bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of fluorodeoxyglucose-positron emission tomography in predicting the pathological response and prognosis after neoadjuvant chemoradiotherapy for locally advanced non-small-cell lung cancer
Authors: Tanahashi Masayuki , Suzuki Eriko , Yoshii Naoko , Watanabe Takuya , Tsuchida Hiroyuki , Yobita Shogo , Iguchi Kensuke , Uchiyama Suiha , Nakamura Minori
Published: May 2022

OBJECTIVES

The present study compared the utility of fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) for predicting the pathological response and prognosis following neoadjuvant therapy for locally advanced non-small-cell lung cancer (NSCLC).

METHODS

This retrospective analysis included 72 patients in whom adjacent structures showed involvement and/or cN2 NSCLC who received induction chemoradiotherapy (ICRT) and subsequent surgery at our hospital from 2008 to 2019. FDG-PET and CT were performed in all patients before and after ICRT using the same scanner with similar techniques. We calculated the reduction in the maximum standardized uptake value in FDG-PET (ΔSUVmax) and tumour size on CT (ΔCT-size) before and after ICRT and investigated the relationship between the pathological response and prognosis.

RESULTS

The disease response was classified as a major pathological response in 43 patients, and a minor response in 29 patients. ΔSUVmax 60% and ΔCT-size 30% were identified as the optimal cut-off values for predicting a major pathological response. ΔSUVmax was superior to ΔCT-size in terms of sensitivity, specificity, positive predictive value and negative predictive value. Furthermore, ΔSUVmax was superior to ΔCT-size for predicting the prognosis.

CONCLUSIONS

Based on the results of the present study, FDG-PET appeared to have greater utility than CT in predicting the pathological response following ICRT and the postoperative prognosis in patients with locally advanced NSCLC.
The theory behind vessel length determination using gas flow rates and comparison between two pneumatic methods based on seven woody species
Authors: Peng Guoquan , Geng Hongru , Li Yaxin , Ren Zhiyang , Peng Juan , Cao Lei , Pereira Luciano , Tyree Melvin T , Yang Dongmei
Published: May 2022

In plants, xylem vessel length is important for long-distance water transport; however, the currently used methods for vessel length measurement are inconvenient and time-consuming. The recently developed semi-automated Pneumatron is a device based on the pneumatic theory that is similar to the air-injection method, and can rapidly estimate vessel length. Mean vessel length was compared between the Pneumatron and the air-injection method in seven woody species with a wide range of vessel lengths (2.3–78.7 cm). The results were consistent between the two methods, regardless of whether the same or different samples were used. The theory underlying the gas flow in vessels was improved and expanded, and compared to that underlying the water flow in order to better understand the pneumatic processes within a stem sample. Moreover, a new and simple equation for gas flow in vessels was derived based on the molar gas flow (mol s-1) rather than volume flow, because the former remains constant with distance throughout the stem axis. We strongly recommend using the Pneumatron in future studies owing to its low cost, convenience, rapidity, and simple operation. However, a number of potential issues need to be considered to avoid artifacts during measurements.
Nuclear movement in growing Arabidopsis root hairs involves both actin filaments and microtubules
Authors: Brueggeman Justin M , Windham Ian A , Nebenführ Andreas
Published: May 2022

Nuclear migration during growth and development is a conserved phenomenon among many eukaryotic species. In Arabidopsis, movement of the nucleus is important for root hair growth, but the detailed mechanism behind this movement is not well known. Previous studies in different cell types have reported that the myosin XI-I motor protein is responsible for this nuclear movement by attaching to the nuclear transmembrane protein complex WIT1/WIT2. Here, we analyzed nuclear movement in growing root hairs of wild-type, myosin xi-i, and wit1 wit2 Arabidopsis lines in the presence of actin and microtubule-disrupting inhibitors to determine the individual effects of actin filaments and microtubules on nuclear movement. We discovered that forward nuclear movement during root hair growth can occur in the absence of myosin XI-I, suggesting the presence of an alternative actin-based mechanism that mediates rapid nuclear displacements. By quantifying nuclear movements with high temporal resolution during the initial phase of inhibitor treatment, we determined that microtubules work to dampen erratic nuclear movements during root hair growth. We also observed microtubule-dependent backwards nuclear movement when actin filaments were impaired in the absence of myosin XI-I, indicating the presence of complex interactions between the cytoskeletal arrays during nuclear movements in growing root hairs.
Long-term instability of the inner Solar system: numerical experiments
Authors: Hoang Nam H , Mogavero Federico , Laskar Jacques
Published: May 2022

