bluuebunny/crossref_metadata_2025 huggingface dataset:
The therapeutic threshold in clinical decision-making for TB
Authors: de Rooij Madeleine L , Lynen Lutgarde , Decroo Tom , Henriquez-Trujillo Aquiles R , Boyles Tom , Jacobs Bart K M
Published: February 2023

Because TB control is still hampered by the limitations of diagnostic tools, diagnostic uncertainty is common. The decision to offer treatment is based on clinical decision-making. The therapeutic threshold, test threshold and test-treatment threshold can guide in making these decisions. This review summarizes the literature on methods to estimate the therapeutic threshold that have been applied for TB. Only five studies estimated the threshold for the diagnosis of TB. The therapeutic threshold can be estimated by prescriptive methods, based on calculations, and by descriptive methods, deriving the threshold from observing clinical practice. Test and test-treatment thresholds can be calculated using the therapeutic threshold and the characteristics of an available diagnostic test. Estimates of the therapeutic threshold for pulmonary TB from intuitive descriptive approaches (20%–50%) are higher than theoretical prescriptive calculations (2%–3%). In conclusion, estimates of the therapeutic threshold for pulmonary TB depend on the method used. Other methods exist within the field of decision-making that have yet to be implemented or adapted as tools to estimate the TB therapeutic threshold. Because clinical decision-making is a core element of TB management, it is necessary to find a new, clinician-friendly way to unbiasedly estimate context-specific, agreed upon therapeutic thresholds.
Repeat-associated non-AUG translation in neuromuscular diseases: mechanisms and therapeutic insights
Authors: Fujino Yuzo , Mori Kohji , Nagai Yoshitaka
Published: February 2023

Expanded short tandem repeats cause more than 50 monogenic diseases, which are mostly neuromuscular diseases. In the non-coding repeat expansion diseases, in which the expanded repeat sequence is located outside of the coding region, the toxicity of the transcribed repeat-containing RNAs had been the focus of research. However, recent studies have revealed that repeat RNAs can be translated into repeat polypeptides, despite the lack of an AUG initiation codon, by non-canonical repeat-associated non-AUG translation (RAN translation). RAN translated repeat polypeptides have actually been confirmed in patients’ tissues. Moreover, various cellular and animal disease models have demonstrated the toxicity of these peptides, suggesting the pathogenic roles of RAN translation in the repeat expansion diseases. In this review, we will outline RAN translation, from the viewpoint of its molecular mechanisms to its potential as a therapeutic target for the repeat expansion diseases.
Acetophenone and Green Leaf Volatiles Do Not Enhance the Efficacy of Verbenone for Inhibiting Attraction of Ips pini (Coleoptera: Curculionidae) to Pheromone-baited Traps in Northern Arizona
Authors: Gaylord Monica L , Audley Jackson P , McMillin Joel D , Fettig Christopher J
Published: February 2023

We assessed attraction of pine engraver, Ips pini (Say) (Coleoptera: Curculionidae; Scolytinae), to pheromone-baited funnel traps treated with repellent semiochemicals in ponderosa pine, Pinus ponderosa var. scopulorum Engelm., forests in northern Arizona. Treatments included: 1) baited control (B, ipsdienol + lanierone), 2) 70 g of SPLAT Verb (a flowable, biodegradable formulation containing 10% verbenone, ISCA Technologies Inc., Riverside, CA, USA) + B, 3) 70 g of SPLAT Verb + (E)-2-hexen-1-ol+(Z)-2-hexen-1-ol + acetophenone + B, 4) 7.84-g verbenone pouch (Product #3413, Synergy Semiochemicals Corp., Delta, British Columbia, Canada) + B, and 5) 7.84-g verbenone pouch + (E)-2-hexen-1-ol+(Z)-2-hexen-1-ol + acetophenone + B. In total, 472 I. pini were collected. Trap catches were highest in baited traps and declined significantly with the addition of both formulations of verbenone. Traps treated with SPLAT Verb caught significantly fewer I. pini and male I. pini than those treated with verbenone pouches. The addition of (E)-2-hexen-1-ol+(Z)-2-hexen-1-ol + acetophenone to SPLAT Verb and the verbenone pouch had no effect on trap catch. Verbenone has potential as an effective tool for protecting P. ponderosa trees and slash from I. pini in northern Arizona, but the addition of (E)-2-hexen-1-ol+(Z)-2-hexen-1-ol + acetophenone to verbenone is unwarranted.
Common analgesics and ovarian cancer survival: the Ovarian cancer Prognosis And Lifestyle (OPAL) Study
Authors: Majidi Azam , Na Renhua , Jordan Susan J , DeFazio Anna , Obermair Andreas , Friedlander Michael , Grant Peter , Webb Penelope M
Published: February 2023

Background

Most women with ovarian cancer (OC) are diagnosed with advanced disease. They often experience recurrence after primary treatment, and their subsequent prognosis is poor. Our goal was to evaluate the association between use of nonsteroidal antiinflammatory drugs (NSAIDs), including regular and low-dose aspirin, and 5-year cancer-specific survival after an OC diagnosis.

