theZmPEPCpromoter (ZmPEPCpro), which directs expression in the leaf mesophyll tissue. ThreeS. viridistransgenic lines with increased abundance ofSvHXK6transcripts in the leaf tissue showed significant reduction in stomatal conductance with minimal effects on leaf CO2assimilation rate. Consequently, the transgenic lines had higher leaf-level water use efficiency relative to the control (wild-type and null) plants. Overexpression ofSvHXK6had no effect on shoot biomass or seed yield of theS. viridisplants. Our study shows conserved function of HXK in regulating stomatal conductance in a C4grass, demonstrating possible widespread utility in improving water use efficiency in C4as well as C3species.
Swimmer’s itch control: timely waterfowl brood relocation significantly reduces an avian schistosome population and human cases on recreational lakes
Authors: Blankespoor Curtis L. , Blankespoor Harvey D. , DeJong Randall J.
Published: July 2023

Swimmer’s itch (SI) is a dermatitis in humans caused by cercariae of avian and mammalian schistosomes which emerge from infected snails on a daily basis. Mitigation methods for SI have long been sought with little success. Copper sulfate application to the water to kill the snail hosts is the historically employed method, but is localized, temporary, and harmful to many aquatic species. Here, we test an alternative method to controlTrichobilharzia stagnicolae, a species well-known to cause SI in northern Michigan and elsewhere in North America. Summer relocation of broods of the only known vertebrate host, common merganser (Mergus merganser),greatly reduced snail infection prevalence the following year on two large, geographically separated lakes in northern Michigan. Subsequent years of host relocation achieved and maintained snail infection prevalence at ∼0.05%, more than an order of magnitude lower than pre-intervention. A Before – After – Control – Intervention (BACI) study design using multiple-year snail infection data from two intervention lakes and three control lakes demonstrates that substantial lake-wide reduction of an avian schistosome can be achieved and is not due to natural fluctuations in the parasite populations. The relevance of reducing snail infection prevalence is demonstrated by a large seven-year data set of SI incidence in swimmers at a high-use beach, which showed a remarkable reduction in SI cases in two successive years after relocation began. In addition, data from another Michigan lake where vertebrate-host based intervention occurred in the 1980’s is analyzed statistically and shows a remarkably similar pattern of reduction in snail infection prevalence. Together, these results demonstrate a highly effective SI mitigation strategy that avoids the use of environmentally suspect chemicals and removes incentive for lethal host removal. Biologically, the results strongly suggest thatT. stagnicolaeis reliant on the yearly hatch of ducklings to maintain populations at high levels on a lake and that the role of migratory hosts in the spring and fall is much less significant.
Translational regulation by uORFs and start codon selection stringency
Authors: Dever Thomas E. , Ivanov Ivaylo P. , Hinnebusch Alan G.
Published: July 2023

In addition to the main, protein-coding, open reading frame (mORF), many eukaryotic mRNAs contain upstream ORFs (uORFs) initiated at AUG or near-cognate codons residing 5′ of the mORF start site. Whereas translation of uORFs generally represses translation of the mORFs, a subset of uORFs serves as a nexus for regulating translation of the mORF. In this review, we summarize the mechanisms by which uORFs can repress or stimulate mRNA translation, highlight uORF-mediated translational repression involving ribosome queuing, and critically evaluate recently described alternatives to the delayed reinitiation model for uORF-mediated regulation of theGCN4/ATF4mRNAs.
Pattern separation of fear extinction memory
Authors: Laing Patrick A.F. , Dunsmoor Joseph E.
Published: July 2023

While fear generalizes widely, extinction is stimulus-specific. Using a hybrid conditioning/episodic memory paradigm, subjects encoded nonrepeating category exemplars during fear conditioning and extinction. Twenty-four hours later, a surprise memory test included old, similar, and novel category exemplars. Results showed strong dissociation between pattern completion (generalization) and pattern separation (discrimination) in episodic memory for items encoded during fear conditioning versus extinction, respectively. These data suggest that directly threat-conditioned stimuli are better recognized at the expense of mnemonic precision, whereas discrimination is enhanced for extinguished stimuli. Overly precise extinction memory may be a contributing factor to fear relapse.
Crystal structure of K6[Zn(CO3)4]
Authors: Eder Felix , Weil Matthias
Published: July 2023