Apart from being chaotic, the inner planets in the Solar system constitute an open system, as they are forced by the regular long-term motion of the outer ones. No integrals of motion can bound a priori the stochastic wanderings in their high-dimensional phase space. Still, the probability of a dynamical instability is remarkably low over the next 5 billion years, a time-scale 1000 times longer than the Lyapunov time. The dynamical half-life of Mercury has indeed been estimated recently at 40 billion years. By means of the computer algebra system trip, we consider a set of dynamical models resulting from truncation of the forced secular dynamics recently proposed for the inner planets at different degrees in eccentricities and inclinations. Through ensembles of 103–105 numerical integrations spanning 5–100 Gyr, we find that the Hamiltonian truncated at degree 4 practically does not allow any instability over 5 Gyr. The destabilization is mainly due to terms of degree 6. This surprising result suggests an analogy to the Fermi–Pasta–Ulam–Tsingou problem, in which tangency to Toda Hamiltonian explains the very long time-scale of thermalization, which Fermi unsuccessfully looked for.
Dark matter cores in massive high-z galaxies formed by baryonic clumps
Authors: Ogiya Go , Nagai Daisuke
Published: May 2022

The rotation curves of some star-forming massive galaxies at redshift two decline over the radial range of a few times the effective radius, indicating a significant deficit of dark matter (DM) mass in the galaxy centre. The DM mass deficit is interpreted as the existence of a DM density core rather than the cuspy structure predicted by the standard cosmological model. A recent study proposed that a galaxy merger, in which the smaller satellite galaxy is significantly compacted by dissipative contraction of the galactic gas, can heat the centre of the host galaxy and help make a large DM core. By using an N-body simulation, we find that a large amount of DM mass is imported to the centre by the merging satellite, making this scenario an unlikely solution for the DM mass deficit. In this work, we consider giant baryonic clumps in high-redshift galaxies as alternative heating source for creating the baryon dominated galaxies with a DM core. Due to dynamical friction, the orbit of clumps decays in a few Gyr and the baryons condensate at the galactic centre. As a back-reaction, the halo centre is heated up and the density cusp is flattened out. The combination of the baryon condensation and core formation makes the galaxy baryon dominated in the central 2–5 kpc, comparable to the effective radius of the observed galaxies. Thus, the dynamical heating by giant baryonic clumps is a viable mechanism for explaining the observed dearth of DM in high redshift galaxies.
SubcellulaRVis: a web-based tool to simplify and visualise subcellular compartment enrichment
Authors: Watson Joanne , Smith Michael , Francavilla Chiara , Schwartz Jean-Marc
Published: May 2022

Cells contain intracellular compartments, including membrane-bound organelles and the nucleus, and are surrounded by a plasma membrane. Proteins are localised to one or more of these cellular compartments; the correct localisation of proteins is crucial for their correct processing and function. Moreover, proteins and the cellular processes they partake in are regulated by relocalisation in response to various cellular stimuli. High-throughput ‘omics experiments result in a list of proteins or genes of interest; one way in which their functional role can be understood is through the knowledge of their subcellular localisation, as deduced through statistical enrichment for Gene Ontology Cellular Component (GOCC) annotations or similar. We have designed a bioinformatics tool, named SubcellulaRVis, that compellingly visualises the results of GOCC enrichment for quick interpretation of the localisation of a group of proteins (rather than single proteins). We demonstrate that SubcellulaRVis precisely describes the subcellular localisation of gene lists whose locations have been previously ascertained. SubcellulaRVis can be accessed via the web (http://phenome.manchester.ac.uk/subcellular/) or as a stand-alone app (https://github.com/JoWatson2011/subcellularvis). SubcellulaRVis will be useful for experimental biologists with limited bioinformatics expertise who want to analyse data related to protein (re)localisation and location-specific modules within the intracellular protein network.
Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs
Authors: Patel Priyanka , Buchanan Courtney N , Zdradzinski Matthew D , Sahoo Pabitra K , Kar Amar N , Lee Seung Joon , Vaughn Lauren S , Urisman Anatoly , Oses-Prieto Juan , Dell’Orco Michela , Cassidy Devon E , Costa Irene Dalla , Miller Sharmina , Thames Elizabeth , Smith Terika P , Burlingame Alma L , Perrone-Bizzozero Nora , Twiss Jeffery L
Published: May 2022