Methods

The Ovarian cancer Prognosis And Lifestyle study is a prospective population-based cohort of 958 Australian women with OC. Information was gathered through self-completed questionnaires. We classified NSAID use during the year prediagnosis and postdiagnosis as none or occasional (<1 d/wk), infrequent (1-3 d/wk), and frequent (≥4 d/wk) use. We measured survival from the start of primary treatment: surgery or neoadjuvant chemotherapy for analyses of prediagnosis use, or 12 months after starting treatment (postdiagnosis use) until the earliest of date of death from OC (other deaths were censored) or last follow-up to 5 years. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and applied inverse-probability of treatment weighting to minimize confounding. We also calculated restricted mean survival times.

Results

Compared with nonusers and infrequent users, we observed better survival associated with frequent NSAID use prediagnosis (HR = 0.73, 95% CI = 0.55 to 0.97) or postdiagnosis (HR = 0.65, 95% CI = 0.45 to 0.94). Estimates were similar for aspirin and nonaspirin NSAIDs, new and continuous users and in weighted models. These differences would translate to a 2.5-month increase in mean survival by 5 years postdiagnosis. There was no association with acetaminophen.

Conclusions

Our findings confirm a previous study suggesting NSAID use might improve OC survival.
Ku–DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks
Authors: Mendoza-Munoz Pamela L , Gavande Navnath S , VanderVere-Carozza Pamela S , Pawelczak Katherine S , Dynlacht Joseph R , Garrett Joy E , Turchi John J
Published: February 2023

The DNA-dependent protein kinase (DNA-PK) plays a critical role in the DNA damage response (DDR) and non-homologous end joining (NHEJ) double-strand break (DSB) repair pathways. Consequently, DNA-PK is a validated therapeutic target for cancer treatment in certain DNA repair-deficient cancers and in combination with ionizing radiation (IR). We have previously reported the discovery and development of a novel class of DNA-PK inhibitors with a unique mechanism of action, blocking the Ku 70/80 heterodimer interaction with DNA. These Ku–DNA binding inhibitors (Ku-DBi's) display nanomolar activity in vitro, inhibit cellular DNA-PK, NHEJ-catalyzed DSB repair and sensitize non-small cell lung cancer (NSCLC) cells to DSB-inducing agents. In this study, we demonstrate that chemical inhibition of the Ku–DNA interaction potentiates the cellular effects of bleomycin and IR via p53 phosphorylation through the activation of the ATM pathway. This response is concomitant with a reduction of DNA-PK catalytic subunit (DNA-PKcs) autophosphorylation at S2056 and a time-dependent increase in H2AX phosphorylation at S139. These results are consistent with Ku-DBi's abrogating DNA-PKcs autophosphorylation to impact DSB repair and DDR signaling through a novel mechanism of action, and thus represent a promising anticancer therapeutic strategy in combination with DNA DSB-inducing agents.
Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment
Authors: Koeniger Anke , Polo Pierfrancesco , Brichkina Anna , Finkernagel Florian , Visekruna Alexander , Nist Andrea , Stiewe Thorsten , Daude Michael , Diederich Wibke E , Gress Thomas M , Adhikary Till , Lauth Matthias
Published: February 2023

Transcriptional cancer subtypes which correlate with traits such as tumor growth, drug sensitivity or the chances of relapse and metastasis, have been described for several malignancies. The core regulatory circuits (CRCs) defining these subtypes are established by chromatin super enhancers (SEs) driving key transcription factors (TFs) specific for the particular cell state. In neuroblastoma (NB), one of the most frequent solid pediatric cancer entities, two major SE-directed molecular subtypes have been described: A more lineage-committed adrenergic (ADRN) and a mesenchymal (MES) subtype. Here, we found that a small isoxazole molecule (ISX), a frequently used pro-neural drug, reprogrammed SE activity and switched NB cells from an ADRN subtype towards a growth-retarded MES-like state. The MES-like state shared strong transcriptional overlap with ganglioneuroma (GN), a benign and highly differentiated tumor of the neural crest. Mechanistically, ISX suppressed chromatin binding of N-MYC, a CRC-amplifying transcription factor, resulting in loss of key ADRN subtype-enriched components such as N-MYC itself, PHOX2B and ALK, while concomitently, MES subtype markers were induced. Globally, ISX treatment installed a chromatin accessibility landscape typically associated with low risk NB. In summary, we provide evidence that CRCs and cancer subtype reprogramming might be amenable to future therapeutic targeting.
Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities
Authors: Mahmoud Ahmed M , Nabavizadeh Reza , Rodrigues Pessoa Rodrigo , Garg Ishita , Orme Jacob , Costello Brian A , Cheville John , Lucien Fabrice
Published: February 2023

