bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual and institutional predisposing factors of MRSA surgical site infection and outcomes—a retrospective case-control-study in 14 European high-volume surgical centres
Authors: Rutz Jule , Naendrup Jan-Hendrik , Bruns Caroline , Classen Annika Y , Salmanton-García Jon , Seifert Harald , Sprute Rosanne , Stemler Jannik , Walker Sarah V , Cornely Oliver A , Liss Blasius J , Mellinghoff Sibylle C ,   SALT study group, Ankert Juliane , Bernard Louis , Bataille Camille , Couvé-Deacon Elodie , Ferrer María Fernández , Fortún Jesus , Galar Alicia , Guimard Thomas , Horcajada Juan P , Mollar Joan , Muñoz Patricia , Pletz Mathias W , Serracino-Inglott Ferdinand , Soriano Alex , Vilz Tim O
Published: April 2024

Objectives

To assess incidence rates of surgical site infections (SSI) by MRSA and to determine related factors and clinical outcome compared to MSSA, including country-specific, institutional and patient determinants.

Patients and methods

We performed a subgroup analysis of the Europe-wide SALT (NCT03353532) study population with MRSA SSI from 14 centres in France, Germany, Italy, Spain and the UK.

Results

An overall MRSA SSI incidence of 0.06% (n = 104) was found in 178 903 patients undergoing invasive surgery in 2016. Frequently observed comorbidities were chronic cardiovascular disease, diabetes and solid tumours. Compared to the overall MRSA SSI incidence, incidence rates were significantly higher in Spain (58 of 67 934 cases) and lower in Germany (16 of 46 443 cases; both P < 0.05). Centres with antibiotic stewardship (ABS) and infectious disease (ID) consultation programmes (n = 3/14) had lower MRSA rates (17 of 43 556 cases versus 61 of 83 048 cases, P < 0.05). In bivariate analyses, MRSA SSI patients were significantly older, had higher BMI and more comorbidities compared to MSSA (P < 0.05 each). Surgery performed between 6:00 and 12:00 pm led to higher MRSA proportions among S. aureus SSI (17 of 104 cases versus 62 of 640 cases, P < 0.05).

Conclusions

This study shows low overall and country-specific incidence rates of MRSA SSI in Europe. We could show significant differences between countries as well as between centres with established ABS and ID consultation programmes were observed. The number of those programmes seems too small against this background.
High prevalence of ceftriaxone-resistant and XDR Neisseria gonorrhoeae in several cities of Cambodia, 2022–23: WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP)
Authors: Ouk V , Heng L Say , Virak M , Deng S , Lahra M M , Frankson R , Kreisel K , McDonald R , Escher M , Unemo M , Wi T , Maatouk I ,   EGASP Cambodia Working Group, Penh Phnom , Fensham Vivian , Kersh Ellen , Cavailler Philippe , Mundade Yamuna , van Hal Sebastiaan J , Kundu Ratan L , Hogan Tiffany R , Whiley David M , Izumi Kiyohiko , Nishijima Takeshi
Published: April 2024

Objectives

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern. Ceftriaxone is the last effective and recommended option for empirical gonorrhoea therapy worldwide, but several ceftriaxone-resistant cases linked to Asia have been reported internationally. During January 2022–June 2023, the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) investigated N. gonorrhoeae AMR and epidemiological factors in patients from 10 clinical sentinel sites in Cambodia.

Methods

Urethral swabs from males with urethral discharge were cultured. ETEST determined the MIC of five antimicrobials, and EGASP MIC alert values and EUCAST breakpoints were used. EGASP demographic, behavioural and clinical variables were collected using a standardized questionnaire.

Results

From 437 male patients, 306 had positive N. gonorrhoeae cultures, AMR testing and complete epidemiological data. Resistance to ceftriaxone, cefixime, azithromycin and ciprofloxacin was 15.4%, 43.1%, 14.4% and 97.1%, respectively. Nineteen (6.2%) isolates were resistant to all four antimicrobials and, accordingly, categorized as XDR N. gonorrhoeae. These XDR isolates were collected from 7 of the 10 sentinel sites. No EGASP MIC alert values for gentamicin were reported. The nationally recommended cefixime 400 mg plus azithromycin 1 g (65.4%) or ceftriaxone 1 g plus azithromycin 1 g (34.6%) was used for treatment.