Axonally synthesized proteins support nerve regeneration through retrograde signaling and local growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional regulation of neuronal mRNAs, but only a limited number of axonal RBPs are known. We used targeted proteomics to profile RBPs in peripheral nerve axons. We detected 76 proteins with reported RNA binding activity in axoplasm, and levels of several change with axon injury and regeneration. RBPs with altered levels include KHSRP that decreases neurite outgrowth in developing CNS neurons. Axonal KHSRP levels rapidly increase after injury remaining elevated up to 28 days post axotomy. Khsrp mRNA localizes into axons and the rapid increase in axonal KHSRP is through local translation of Khsrp mRNA in axons. KHSRP can bind to mRNAs with 3’UTR AU-rich elements and targets those transcripts to the cytoplasmic exosome for degradation. KHSRP knockout mice show increased axonal levels of KHSRP target mRNAs, Gap43, Snap25, and Fubp1, following sciatic nerve injury and these mice show accelerated nerve regeneration in vivo. Together, our data indicate that axonal translation of the RNA binding protein Khsrp mRNA following nerve injury serves to promote decay of other axonal mRNAs and slow axon regeneration.
DrugVirus.info 2.0: an integrative data portal for broad-spectrum antivirals (BSA) and BSA-containing drug combinations (BCCs)
Authors: Ianevski Aleksandr , Simonsen Ronja M , Myhre Vegard , Tenson Tanel , Oksenych Valentyn , Bjørås Magnar , Kainov Denis E
Published: May 2022

Viruses can cross species barriers and cause unpredictable outbreaks in man with substantial economic and public health burdens. Broad-spectrum antivirals, (BSAs, compounds inhibiting several human viruses), and BSA-containing drug combinations (BCCs) are deemed as immediate therapeutic options that fill the void between virus identification and vaccine development. Here, we present DrugVirus.info 2.0 (https://drugvirus.info), an integrative interactive portal for exploration and analysis of BSAs and BCCs, that greatly expands the database and functionality of DrugVirus.info 1.0 webserver. Through the data portal that now expands the spectrum of BSAs and provides information on BCCs, we developed two modules for (i) interactive analysis of users’ own antiviral drug and combination screening data and their comparison with published datasets, and (ii) exploration of the structure–activity relationship between various BSAs. The updated portal provides an essential toolbox for antiviral drug development and repurposing applications aiming to identify existing and novel treatments of emerging and re-emerging viral threats.
The C-terminal LCAR of host ANP32 proteins interacts with the influenza A virus nucleoprotein to promote the replication of the viral RNA genome
Authors: Wang Fangzheng , Sheppard Carol M , Mistry Bhakti , Staller Ecco , Barclay Wendy S , Grimes Jonathan M , Fodor Ervin , Fan Haitian
Published: May 2022

The segmented negative-sense RNA genome of influenza A virus is assembled into ribonucleoprotein complexes (RNP) with viral RNA-dependent RNA polymerase and nucleoprotein (NP). It is in the context of these RNPs that the polymerase transcribes and replicates viral RNA (vRNA). Host acidic nuclear phosphoprotein 32 (ANP32) family proteins play an essential role in vRNA replication by mediating the dimerization of the viral polymerase via their N-terminal leucine-rich repeat (LRR) domain. However, whether the C-terminal low-complexity acidic region (LCAR) plays a role in RNA synthesis remains unknown. Here, we report that the LCAR is required for viral genome replication during infection. Specifically, we show that the LCAR directly interacts with NP and this interaction is mutually exclusive with RNA. Furthermore, we show that the replication of a short vRNA-like template that can be replicated in the absence of NP is less sensitive to LCAR truncations compared with the replication of full-length vRNA segments which is NP-dependent. We propose a model in which the LCAR interacts with NP to promote NP recruitment to nascent RNA during influenza virus replication, ensuring the co-replicative assembly of RNA into RNPs.
Organization of gene programs revealed by unsupervised analysis of diverse gene–trait associations
Authors: Mizikovsky Dalia , Naval Sanchez Marina , Nefzger Christian M , Cuellar Partida Gabriel , Palpant Nathan J
Published: May 2022