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies. Despite positive results for hematological cancers, breast cancer, and more recently bladder cancer, most antibody-based therapies failed to improve the outcomes in patients with advanced RCC. This underscores the need to understand the underlying causes of failed responses to this treatment class, which will ultimately support the rational design of more effective and tolerable treatments. In this review, we summarize the evolving landscape of RCC therapeutics and describe recent clinical trials with emerging antibody-based therapeutics. We also describe the challenges that need to be overcome for the successful creation of therapeutic antibodies for treating RCC.
SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis
Authors: Bi Yang , Shrestha Ruben , Zhang Zhenzhen , Hsu Chuan-Chih , Reyes Andres V , Karunadasa Sumudu , Baker Peter R , Maynard Jason C , Liu Yang , Hakimi Amirmansoor , Lopez-Ferrer Daniel , Hassan Tahmid , Chalkley Robert J , Xu Shou-Ling , Wang Zhi-Yong
Published: February 2023

The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. Genetic evidence indicates the important roles of SPY in diverse developmental and physiological processes. However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. The O-fucosylome includes mostly nuclear and cytosolic proteins. Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. The O-fucosylome also includes many proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development.
A novel biomimetic trabecular bone metal plate for bone repair and osseointegration
Authors: Ma Zhijie , Liu Baoyi , Li Shuqiang , Wang Xiaohu , Li Jingyu , Yang Jiahui , Tian Simiao , Wu Chengjun , Zhao Dewei
Published: February 2023

Fracture is one of the most common traumatic diseases in clinical practice, and metal plates have always been the first choice for fracture treatment because of their high strength. However, the bone plates have high elastic modulus and do not match the biomechanics of human bone, which adversely affects callus formation and fracture healing. Moreover, the complex microenvironment in the human body can induce corrosion of metallic materials and release toxic ions, which reduces the biocompatibility of the bone plate, and may necessitate surgical removal of the implant. In this study, tantalum (Ta) was deposited on porous silicon carbide (SiC) scaffolds by chemical vapor deposition technology to prepare a novel porous tantalum (pTa) trabecular bone metal plate. The function of the novel bone plate was evaluated by implantation in an animal fracture model. The results showed that the novel bone plate was effective in fracture fixation, without breakage. Both X-ray and microcomputed tomography analysis showed indirect healing by both pTa trabecular bone metal plates and titanium (Ti) plates; however, elastic fixation and obvious callus formation were observed after fixation with pTa trabecular bone metal plates, indicating better bone repair. Histology showed that pTa promoted the formation of new bone and integrated well with the host bone. Therefore, this novel pTa trabecular bone metal plate has good prospects for application in treating fractures.
Does Socially Responsible Investing Change Firm Behavior?
Authors: Heath Davidson , Macciocchi Daniele , Michaely Roni , C. Ringgenberg Matthew
Published: February 2023

Using micro-level data, we examine the behavior of socially responsible investment (SRI) funds. SRI funds select firms with lower pollution, more board diversity, higher employee satisfaction, and better workplace safety. Yet, both in the cross-section and using an exogenous shock to SRI capital, we find that SRI funds do not significantly change firm behavior. Moreover, we find little evidence that they try to impact firm behavior using shareholder proposals. Our results suggest that SRI funds are not greenwashing, but they are impact washing; they invest in a portfolio of firms with better environmental and social conduct but do not follow through on their promise of impact.
EPR DOSIMETRIC PROPERTIES OF DI-SODIUM TARTRATE
Authors: Maghraby Ahmed M , Ahmed Monem A , Eissa H M
Published: February 2023

A new dosimetry system based on di-sodium tartrate was investigated. Unirradiated and irradiated sample spectra were recorded and described. Effects of the change in microwave power and modulation amplitude values on the signal amplitude and the line width of the two peaks were plotted. Response to the Cs-137 gamma radiation was studied in two ranges: high-dose range (2409.66–41.97) Gy and low-dose range (41.97–1.40) Gy. The first peak of di-sodium tartrate is found to be 1.2 times more sensitive than that of alanine in the dose range (2409.66–41.97) Gy; moreover, in the dose range (41.97–1.40) Gy, it is found to be 1.3 times more than that of alanine. For the second peak of di-sodium tartrate, it is found to be less sensitive than that of alanine in the dose range (2409.66–41.97) Gy by a factor of 0.41, whereas in the dose range (41.97–1.40) Gy, it is found to be 0.44 times less than that of alanine The minimum detectable dose for di-sodium tartrate is about 0.05 Gy for the first peak and 1.4 Gy for the second peak.
How and Why the Circadian Clock Regulates Proliferation of Adult Epithelial Stem Cells
Authors: Andersen Bogi , Duan Junyan , Karri Satya Swaroop
Published: February 2023

