bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRECOGx: exploring GPCR signaling mechanisms with deep protein representations
Authors: Matic Marin , Singh Gurdeep , Carli Francesco , De Oliveira Rosa Natalia , Miglionico Pasquale , Magni Lorenzo , Gutkind J Silvio , Russell Robert B , Inoue Asuka , Raimondi Francesco 
Published: May 2022

Abstract
In this study we show that protein language models can encode structural and functional information of GPCR sequences that can be used to predict their signaling and functional repertoire. We used the ESM1b protein embeddings as features and the binding information known from publicly available studies to develop PRECOGx, a machine learning predictor to explore GPCR interactions with G protein and β-arrestin, which we made available through a new webserver (https://precogx.bioinfolab.sns.it/). PRECOGx outperformed its predecessor (e.g. PRECOG) in predicting GPCR-transducer couplings, being also able to consider all GPCR classes. The webserver also provides new functionalities, such as the projection of input sequences on a low-dimensional space describing essential features of the human GPCRome, which is used as a reference to track GPCR variants. Additionally, it allows inspection of the sequence and structural determinants responsible for coupling via the analysis of the most important attention maps used by the models as well as through predicted intramolecular contacts. We demonstrate applications of PRECOGx by predicting the impact of disease variants (ClinVar) and alternative splice forms from healthy tissues (GTEX) of human GPCRs, revealing the power to dissect system biasing mechanisms in both health and disease.
Structural basis of transcription activation by Rob, a pleiotropic AraC/XylS family regulator
Authors: Shi Jing , Wang Fulin , Li Fangfang , Wang Lu , Xiong Ying , Wen Aijia , Jin Yuanling , Jin Sha , Gao Fei , Feng Zhenzhen , Li Jiacong , Zhang Yu , Shang Zhuo , Wang Shuang , Feng Yu , Lin Wei 
Published: May 2022

Abstract
Rob, which serves as a paradigm of the large AraC/XylS family transcription activators, regulates diverse subsets of genes involved in multidrug resistance and stress response. However, the underlying mechanism of how it engages bacterial RNA polymerase and promoter DNA to finely respond to environmental stimuli is still elusive. Here, we present two cryo-EM structures of Rob-dependent transcription activation complex (Rob-TAC) comprising of Escherichia coli RNA polymerase (RNAP), Rob-regulated promoter and Rob in alternative conformations. The structures show that a single Rob engages RNAP by interacting with RNAP αCTD and σ70R4, revealing their generally important regulatory roles. Notably, by occluding σ70R4 from binding to -35 element, Rob specifically binds to the conserved Rob binding box through its consensus HTH motifs, and retains DNA bending by aid of the accessory acidic loop. More strikingly, our ligand docking and biochemical analysis demonstrate that the large Rob C-terminal domain (Rob CTD) shares great structural similarity with the global Gyrl-like domains in effector binding and allosteric regulation, and coordinately promotes formation of competent Rob-TAC. Altogether, our structural and biochemical data highlight the detailed molecular mechanism of Rob-dependent transcription activation, and provide favorable evidences for understanding the physiological roles of the other AraC/XylS-family transcription factors.
Advancing Grain Legumes Domestication and Evolution Studies with Genomics
Authors: Zhang Hailin , Mascher Martin , Abbo Shahal , Jayakodi Murukarthick 
Published: May 2022

Abstract
Grain legumes were domesticated in parallel with cereals in several regions of the world and formed the economic basis of early farming cultures. Since then, legumes have played a vital role in human and animal diets and in fostering agrobiodiversity. Increasing grain legume cultivation will be crucial to safeguard nutritional security and the resilience of agricultural ecosystems across the globe. A better understanding of the molecular underpinnings of domestication and crop evolution of grain legumes may be translated into practical approaches in modern breeding programs to stabilize yield, which is threatened by evolving pathogens and changing climates. During recent decades, domestication research in all crops has greatly benefited from the fast progress in genomic technologies. Yet still, many questions surrounding the domestication and diversification of legumes remain unanswered. In this review, we assess the potential of genomic approaches in grain legume research. We describe the centers of origin and the crucial domestication traits of grain legumes. In addition, we survey the effect of domestication on both above-ground and below-ground traits that have economic importance. Finally, we discuss open questions in grain legume domestication and diversification and outline how to bridge the gap between the preservation of historic crop diversity and their utilization in modern plant breeding.
MECHANISMS OF RADIATION CARCINOGENESIS: WHAT IS REALLY INDUCED?
Authors: Nakamura Nori 
Published: May 2022