Genome wide association studies provide statistical measures of gene–trait associations that reveal how genetic variation influences phenotypes. This study develops an unsupervised dimensionality reduction method called UnTANGLeD (Unsupervised Trait Analysis of Networks from Gene Level Data) which organizes 16,849 genes into discrete gene programs by measuring the statistical association between genetic variants and 1,393 diverse complex traits. UnTANGLeD reveals 173 gene clusters enriched for protein–protein interactions and highly distinct biological processes governing development, signalling, disease, and homeostasis. We identify diverse gene networks with robust interactions but not associated with known biological processes. Analysis of independent disease traits shows that UnTANGLeD gene clusters are conserved across all complex traits, providing a simple and powerful framework to predict novel gene candidates and programs influencing orthogonal disease phenotypes. Collectively, this study demonstrates that gene programs co-ordinately orchestrating cell functions can be identified without reliance on prior knowledge, providing a method for use in functional annotation, hypothesis generation, machine learning and prediction algorithms, and the interpretation of diverse genomic data.
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

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

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

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

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

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 >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

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.
Social Determinants of Health in Oncology
Authors: Venkataramany Barat S. , Sutton Jeffrey M.
Published: May 2022

Social determinants of health (SDOH) are defined as the set of modifiable social and physical risk factors that affect health. It is known that SDOH directly influence the population’s overall health, but their effects on patients with cancer are considerably less elucidated. Here, we review the literature describing the effects of SDOH outlined by the Healthy People 2020 framework on patients diagnosed with cancer. We have found that while some SDOH are well-defined in cancer patients, evidence surrounding several variables is scarce. In addition, we have found that many SDOH are associated with disparities at the screening stage, indicating that upstream interventions are necessary before addressing the clinical outcomes themselves. Further investigation is warranted to understand how SDOH affect screenings and outcomes in multiple disciplines of oncology and types of cancers as well as explore how SDOH affect the treatments sought by these vulnerable patients.
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

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.
The Relationships Between 25-Hydroxyvitamin D and Echocardiographic Parameters in Female Basketball Players
Authors: Radovanović Dragan , Stoičkov Viktor , Pechanova Olga , Scanlan Aaron T. , Jakovljević Vladimir , Stojanović Emilija
Published: May 2022

Objective:

This study was undertaken to (1) describe the cardiac structure and function and (2) to quantify the relationships between 25-hydroxyvitamin D [25(OH)D] and echocardiographic parameters in female basketball players.

Design:

A cross-sectional experimental design.

Setting:

Controlled laboratory setting.

Participants:

Professional, female basketball players (n = 18).

Intervention:

25(OH)D and echocardiographic screening at the midpoint of the in-season phase, over a 2-week period in late Fall.

Main Outcome Measures:

25(OH)D and echocardiographic parameters.

Results:

A high prevalence of vitamin D insufficiency was observed in the female players examined (77.8%), with most also displaying eccentric cardiac hypertrophy (77.8%). Nonsignificant, moderate correlations were found between 25(OH)D and structural echocardiographic parameters, including left atrium diameter (r = 0.34, P = 0.16), left ventricular (LV) end-systolic diameter (r = −0.46, P = 0.06), posterior wall thickness (r = 0.36, P = 0.14), LV mass (r = 0.30, P = 0.23), and LV index (r = 0.33, P = 0.18). Significant, large correlations were found between 25(OH)D and echocardiographic parameters indicative of systolic function, including LV ejection fraction (r = 0.59, P = 0.01), fractional shortening (r = 0.59, P = 0.01), and peak systolic mitral tissue velocity (r = 0.51, P = 0.003). Similarly, a significant, large correlation was found between 25(OH)D and diastolic function as indicated by mitral valve inflow deceleration time (r = 0.51, P = 0.03).

Conclusions:

Our findings suggest the importance of female basketball players maintaining 25(OH)D concentration, given its possible physiological benefits on cardiac structure and function.
Presenting Symptoms and Diagnosis of Vulvar Lichen Sclerosus in Premenopausal Women: A Cross-Sectional Study
Authors: Krapf Jill M. , Smith Alyssa B. , Cigna Sarah T. , Goldstein Andrew T.
Published: May 2022

Objectives/Purpose

Presenting symptoms of vulvar lichen sclerosus (LS) specific to premenopausal women are not well reported in the literature and may differ from those in postmenopausal women. This study aimed to characterize the presentation of vulvar LS among premenopausal women.

Materials and Methods

An observational web-based study was conducted in premenopausal women with biopsy-confirmed vulvar LS between the ages of 18–50 years. Participants completed a 28-question survey evaluating characteristics of symptoms, timing of diagnosis, alternate diagnoses, and presence of concomitant autoimmune conditions.