First described in the early 20th century, diurnal oscillations in stem cell proliferation exist in multiple internal epithelia, including in the gastrointestinal tract, and in the epidermis. In the mouse epidermis, 3- to 4-fold more stem cells are in S-phase during the night than during the day. More recent work showed that an intact circadian clock intrinsic to keratinocytes is required for these oscillations in epidermal stem cell proliferation. The circadian clock also regulates DNA excision repair and DNA damage in epidermal stem cells in response to ultraviolet B radiation. During skin inflammation, epidermal stem cell proliferation is increased and diurnal oscillations are suspended. Here we discuss possible reasons for the evolution of this stem cell phenomenon. We argue that the circadian clock coordinates intermediary metabolism and the cell cycle in epidermal stem cells to minimize the accumulation of DNA damage from metabolism-generated reactive oxygen species. Circadian disruption, common in modern society, leads to asynchrony between metabolism and the cell cycle, and we speculate this will lead to oxidative DNA damage, dysfunction of epidermal stem cells, and skin aging.
Impact and mitigation of sampling bias to determine viral spread: Evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations
Authors: Layan Maylis , Müller Nicola F , Dellicour Simon , De Maio Nicola , Bourhy Hervé , Cauchemez Simon , Baele Guy
Published: February 2023

Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (Bayesian structured coalescent approximation [BASTA] and marginal approximation of the structured coalescent [MASCOT]). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on the simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for the CTMC model. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for the CTMC model, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing the sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.
Supporting a Culture of Wellness: Examining the Utility of the Residency Program Community Well-Being Instrument in the Medical Training and Work Environment
Authors: Trockel Mickey , Fischer Avital
Published: February 2023

Physicians are experiencing symptoms of burnout at unprecedented rates. It is essential to assess programmatic factors contributing to physician burnout as actionable items for work climate improvement. Creation of an evidence base of strategies and methods to cultivate a culture of wellness requires iterative assessment, program development and implementation, and evaluation. To serve their function optimally, assessment tools need to be reliable, valid, and sensitive to change. In this Invited Commentary, the authors discuss Vermette and colleagues’ report on the Residency Community Well-Being (RCWB) instrument. The authors examine the utility of the RCWB, a novel, validated tool that quantifies the subjective community well-being of an individual residency program and has 3 subscales that measure key aspects of interpersonal interactions among residents, with emphasis on those within the program leadership sphere of influence. The commentary authors recommend further validation of the RCWB, but acknowledge the instrument is a useful contribution to currently available measures in the domains of community well-being, workplace climate, and culture of wellness. Workplace interventions focused on community well-being or culture of wellness are particularly salient ethical and educational priorities for medical training programs. Prioritizing community well-being will help nurture trainees as an investment in the future of medical care, rather than an exploitable resource valued primarily for short-term work demands.
An Overview of This Year’s Trainee-Authored Letters to the Editor
Authors: Forrest Lala L. , Blyton Laura
Published: February 2023

Academic Medicine’s call for trainee-authored letters to the editor, which has occurred annually since 2016, has successfully provided a forum for collecting and amplifying trainee perspectives. In the latest call in 2022, trainees shared a transformative moment that occurred during their educational journey and how it shaped their identity as a health professional. In this Commentary, 2 members of the journal’s staff provide a brief retrospective of the annual call using key demographics of published letters and letter writers. The authors then delve into the published letters from the 2022 call. To showcase the myriad of transformations described, they conceptualize 3 themes that best characterize these special moments: (1) reshaping the trainee experience through advocacy; (2) exploring humanism, morals, and relationality; and (3) finding one’s mark within medicine. In addition, to display the depth and richness of transformative moments, the authors include an in-depth analysis of the letters by sampling those that were identified to each theme. In this overview, they hope to present readers with inspiration from trainees around the globe and invite them to reflect on and identify the significant experiences encountered in their own educational journey that altered their professional identity.
Predicting axial length in patients with Marfan syndrome and ectopia lentis after modified capsular tension ring and intraocular lens implantation
Authors: Chen Ze-Xu , Jia Wan-Nan , Ma Yong , Chen Tian-Hui , Hong Jia-Hao , Sun Yang , Liu Yan , Song Ling-Hao , Jiang Yong-Xiang
Published: February 2023

Purpose:

To predict the growth of axial length (AL) in patients with Marfan syndrome (MFS) and ectopia lentis (EL).