Abstract
It has been difficult to understand why the relative risk for cancer decreases with an increase in time since an exposure to radiation. It was recently recognized that this decline can be explained by a parallel shift of the age-related cancer mortality curve toward younger ages. In fact, it has been known for many years that mouse survival curves exhibit a parallel shift toward younger ages following an exposure to radiation, but it was not recognized that the mutation induction theory is incompatible with this parallel shift. This is because a parallel shift in the survival curve implies that all the irradiated individuals are affected, but the mutation induction theory assumes that only a fraction of the irradiated individuals is affected following an exposure to radiation. Thus, it seems likely that the target of radiation action, which leads to carcinogenesis, is not restricted to epithelial cells but includes all of the surrounding cells leading to an altered microenvironment. Since it is repeatedly observed that radiation-exposed normal tissues can stimulate transplanted or spontaneously arising tumor cells to grow faster, worsen the malignant phenotypes and finally kill the host earlier than usual, an exposure to radiation seems most likely to cause tissue inflammation, which creates conditions favorable for the growth of spontaneously arising tumor cells. This new concept suggests that it might be possible to attenuate the extent of radiation carcinogenesis by intervening in tissue inflammatory processes.
Sleep disturbances among women in a Subarctic region: a nationwide study
Authors: Unnarsdóttir Anna Bára , Hauksdóttir Arna , Aspelund Thor , Gunnarsdóttir Vigdís , Tómasson Gunnar , Jakobsdóttir Jóhanna , Valdimarsdóttir Unnur Anna , Thordardottir Edda Bjork 
Published: May 2022

Abstract

Study Objectives
To date, few studies have assessed sleep problems among women residing in Subarctic regions. Therefore, the aim of this large-scale population-based study was to assess the prevalence of severe sleep problems and associated factors among Icelandic women, living at 63–66°N.

Methods
Participants were 29 681 women (18–69 years old) who took part in the Icelandic Stress-And-Gene-Analysis study in 2018–2019. Background information, health-related behavior, and mental health symptoms were assessed with an online questionnaire. The Pittsburgh Sleep Quality Index (PSQI) was used to assess severe sleep problems during the past month. Adjusting for age, marital status, number of children, education, personal income, work schedule, region, and response period, we used modified Poisson log-linear models to obtain prevalence ratios (PRs) with 95% confidence intervals (CIs).

Results
Overall, 24.2% of women reported severe sleep problems (PSQI &gt;10). Women responding in the winter presented with an overall higher prevalence of severe sleep problems, compared to those responding in the summer (PR 1.21; 95% CI, 1.15 to 1.28). Severe sleep problems were more prevalent among young and late-midlife women, those who were single, had children, socio-economic challenges, worked shifts, and flexible hours. Furthermore, obesity, suboptimal health behaviors, excessive screen time, and mental health problems were associated with severe sleep problems.

Conclusion
Severe sleep problems are more common among women in Subarctic regions than elsewhere, particularly during winter. These findings motivate the development of preventive strategies and interventions for women in the Subarctic who suffer from sleep problems.
Discovery of a new scale worm (Annelida: Polynoidae) with presumed deep-sea affinities from an anchialine cave in the Balearic Islands (western Mediterranean)
Authors: Capa María , Pons Joan , Jaume Damià 
Published: May 2022