Conclusions

A high prevalence of ceftriaxone-resistant, MDR and XDR N. gonorrhoeae in several cities of Cambodia were found during 2022–23 in WHO EGASP. This necessitates expanded N. gonorrhoeae AMR surveillance, revision of the nationally recommended gonorrhoea treatment, mandatory test of cure, enhanced sexual contact notification, and ultimately novel antimicrobials for the treatment of gonorrhoea.
Measuring factors affecting honey bee (Hymenoptera: Apidae) attraction to soybeans using bioacoustics monitoring
Authors: Forrester Karlan C , Lin Chia-Hua , Johnson Reed M
Published: April 2024

Soybean (Glycine max (L.) Merr.) is an important agricultural crop around the world, and previous studies suggest that honey bees (Apis mellifera Linnaeus) can be a component for optimizing soybean production through pollination. Determining when bees are present in soybean fields is critical for assessing pollination activity and identifying periods when bees are absent so that bee-toxic pesticides may be applied. There are currently several methods for detecting pollinator activity, but these existing methods have substantial limitations, including the bias of pan trappings against large bees and the limited duration of observation possible using manual techniques. This study aimed to develop a new method for detecting honey bees in soybean fields using bioacoustics monitoring. Microphones were placed in soybean fields to record the audible wingbeats of foraging bees. Foraging activity was identified using the wingbeat frequency of honey bees (234 ± 14 Hz) through a combination of algorithmic and manual approaches. A total of 243 honey bees were detected over 10 days of recording in 4 soybean fields. Bee activity was significantly greater in blooming fields than in non-blooming fields. Temperature had no significant effect on bee activity, but bee activity differed significantly between soybean varieties, suggesting that soybean attractiveness to honey bees is heavily dependent on varietal characteristics. Refinement of bioacoustics methods, particularly through the incorporation of machine learning, could provide a practical tool for measuring the activity of honey bees and other flying insects in soybeans as well as other crops and ecosystems.
Soil macropores induced by plant root as a driver for vertical hydrological connectivity in Yellow River Delta
Authors: Xie Lumeng , Liu Jiakai , Li Yi , Huang Peisheng , Hipsey Matt , Zhang Mingxiang , Zhang Zhenming
Published: April 2024

The protection and management of the wetland should consider the changes in hydrological connectivity (HC) caused by the structural modifications of the soil macropores. The main purpose of our work is to clarify and quantify the influence of the soil macropores volume on the vertical soil hydrodynamic process mechanically and statistically by taking the form of a case study in Yellow River Delta (YRD), and further reveal the vertical hydrological connectivity in this area. Based on X-ray computed tomography and constant head permeability test, the results showed a highly spatial heterogeneity of the soil structure in the YRD, hydraulic parameter (Ks) was negatively correlated with bulk density and positively with soil macropore volume, soil aeration and maximum water capacity. Using Hydrus 1-D software and the Green–Ampt model, we estimated the characteristics of the hydrodynamic process in the soil without macropores, then evaluated the effect of the soil macropore on soil hydrodynamic process by comparing the experimental results with the simulation results. We found that increasing soil microporosity improved the convenience of water movement, which would enhance the HC of the region. The results will further help to reveal the eco-hydrological process at a vertical scale in soil and provide a theoretical guide for wetland conservation and restoration.
Observations of educational tourism utilizing dark tourism—emphasizing human interactions within recovering communities
Authors: McMichael William D Y
Published: April 2024

As Fukushima grapples with ongoing challenges related to reputational damage, it is becoming increasingly imperative to establish an effective means for global audiences to access, comprehend, and support the region's recovery efforts. To achieve this, Fukushima Prefecture has been strategically organizing educational tours tailored for international visitors, operating under the umbrella of ``Hope Tourism.'' These tours aim to bring about positive change by dispelling negative perceptions, offering a nuanced understanding of Fukushima's ongoing revitalization, and fostering connections between visitors and local residents. This study aims to contribute to the understanding of such tourism by providing an overview of Hope Tourism and addressing the reputational challenges faced by the prefecture. It will illustrate how experiences in Dark Tourism can effectively reshape a region's place identity, and serve as a proactive measure to alter perceptions of visitors to disaster-affected communities. Additionally, the study will analyze the learning outcomes of Hope Tourism experiences through the Fukushima Ambassadors Program, a short-term study abroad initiative provided by Fukushima University since 2012, which incorporates elements of Dark Tourism. Through these analyses, this study seeks to offer insights into the potential of educational tourism as a tool for fostering global support and understanding in the face of reputational challenges.
Tang Chang’an poetry automatic classification: a practical application of deep learning methods
Authors: Tian Mengmeng , Jia Qi , Wang Cong , Yang Juwang , Liu Xin
Published: April 2024