The crystal structure of K6[Zn(CO3)4], hexapotassium tetracarbonatozincate(II), comprises four unique potassium cations (two located on a general position, and two on the twofold rotation axis of the space groupC2/c) and a [Zn(CO3)4]6−anion. The ZnIIatom of the latter is located on the twofold rotation axis and is surrounded in a slightly distorted tetrahedral manner by two pairs of monodentately binding carbonate groups, with Zn—O distances of 1.9554 (18) and 1.9839 (18) Å. Both carbonate groups exhibit a slight deviation from planarity, with the C atom being shifted by 0.008 (2) and 0.006 (3) Å, respectively, from the plane of the three O atoms. The coordination numbers of the potassium cations range from 6 to 8, using a threshold of 3.0 Å for K—O bonding interactions being significant. In the crystal structure, [KOx] polyhedra and [Zn(CO3)4]6−groups share O atoms to build up the framework structure.
4-Methyl-2-(2-methylanilino)benzoic acid
Authors: Liu Chenxin , Long Sihui
Published: July 2023

The title compound, C15H15NO2, was obtained by the reaction of 2-chloro-4-methyl-benzoic acid and o-toluidine using 2-ethoxyethanol as solvent. Crystals of the title compounds were obtained from crystallization in acetone. The molecule in the crystal is twisted with a dihedral angle between the aromatic rings of 50.86 (5)°. In the crystal structure, the molecules associate to form acid–acid hydrogen-bonded dimers linked by pairwise O—H...O hydrogen bonds.
Review of the application of digital holography in corrosion studies
Authors: Gu Yunzhou , Yuan Boyu , Li Liang
Published: July 2023

Purpose

The purpose of this paper is to review the application of digital holography in studies of the corrosion of metallic materials.

Design/methodology/approach

Digital holography is used for in situ observation of the dynamic processes at the electrode | electrolyte interface and on the electrode surface during the corrosion dissolution of metallic materials.

Findings

Digital holography is an effect method to in situ observe the corrosion processes, and it can provide a direct experimental foundation for studying the corrosion mechanism.

Originality/value

Even though there are several challenges, digital holography will play a significant role in studying corrosion processes.
Is texture the new taste? The effect of sensory food descriptors on restaurant menus on visit intentions
Authors: Garaus Marion , Weismayer Christian , Steiner Elisabeth
Published: July 2023

Purpose

This study investigates the impact of sensory food descriptors on restaurant menus on the intention to visit a restaurant and to spread positive word-of-mouth.

Design/methodology/approach

Drawing on the signalling theory and the assimilation-contrast theory, two online experiments and one field experiment test the assumption that food descriptors prompt food-quality inferences before and after consumption, and that in both stages, food-quality inferences prompt favourable behavioural intentions.

Findings

Sensory food descriptors impact positively on behavioural intentions through quality inferences, although not all aspects of food quality mediate this effect.

Research limitations/implications

Not all four factors (deliciousness, visual attractiveness, variety and nutritiousness) prompt behavioural intentions to the same extent. While the signalling theory explains the positive impact of food-quality inferences on behavioural intentions before consumption, the assimilation-contrast theory explains the positive effect food-quality inferences have on the intention to revisit and word of mouth after consumption.

Practical implications

Managers should use either oral somatosensory descriptors alone, or in combination with flavour descriptors to prompt quality inferences and behavioural intentions.

Originality/value

The findings challenge the prevailing assumption that food descriptors addressing multiple senses have a superior effect on food-quality inferences compared to food descriptors stimulating only one sense. Instead, food descriptors referring to the texture, viscosity or mouthfeel of a dish, (i.e. oral somatosensory descriptors), impact on food-quality inferences, while adding flavour attributes did not have favourable effects.