Abstract
A remarkable new genus and species of scale worm (Annelida: Polynoidae) was found on the bottom sediments of an anchialine cave on the island of Mallorca (Balearic Islands, western Mediterranean). Specimens reach up to 2 cm long, lack eyes and body pigmentation except for a few scattered minute speckles and show enlarged parapodia and sensorial appendages. A red brain is visible through the translucent tegument. Morphological features resemble those of Eulagiscinae, currently comprising eight species in three genera. Phylogenetic analyses of mitochondrial and nuclear DNA sequences are not conclusive on the position of the new taxon but affinity to Eulagiscinae is not ruled out, particularly when taxa with missing data or non-homologous insertion sites are excluded from the analyses. Pollentia perezi gen. & sp. nov. is characterized by a unique set of morphological features: 13 pairs of dorsal elytra; a single type of notochaetae (stout, with spinous rows and pointed tip); and two types of neurochaetae (superior flattened, spinous with tridentate tip; inferior shorter and thinner, lanceolate and pectinate). Some characteristics, such as the long parapodial appendages and swimming habits, are shared with other cave scale worms. However, the new taxon is not closely related to the other two known cave-dwelling polynoids.
Limited Effect of Perioperative Systemic Therapy in Patients Selected for Repeat Local Treatment of Recurrent Colorectal Cancer Liver Metastases
Authors: Hellingman Tessa , Galjart Boris , Henneman Julia J. , Görgec Burak , Bijlstra Okker D. , Meijerink Martijn R. , Vahrmeijer Alexander L. , Grünhagen Dirk J. , van der Vliet Hans J. , Swijnenburg Rutger-Jan , Verhoef Cornelis , Kazemier Geert 
Published: May 2022

Objectives:
The aim of this study was to determine the potential benefit of perioperative systemic therapy on overall and progression-free survival after repeat local treatment in patients suffering from recurrent colorectal cancer liver metastasis (CRLM).

Background:
The optimal treatment strategy in patients with recurrent CRLM needs to be clarified, in particular for those suffering from early recurrence of CRLM.

Methods:
In this multicenter observational cohort study, consecutive patients diagnosed with recurrent CRLM between 2009 and 2019 were retrospectively identified in 4 academic liver surgery centers. Disease-free interval after initial local treatment of CRLM was categorized into recurrence within 6, between 6 and 12, and after 12 months. Perioperative systemic therapy consisted of induction, (neo)adjuvant, or combined regimens. Overall and progression-free survival after repeat local treatment of CRLM were analyzed by multivariable Cox regression analyses, resulting in adjusted hazard ratios (aHRs).

Results:
Out of 303 patients included for analysis, 90 patients received perioperative systemic therapy for recurrent CRLM. Favorable overall (aHR, 0.45; 95% confidence interval [CI], 0.26–0.75) and progression-free (aHR, 0.53; 95% CI, 0.35–0.78) survival were observed in patients with a disease-free interval of more than 12 months. No significant difference in overall and progression-free survival was observed in patients receiving perioperative systemic therapy at repeat local treatment of CRLM, stratified for disease-free interval, previous exposure to chemotherapy, and RAS mutation status.

Conclusions:
No benefit of perioperative systemic therapy was observed in overall and progression-free survival after repeat local treatment of recurrent CRLM.
Improving Post-Injury Care: Key Family Caregiver Perspectives of Critical Illness After Injury
Authors: Ross Perfetti Angela , Jacoby Sara F. , Buddai Sruthi , Kaplan Lewis J. , Lane-Fall Meghan 
Published: May 2022

BACKGROUND:
There is little research about how caregiver experiences evolve from ICU admission to patient recovery, especially among caregivers for patients who have traumatic injuries. In this study, we characterize diverse caregiver experiences during and after ICU admission for injury.

METHODS:
This prospective observational study is based in a level 1 trauma center in Philadelphia, Pennsylvania. Longitudinal interviews among caregivers of patients who required ICU admission for traumatic injury were conducted from the time of ICU admission to 12 months after hospital discharge. Transcripts were analyzed using a qualitative descriptive approach.

RESULTS:
Sixty-five interviews were conducted with 19 caregivers. The interview results converged on four areas: experiences in the ICU, the aftermath of violent traumatic injury, caregiver responsibilities, and care in the context of the wider family. In the ICU, caregivers contended with worry and uncertainty, and they often hid these feelings. Many felt that they always needed to be at the bedside, leading to stress and exhaustion. Caregivers had difficulty communicating with their loved ones, and communication itself sometimes became a source of conflict. Over time, caregivers were burdened by many managerial responsibilities. In addition, violent traumatic injury caused an overlay of concern for patients’ safety. The need to plan for recovery caused caregivers to make substantial sacrifices. As a result of these difficult experiences, some caregivers and patients drew closer together, while others were divided by conflict.