Setting:

Eye and ENT Hospital of Fudan University, Shanghai, China.

Design:

Consecutive retrospective case series.

Methods:

Eyes were evaluated that had modified capsular tension ring and intraocular lens (IOL) implantation. The rate of AL growth (RALG) was calculated using AL divided by log10-transformed age. A multivariate linear regression model of RALG was developed after validation.

Results:

128 patients with MFS and EL were enrolled with a median follow-up duration of about 3 years. RALG was independent of age between 3 years and 15 years old (P = .799) and decreased to 0 thereafter (P = .878). Preoperative AL was associated with RALG in patients under 15 years old (P = .003). Beta values for the final model of RALG were as below: intercept (−9.794) and preoperative AL (0.664). The postoperative AL was predicted as: postAL = preAL + RALG × log10 ([postAge + 0.6]/[preAge + 0.6]). The mean prediction error was −0.003 (95% CI, −0.386 to 0.3791) mm and the mean absolute percentage error was 1.93% (95% CI, 0.73% to 3.14%). A Python-based calculator was developed to use the predicted AL in selecting IOL power and setting undercorrection.

Conclusions:

The AL growth of patients with MFS followed a logarithmic pattern and ceased at about age 15. A prediction model of postoperative AL was established for individual MFS patients between 3 and 15 years old, which could potentially optimize the IOL power selection.
Anterior vitreous detachment and retrolental material during cataract surgery: incidence and risk factors, with pathological evidence
Authors: Lin Wenli , Luo Jiawei , Li Pengfei , Ji Min , Guan Huaijin
Published: February 2023

Purpose:

To determine the incidence of anterior vitreous detachment (AVD) and retrolental material occurrence in cataract surgery, determine the influence of surgical factors on it, and confirm the source of the material.

Setting:

Affiliated Hospital of Nantong University, Jiangsu Province, China.

Design:

Prospective single-center study.

Methods:

Age, sex, ocular complication, nuclear sclerosis grade, ultrasonic time, mean longitudinal power, cumulative dissipated energy (CDE), total aspiration time, and estimated fluid usage were recorded for each patient. Retrolental anatomy was observed before and during surgery using real-time optical coherence tomography integrated into a microscope. The eyes with AVD were carefully observed and recorded during illumination with an optical fiber. Retrolental material was stained using immunohistochemistry.

Results:

205 eyes from 205 patients were included in this study. Spontaneous AVD was found in 5 cases. Intraoperatively, AVD was identified in 115 eyes (56.1%). Retrolental material presence was observed in 75 eyes (36.6%). A logistic regression model showed that CDE and aspiration time had a statistically significant effect on AVD (P < .05, 95% CI, 1.011-1.558; P < .05, 95% CI, 1.026-1.051), and CDE was positively correlated with retrolental material occurrence (P < .05, 95% CI, 1.052-1.534). Samples from 5 cases expressed large amounts of αA- and βA-crystallins.

Conclusions:

Spontaneous AVD is rare in phakic eyes. There was a marked increase in AVD during surgery, with retrolental material occurring in more than a third of cases. Higher CDE and longer total aspiration time were risk factors for AVD. Immunohistochemistry revealed that most of the retrolental materials were lens fragments.
Challenges, Job Satisfiers, and Self-Care among Perinatal Nurses in the United States during the COVID-19 Pandemic
Authors: Iobst Stacey E. , Breman Rachel Blankstein , Walker Mark , Wysong Grace , Best Natasha , Edmonds Joyce K.
Published: February 2023

Purpose:

To explore the perceived challenges, job satisfiers, and self-care of perinatal nurses in the United States during the COVID-19 pandemic.

Study Design and Methods:

In May of 2021, a cross-sectional survey was distributed online to members of the Association of Women's Health, Obstetric, and Neonatal Nurses and the National Association of Neonatal Nurses. We calculated descriptive statistics on respondent characteristics and applied conventional content analysis to free-text comments.

Results:

Perinatal nurses (N = 297) responded to three open-ended questions on their perceived challenges, job satisfiers, and self-care. Frequently reported challenges included changing guidelines and policies (n = 101, 34%), personal protective equipment as a barrier (n = 73, 24.6%), and visitor restrictions (n = 64, 21.5%). Frequently reported job satisfiers were provision of high-quality care (n = 137, 46.1%) and visitor restrictions (n = 77, 25.9%). Respondents reported using mental (n = 152, 51.2%) and physical (n = 145, 48.8%) self-care strategies and 12.8% (n = 38) reported using no self-care strategies.