As the capital of Tang Dynasty, Chang’an was one of the most prosperous cities in the world at that time and had a profound influence on Tang poetry. Poets described Chang’an to illustrate the cultural features of the Tang Dynasty while also invoking emotions in readers. The study of Tang Chang’an poetry has important literary and historical value. In order to understand the interpretation and emotional expression of Tang Chang’an poetry more conveniently and clearly, we conducted a study using deep learning to classify Chang’an poetry into four classes: imperially assigned poetry (应制), emotional poetry (感怀), parting poetry (离别), and other poetry (其他). We suggested a comprehensive framework of text classification based on deep learning, including a text input module, feature encoder module, and classification module. We applied several mainstream deep neural network structures to extract features in different ways, which comprised convolutional neural network (CNN), Fasttext, bi-direction long-short-term memory network, and Attention mechanism. Based on our experimental findings, the CNN-based method achieved the best performance for the task. Our inference was that, in Chinese ancient poetry, the analysis of semantic content is more facilitated by local textual features rather than contextual features. We combined this inference with the theory of image in Chinese ancient poetry to analyze the suitability of the deep learning techniques for the study of Chinese ancient poetry.
Switch to Web-Based Surveys During COVID-19 Pandemic Left Out the Most Religious, Creating a False Impression of Rapid Religious Decline
Authors: Schnabel Landon , Bock Sean , Hout Michael
Published: April 2024

Religion appears to have taken a nosedive during the pandemic, including previously persistent forms of intense religion such as strong affiliation and biblical literalism. However, this apparent secularization is the result of mode effects. The gold standard General Social Survey (GSS) switched to online rather than face-to-face interviews and the response rate plunged to 17%. Parallel analyses of GSS panel data demonstrate that this mode switch introduced substantial nonresponse bias. Illustratively, biblical literalism was almost 50% higher among those who declined to participate (36%) than those who participated in the online survey (25%). Rather than declining, intense religion persisted if not rose over time among those willing to participate in a push-to-web survey. The apparent decline was simply a result of disillusioned, distrusting, disinformed, disadvantaged, and disconnected people being much less likely to agree to participate. Intense religion and other social phenomena are underrepresented and thereby underestimated in online surveys with substantial nonresponse, including those using population sampling methods. The trend in survey research toward these types of surveys could be expected to give a false impression of secularization and other social change going forward—including making society look less disillusioned, distrusting, disinformed, disadvantaged, and disconnected than it is.
hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1‐mediated THBS1 transcription
Authors: Ma Xiao , Xu Lei , Gong Shuai , Wu Nai , Guo Jiaxuan , Feng Xinyu , Zhao Mengmeng , Qiu Sancheng , Sun Ming , Zhang Chong , Zhang Xiuzhong , Ren Zeqiang , Zhang Pengbo
Published: April 2024

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second‐generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT‐PCR and Kaplan–Meier survival curves. Gain‐ and loss‐of‐function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.
Lingering effects of COVID-19 in the care of perioperative patients
Authors: Jia Linjia , Navare Sagar , Hoyler Marguerite
Published: April 2024

Purpose of review

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can lead to organ dysfunction and clinical symptoms beyond the acute infection phase. These effects may have significant implications for the management of perioperative patients. The purpose of this article is to provide a systems-based approach to the subacute and chronic effects of SARS-CoV-2 that are most relevant to anesthesiology practice.

Recent findings

In 2024, COVID-19 remains a concern for anesthesiologists due ongoing new infections, evolving viral strains, and relatively low rates of booster vaccination in the general population. A growing body of literature describes the post-COVID-19 syndrome in which patients experience symptoms more than 12 weeks after acute infection. Recent literature describes the lingering effects of SARS-CoV-2 infection on all major organ systems, including neurologic, pulmonary, cardiovascular, renal, hematologic, and musculoskeletal, and suggests an increased perioperative mortality risk in some populations.