CONCLUSIONS:
Illness after traumatic injury may be devastating for caregivers, disrupting emotional wellbeing and other aspects of life. Caregivers are variably prepared for the challenges of ICU care and caregiving through convalescence and require robust support during and after ICU admission to enable effective communication, resource access, and an ongoing relationship with the healthcare team.
Nebulized Amphotericin B in Mechanically Ventilated COVID-19 Patients to Prevent Invasive Pulmonary Aspergillosis: A Retrospective Cohort Study
Authors: Melchers Max , van Zanten Arthur R. H. , Heusinkveld Moniek , Leeuwis Jan Willem , Schellaars Roel , Lammers Hendrick J. W. , Kreemer Freek J. , Haas Pieter-Jan , Verweij Paul E. , van Bree Sjoerd H. W. 
Published: May 2022

IMPORTANCE:
Despite high mortality rates of COVID-19-associated pulmonary aspergillosis (CAPA) in the ICU, antifungal prophylaxis remains a subject of debate. We initiated nebulized conventional amphotericin B (c-AmB) as antifungal prophylaxis in COVID-19 patients on invasive mechanical ventilation (IMV).

OBJECTIVES:
To assess the CAPA incidence in COVID-19 patients on IMV treated with and without nebulized c-AmB as antifungal prophylaxis.

DESIGN, SETTING, AND PARTICIPANTS:
Retrospective cohort study of consecutive COVID-19 patients admitted to our adult 17-bed ICU in a university-affiliated general hospital in Ede, The Netherlands, between January 25, 2021, and July 9, 2021. Patients not requiring IMV or transferred from or to another ICU were excluded. From April 9, 2021, daily nebulized amphotericin B in all patients on IMV was initiated.

MAIN OUTCOMES AND MEASURES:
Bronchoscopy with bronchoalveolar lavage (BAL) was performed in case of positive cultures for Aspergillus from the respiratory tract and/or unexplained respiratory deterioration. Incidence of probable and proven CAPA was compared between patients treated with and without nebulized antifungal prophylaxis using Pearson chi-square test.

RESULTS:
A total of 39 intubated COVID-19 patients could be analyzed, of which 16 were treated with antifungal prophylaxis and 23 were not. Twenty-six patients underwent bronchoscopy with BAL. In patients treated with antifungal prophylaxis, the incidence of probable/proven CAPA was significantly lower when compared with no antifungal prophylaxis (27% vs 67%; p = 0.047). Incidence of tracheobronchial lesions and positive Aspergillus cultures and BAL-galactomannan was significantly lower in patients treated with antifungal prophylaxis (9% vs 47%; p = 0.040, 9% vs 53%; p = 0.044, and 20% vs 60%; p = 0.047, respectively). No treatment-related adverse events and no case of proven CAPA were encountered in patients receiving antifungal prophylaxis.

CONCLUSIONS AND RELEVANCE:
Nebulization of c-AmB in critically ill COVID-19 patients on IMV is safe and may be considered as antifungal prophylaxis to prevent CAPA. However, a randomized controlled trial to confirm this is warranted.
Immediate Lymphatic Reconstruction during Axillary Node Dissection for Breast Cancer: A Systematic Review and Meta-analysis
Authors: Hill W. K. Fraser , Deban Melina , Platt Alexander , Rojas-Garcia Priscilla , Jost Evan , Temple-Oberle Claire 
Published: May 2022

Background:
The objective of this study is to summarize the current body of evidence detailing the impact of immediate lymphatic reconstruction (ILR) on the incidence of breast cancer-related lymphedema (BCRL) following axillary node dissection (ALND).

Methods:
Medline and Embase databases were queried for publications, where ILR was performed at the time of ALND for breast cancer. Exclusion criteria included lymphaticovenous anastomosis for established BCRL, animal studies, non-breast cancer patient population studies, and descriptive studies detailing surgical technique. Meta-analysis was performed with a forest plot generated using a Mantel -Haenszel statistical method, with a random-effect analysis model. Effect measure was reported as risk ratios with associated 95% confidence intervals. The risk of bias within studies was assessed by the Cochrane Collaboration tool.