Clinical Implications:

The ability to provide high-quality care was reported as a leading job satisfier. Poor communication of consistent, evidence-based guidelines, lack of personal protective equipment, and inadequate unit staffing were leading challenges. Visitor restrictions were a challenge and a job satisfier, suggesting opportunities to better include visitors as support people. Most respondents reported engaging in one or more types of self-care outside of the hospital setting. Future research is needed to examine strategies for self-care among perinatal nurses when at work in the hospital setting.
Forest health in the Anthropocene: the emergence of a novel tree disease is associated with poplar cultivation
Authors: Feau Nicolas , Dhillon Braham D. , Sakalidis Monique , Dale Angela L. , Søndreli Kelsey L. , Goodwin Stephen B. , LeBoldus Jared M. , Hamelin Richard C.
Published: February 2023

Plant domestication and movement are large contributors to the success of new diseases. The introduction of new host species can result in accelerated evolutionary changes in pathogens, affecting long-established coevolutionary dynamics. This has been observed in poplars where severe epidemics of pathogens that were innocuous in their natural pathosystems occurred following host domestication. The North American fungus
Sphaerulina musiva
is responsible for endemic leaf spots on
Populus deltoides.
We show that the expansion of poplar cultivation resulted in the emergence of a new lineage of this pathogen that causes stem infections on a new host,
P. balsamifera
. This suggests a host shift since this is not a known host. Genome analysis of this emerging lineage reveals a mosaic pattern with islands of diversity separated by fixed genome regions, which is consistent with a homoploid hybridization event between two individuals that produced a hybrid swarm. Genome regions of extreme divergence and low diversity are enriched in genes involved in host–pathogen interactions. The specialization of this emerging lineage to a new host and its clonal propagation represents a serious threat to poplars and could affect both natural and planted forests. This work provides a clear example of the changes created by the intensification of tree cultivation that facilitate the emergence of specialized pathogens, jeopardizing the natural equilibrium between hosts and pathogens.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Polystyrene nanoplastics differentially influence the outcome of infection by two microparasites of the host
Daphnia magna
Authors: Manzi Florent , Schlösser Paula , Owczarz Agata , Wolinska Justyna
Published: February 2023

The accumulation of micro- and nanoplastic particles in freshwater bodies has given rise to much concern regarding their potential adverse effects on aquatic biota. Beyond their known effects on single species, recent experimental evidence suggests that host–parasite interactions can also be affected by environmental concentrations of micro- and nanoplastics. However, investigating the effects of contaminants in simplified infection settings (i.e. one host, one parasite) may understate their ecological relevance, considering that co-infections are common in nature. We exposed the cladoceran
Daphnia magna
to a fungal parasite of the haemolymph (
Metschnikowia bicuspidata
) and a gut microsporidium (
Ordospora colligata
), either in single or co-infection. In addition,
Daphnia
were raised individually in culture media containing 0, 5 or 50 mg l
−1
of polystyrene nanoplastic beads (100 nm). Only few infections were successful at the higher nanoplastic concentration, due to increased mortality of the host. While no significant effect of the low concentration was detected on the microsporidium, the proportion of hosts infected by the fungal parasite increased dramatically, leading to more frequent co-infections under nanoplastic exposure. These results indicate that nanoplastics can affect the performance of distinct pathogens in diverging ways, with the potential to favour parasite coexistence in a common zooplanktonic host.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Deeper habitats and cooler temperatures moderate a climate-driven seagrass disease
Authors: Graham Olivia J. , Stephens Tiffany , Rappazzo Brendan , Klohmann Corinne , Dayal Sukanya , Adamczyk Emily M. , Olson Angeleen , Hessing-Lewis Margot , Eisenlord Morgan , Yang Bo , Burge Colleen , Gomes Carla P. , Harvell Drew
Published: February 2023

Eelgrass creates critical coastal habitats worldwide and fulfills essential ecosystem functions as a foundation seagrass. Climate warming and disease threaten eelgrass, causing mass mortalities and cascading ecological impacts. Subtidal meadows are deeper than intertidal and may also provide refuge from the temperature-sensitive seagrass wasting disease. From cross-boundary surveys of 5761 eelgrass leaves from Alaska to Washington and assisted with a machine-language algorithm, we measured outbreak conditions. Across summers 2017 and 2018, disease prevalence was 16% lower for subtidal than intertidal leaves; in both tidal zones, disease risk was lower for plants in cooler conditions. Even in subtidal meadows, which are more environmentally stable and sheltered from temperature and other stressors common for intertidal eelgrass, we observed high disease levels, with half of the sites exceeding 50% prevalence. Models predicted reduced disease prevalence and severity under cooler conditions, confirming a strong interaction between disease and temperature. At both tidal zones, prevalence was lower in more dense eelgrass meadows, suggesting disease is suppressed in healthy, higher density meadows. These results underscore the value of subtidal eelgrass and meadows in cooler locations as refugia, indicate that cooling can suppress disease, and have implications for eelgrass conservation and management under future climate change scenarios.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Rising Cholera Cases in Pakistan: A Major Health Challenge due to Devastating Flood
Authors: Khan Ayesha , Siddiqui Fariha Masood
Published: February 2023