Results

Of the 956 responses received, 503 met inclusion criteria of biopsy-confirmed LS and premenopausal status. Average age of symptom onset was 27 years, and average age of diagnosis was 32 years, with a 4-year delay in diagnosis. Symptoms most present were dyspareunia (68%) and tearing with intercourse or vaginal insertion (63%). Symptoms that affect the individual most were also dyspareunia (44%) and tearing with intercourse or vaginal insertion (39%). Symptoms that most frequently prompted patients to seek medical attention were dyspareunia (35%), pruritus (31%) and tearing with intercourse or vaginal insertion (26%). Most common skin changes included hypopigmentation (81%), vulvar fissures (72%), and labial resorption (60%), with fissures affecting the individual the most (48%). Sixty-six percent of the respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (49%). Hypothyroidism was the most common concurrent autoimmune condition (10%).

Conclusions

Vulvar LS affects premenopausal women, commonly presenting with dyspareunia and tearing with intercourse. This condition should be considered and evaluated in premenopausal women presenting with vulvar symptoms and sexual pain.
Effects of Generic Exchange of Levodopa Medication in Patients With Parkinson Disease
Authors: Weitzel Johanna , Langer Klaus , Rose Olaf
Published: May 2022

Objectives

Generic exchange is common practice in most healthcare systems. This study investigated how patients with Parkinson disease (PD) perceived a switch of their levodopa medication and the resulting effects on their PD symptoms.

Methods

A questionnaire was developed, piloted, and finally distributed to 13,857 members of the national PD patient support group. It was designed to be completed by patients and their pharmacies. χ2 tests for independence statistics with or without Monte Carlo simulation were performed. Cramér φ and Cramér V were calculated. McNemar test was used to investigate whether a generic switch of a levodopa-containing medication had an impact on PD symptoms.

Results

Analyses were done with 410 finalized respondents of 13,857 distributed questionnaires. More than half of the responders were 75 years or older and rated themselves Hoehn and Yahr stages 3 to 5. Most patients were confused by a change of their medication. A total of 54.7% of the switchers (n = 148) reported swallowing difficulties with medication, which was significantly more frequent than with nonswitchers (37.3% of 204, P = 0.001). Adverse effects related to the switch were reported by 26.6% of all switchers (switchback rate, 20.5%). The patients at higher Hoehn and Yahr stages were affected to a greater extend.

Conclusions

Patients, who experienced any brand switch of their levodopa medication, frequently expressed distrust and confusion. Swallowing difficulties and negative effects on their symptoms were problems, which were more pronounced in advanced disease stages. It remains unclear whether the detrimental impact on therapy was caused by the brand switch or by a nocebo effect.
The Impact of a 22-Month Multistep Implementation Program on Speaking-Up Behavior in an Academic Anesthesia Department
Authors: Walther Fabio , Schick Carl , Schwappach David , Kornilov Evgeniya , Orbach-Zinger Sharon , Katz Daniel , Heesen Michael
Published: May 2022

Background

Speaking-up is a method of assertive communication that increases patient safety but often encounters barriers. Numerous studies describe programs introducing speaking-up with varying success; the common denominator seems to be the need for a multimodal and sustained approach to achieve the required change in behavior and culture for safer health care.

Methods

Before implementing a 22-month multistep program for establishing and strengthening speaking-up at our institution, we assessed perceived safety culture using the “Safety Attitudes Questionnaire.” After program completion, participants completed parts of the same Safety Attitudes Questionnaire relevant to speaking-up, and preresult and postresult were compared. In addition, levels of speaking-up and assertive communication were compared with a Swiss benchmark using results from the “Speaking-up About Patient Safety Questionnaire.”

Results

Safety Attitudes Questionnaire scores were significantly higher after program completion in 2 of 3 answered questions (median [first quartile, third quartile), 5.0 [4.0, 5.0] versus 4.0 [4.0, 5.0], P = 0.0002, and 5.0 [4.0, 5.0] versus 4.0 [4.0, 4.0] P = 0.002; n = 34). Our composite score on the Speaking-up About Patient Safety Questionnaire was significantly higher (mean ± SD, 5.9 ± 0.7 versus 5.2 ± 1.0;P < 0.001) than the benchmark (n = 65).

Conclusions

A long-term multimodal program for speaking-up was successfully implemented. Attitude and climate toward safety generally improved, and postprogram perceived levels of assertive communication and speaking-up were higher than the benchmark. These results support current opinion that multimodal programs and continued effort are required, but that speaking-up can indeed be strengthened.