Results:
This systematic review yielded data from 11 studies and 417 breast cancer patients who underwent ILR surgery at the time of ALND. There were 24 of 417 (5.7%) patients who developed BCRL following ILR. Meta-analysis revealed that in the ILR group, 6 of 90 patients (6.7%) developed lymphedema, whereas in the control group, 17 of 50 patients (34%) developed lymphedema. Patients in the ILR group had a risk ratio of 0.22 (CI, 0.09 -0.52) of lymphedema with a number needed to treat of four.

Conclusions:
There is a clear signal indicating the benefit of ILR in preventing BCRL. Randomized control trials are underway to validate these findings. ILR may prove to be a beneficial intervention for improving the quality of life of breast cancer survivors.
A Scoping Review of the Incidence, Predictors, and Outcomes of Delirium Among Critically Ill Stroke Patients
Authors: Lawson Thomas N. , Balas Michele C. , McNett Molly 
Published: May 2022

ABSTRACT

BACKGROUND: Delirium is a common, often iatrogenically induced syndrome that may impede the physical, cognitive, and psychological recovery of critically ill adults. The effect delirium has on outcomes of intensive care unit patients having acute neurologic injury remains unclear because previous studies frequently exclude this vulnerable population. The aim of this scoping review was to describe the incidence, predictors, and outcomes of delirium among adults admitted to an intensive care unit experiencing an acute ischemic stroke, intracerebral hemorrhage, or aneurysmal subarachnoid hemorrhage. METHODS: PubMed, CINAHL, Web of Science, EMBASE, and Scopus were searched with the terms (1) stroke, (2) critical care, and (3) delirium. Inclusion criteria were original peer-reviewed research reporting the incidence, outcomes, or predictors of delirium after acute stroke among critically ill adults. Editorials, reviews, posters, conference proceedings, abstracts, and studies in which stroke was not the primary reason for admission were excluded. Title and abstract screening, full-text review, and data extraction were performed by 2 authors, with disagreements adjudicated by a third author. RESULTS: The initial search yielded 1051 results. Eighteen studies met eligibility criteria and were included in the review. Stroke type was not mutually exclusive and included persons given a diagnosis of acute ischemic stroke (11), intracerebral hemorrhage (12), aneurysmal subarachnoid hemorrhage (8), and other (1) strokes. Incidence of delirium among stroke patients ranged from 12% to 75%. Predictors of delirium included older age, preexisting dementia, higher severity of illness, and physical restraint use. Outcomes associated with delirium included higher mortality, longer length of stay, worse cognition and quality of life, and lower functional status. CONCLUSIONS: Current findings are limited by heterogenous populations, assessments, and measurement parameters. Detection and management of delirium among critically ill stroke patients requires an approach with specific considerations to the complexities of acute neurological injury and concomitant critical illness.
The Association Between Sex and Osteoarthritis in the Physically Active Population: A Systematic Review
Authors: Migliorini Filippo , Torsiello Ernesto , La Padula Gerardo , Oliva Francesco , Maffulli Nicola 
Published: May 2022

Purpose:
Intense sporting activity and certain types of work increase the risk of early osteoarthritis (OA). OA can be idiopathic or associated to certain predisposing factors: female sex, obesity, history of joint injury, and joint overuse. The role of gender among the active population as a predisposing factor for OA is not well clear. This study investigated whether the risk of OA changes with age in both sexes in physically active individuals.

Materials and Methods:
This systematic review was conducted according to the PRISMA guidelines 2020. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in April 2021. No time constrains were used for the search. All the published clinical studies reporting data about relationship between physical activity and OA were included.

Results:
Data from 7 articles were retrieved including 360,053 patients (271,903 males; 88,150 females). The mean age was 48.2±16.7 years. Males, under the age of 60 had a higher risk of developing OA. People undertaking intense physical activity, such as professional athletes or heavy workers, are more prone to develop early OA.

Conclusion:
Physically active males demonstrated a higher risk of developing OA.