The health system of Pakistan has multiple threats like political instability, recession, disparitiesin access to health services, infrastructure, development challenges, emergence of COVID-19pandemic. Beginning of 2022 was marked with unusual surge in cholera cases. According toNational Institute of Health (NIH), Islamabad, varied number of suspected cholera cases werereported across four provinces. Floods hit the country in mid-July which further aggravated thesituation of healthcare services. Ministry of Health along with World Health Organization(WHO) need to implement preventive and supporting actions to control cholera and otherwaterborne diseases.
Methionyl-tRNA formyltransferase utilizes 10-formyldihydrofolate as an alternative substrate and impacts antifolate drug action
Authors: Sah Shivjee , Varshney Umesh
Published: February 2023

Methionyl-tRNA formyltransferase (Fmt)-mediated formylation of Met-tRNAfMet to fMet-tRNAfMet is crucial for efficient initiation of translation in bacteria and the eukaryotic organelles. Folate dehydrogenase-cyclohydrolase (FolD), a bifunctional enzyme, carries out conversion of 5,10-methylene tetrahydrofolate (5,10-CH2-THF) to 10-formyl-THF (10-CHO-THF), a metabolite utilized by Fmt as a formyl group donor. In this study, using in vivo and in vitro approaches, we show that 10-CHO-DHF may also be utilized by Fmt as an alternative substrate (formyl group donor) to formylate Met-tRNAfMet. Dihydrofolate (DHF) formed as a by-product in the in vitro assay was verified by LC-MS/MS analysis. FolD-deficient mutants and Fmt over-expressing strains were more sensitive to trimethoprim (TMP) than the ∆fmt strain, suggesting that the domino effect of TMP leads to inhibition of protein synthesis and strain growth. Antifolate treatment to

Escherichia coli

showed a decrease in the reduced folate species (THF, 5,10-CH2-THF, 5-CH3-THF, 5,10-CH+-THF and 5-CHO-THF) and increase in the oxidized folate species (folic acid and DHF). In cells, 10-CHO-DHF and 10-CHO-folic acid were enriched in the stationary phase. This suggests that 10-CHO-DHF is a bioactive metabolite in the folate pathway for generating other folate intermediates and fMet-tRNAfMet.
The role of folate receptor α in the partial rejuvenation of dentate gyrus cells. Improvement of cognitive function in elderly mice
Authors: Antón-Fernández A , Cuadros R , Peinado-Cahuchola R , Hernández F , Avila J
Published: February 2023

In this work, we have studied the effect of small compounds in the partial rejuvenation of dentate gyrus cells by measuring the improvement of cognitive functions in elderly mice.

Aging has been related to a change in DNA methylation and some one-carbon metabolites linked to that methylation process, like vitamin B12, folate or methionine have been involved in cognitive performance during aging. However, their role in this process and the possible mechanisms behind its cognitive effects are still unclear. Through direct infusion of these molecules in the dentate gyrus we have tested their effects on cognition in elderly mice. Only positive results were found for folate. A partial rejuvenation of dentate gyrus cells related to an increase in neuroplasticity by reorganizing extracellular matrix structures and rising the expression of juvenile genes like GluN2B was found. Since folate is involved in several cellular pathways in addition to DNA methylation, we have focused in its interaction with its folate receptor alpha (FRα), a protein that is present at the cell nucleus, acting as transcription factor. We have found that most of folate effects on brain would be mediated by the activation of FRα. In addition, we propose that the mechanism for cell rejuvenation by folate, or other FRα binding molecules, may involve the expression of proteins, like SOX2, a Yamanaka factor present in young neurons. Thus, the use of molecules that activate the FRα pathway could constitute an interesting strategy to be considered for the study of brain rejuvenation.
Development of a multifunctional toolkit of intrabody-based biosensors recognizing the V5 peptide tag: highlighting applications with G protein-coupled receptors
Authors: Zeghal Manel , Matte Kevin , Venes Angelica , Patel Shivani , Laroche Geneviève , Sarvan Sabina , Joshi Monika , Couture Jean-François , Giguère Patrick M.
Published: February 2023

ABSTRACT/SUMMARY

Protein-protein interactions (PPIs) form the underpinnings of any cellular signaling network. PPIs are highly dynamic processes and often, cell-based assays can be essential for their study as they closely mimic the biological intricacies of cellular environments. Since no sole platform can perform all needed experiments to gain a thoroughly comprehensive understanding into these processes, developing a versatile toolkit is much needed to address this longstanding gap. The use of small peptide tags, such as the V5-tag, has been extensively used in biological and biomedical research, including labeling the C-termini of one of the largest human genome-wide open-reading frame collections. However, these small peptide tags have been primarily usedin vitroand lack thein vivotraceability and functionality of larger specialized tags. In this study, we combined structural studies and computer-aided maturation to generate an intracellular nanobody, interacting with the V5-tag. Suitable for assays commonly used to study protein-protein interactions, our nanobody has been applied herein to interrogate G protein-coupled receptor signalling. This novel serviceable intrabody is the cornerstone of a multipurpose intracellular nanobody-based biosensors toolkit, named iBodyV5, which will be available for the scientific community at large.
Genomic signatures of bottleneck and founder effects in dingoes
Authors: Kumar Manoharan , Conroy Gabriel , Ogbourne Steven , Cairns Kylie , Borburgh Liesbeth , Subramanian Sankar
Published: February 2023

Dingoes arrived in Australia during the mid-Holocene and are the native top-order terrestrial predator on the mainland and some offshore islands. Although dingoes subsequently spread across the continent, the initial founding population(s) could have been small. To investigate this hypothesis, we examined the potential signatures of bottlenecks and founder effects in dingoes by sequencing the whole genomes of three dingoes and also obtaining the genome data from nine additional dingoes and 56 canines, including wolves, village dogs and breed dogs, and examined the signatures of bottlenecks and founder effects. We found that the nucleotide diversity of dingoes was low, and 36% less than highly inbred breed dogs and 3.3 times lower than wolves. The number of runs of homozygosity (RoH) segments in dingoes was 1.6 to 4.7 times higher than in other canines. Whilst examining deleterious mutational load, we observed that dingoes carried elevated ratios of nonsynonymous-to-synonymous diversities, significantly higher numbers of homozygous deleterious Single Nucleotide Variants (SNVs), and increased numbers of loss of function SNVs, compared to breed dogs, village dogs, and wolves. These results suggest dingoes experienced a severe bottleneck, potentially caused by the limited number of founding individuals. While many studies observe less diversity and a higher number of deleterious mutations in domesticated populations compared to their wild relatives, we observed the opposite – .i.e. wild dingoes have lower diversity and a greater number of harmful mutations than domesticated dogs. Our findings can be explained by bottlenecks and founder effects during the establishment of dingoes on mainland Australia. These findings highlight the need for conservation-based management of dingoes and need for wildlife managers to be cognisant of these findings when considering the use of lethal control measures across the landscape.
Identification of key virus–prokaryote infection pairs that contribute to viral shunt in a freshwater lake
Authors: Shen Shang , Tominaga Kento , Tsuchiya Kenji , Matsuda Tomonari , Yoshida Takashi , Shimizu Yoshihisa
Published: February 2023

Viruses infect and kill productive prokaryotes in a density-or frequency-dependent manner and affect carbon cycling. However, the effects of the stratification transition, including the stratified and destratified periods, on the changes in prokaryotic/viral communities and the interactions among them remain unclear. We conducted a monthly survey of the surface and deep layers of a large and deep freshwater lake (Lake Biwa, Japan) for a year and analyzed the prokaryotic production and prokaryotic/viral metagenome. Our analysis (including 1 608 prokaryotes and 13 761 viruses) revealed that 19 prokaryotic species, accounting for ∼40% of total abundance, might be suppressed by viruses when prokaryotic production is higher. This suggests that a small proportion of prokaryotes contribute to a large amount of prokaryotic abundance, and these prokaryotes are infected and lysed by viruses, driving the viral shunt in the freshwater lake. Furthermore, we found that annual vertical mixing might yield a similar rate of community change between the surface and deep layers. This finding might be valuable in understanding how the communities change when the stratification of freshwater lakes is affected by global warming in the future.
Ketamine evoked disruption of entorhinal and hippocampal spatial maps
Authors: Masuda Francis Kei , Sun Yanjun , Jones Emily A Aery , Giocomo Lisa M
Published: February 2023

Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine’s impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal’s spatial position, as mice navigated virtual reality and real world environments. Ketamine induced an acute disruption and long-term re-organization of entorhinal spatial representations. This acute ketamine-induced disruption reflected increased excitatory neuron firing rates and degradation of cell-pair temporal firing rate relationships. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings point to disruption in the spatial coding properties of the entorhinal-hippocampal circuit as a potential neural substrate for ketamine-induced changes in spatial cognition.