This review offers anesthesiologists an organ system-based approach to patients with a history of COVID-19. Recognizing the long-term sequelae of SARS-CoV-2 infection can help anesthesiologists to better evaluate perioperative risk, anticipate clinical challenges, and thereby optimize patient care.
Implementation of an Extubation Readiness Guideline for Preterm Infants
Authors: Cobb Emily B. , Fitzgerald Jennifer , Stadd Karen , Gontasz Michelle , Wise Barbara
Published: April 2024

Background:

Intubated preterm infants 326/7 weeks or less of gestation in a mid-Atlantic level IV neonatal intensive care unit (NICU) faced a high number of ventilator days. Based on 6 weeks of electronic health record (EHR) chart audits of extubations in this NICU in 2021, 44% of preterm infants 326/7 weeks or less of gestation were intubated for more than 28 days, with an average of 23 days on a ventilator. This NICU lacked a standardized extubation guideline providing criteria to drive extubation eligibility.

Purpose:

The purpose of this quality improvement (QI) project was to implement and evaluate the effectiveness of an extubation readiness guideline in preterm infants 326/7 weeks or less of gestation in a mid-Atlantic level IV NICU.

Methods:

This project occurred over a 17-week period in 2021. Implementation included a multidisciplinary committee formation, identification of champions, NICU staff education, completion of a guideline checklist by bedside nursing (for eligible patients), clinician reminders, and chart audits for collection of pre-/postimplementation data. Staff education completion, guideline use and compliance, demographic patient data, ventilator days, time to first extubation, and need for reintubation were tracked.

Results:

Postimplementation data indicated decreased need for intubation for more than 28 days, ventilator days, and days to first extubation attempt.

Implications for Practice and Research:

Results suggested that implementation of the evidence-based guideline was effective in decreasing average total ventilator days for preterm infants 326/7 weeks or less of gestation.
Central Retinal Vein Occlusion in COVID-19
Authors: Saha Arunava , Abraham George
Published: April 2024

Central retinal vein occlusion (CRVO) secondary to severe acute respiratory syndrome coronavirus 2–induced coagulation abnormalities is rare. A 32-year-old man presented with bilateral CRVO. He had a history of retinal migraine with occasional floaters and received 2 primary and a booster dose of the BNT162b2 vaccine 7 months prior. Four months before presentation, he developed acute blurring of vision in the left eye and was diagnosed with a nonischemic CRVO with dot-blot hemorrhages. He was managed conservatively with aspirin. Three weeks later, he contracted COVID-19 and received 5 days of nirmatrelvir/ritonavir. Four weeks after his COVID infection, repeat fundoscopic evaluation demonstrated resolving hemorrhages in the left eye but a new CRVO in the right eye. Antivascular endothelial growth factor injections were deferred because of normal visual acuity. He had a normal magnetic resonance imaging of the brain and a normal bilateral carotid duplex and was planned for close follow-up with ophthalmology. COVID-19 patients presenting with visual symptoms should be screened for CRVO.
Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study
Authors: Mekkan-Bouv Hez M. , Derbey L. , de Mestier L. , Lorenzo D. , Walter T. , Perrier M. , Cadiot G. , Goichot B. , Pracht M. , Lièvre A , Coriat R. , Valancot S. , Guimbaud R. , Carrere N. , Bacoeur-Ouzillou O. , Belleannée G. , Smith Denis , Laboureau S. , Hescot Sophie , Julie Catherine , Teissier M.P. , Thereaux J. , Ferru A. , Evrard C. , Mathonnet M. , Christou N.
Published: April 2024

Introduction:

Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors’ study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival.

Methods:

A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group.

Results:

A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P<0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous (P=0.001). In the sub-group analysis of G1–G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P=0.977) and location (P=0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P=0.387).

Conclusion:

Regardless of the resection type (ER or SR) of G1–G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.
Perioperative textbook outcomes of minimally invasive pancreatoduodenectomy: a multicenter retrospective cohort analysis in a Korean minimally invasive pancreatic surgery registry
Authors: Kwon Jaewoo , Kang Chang Moo , Jang Jin-Young , Yoon Yoo-Seok , Kwon Hyung Jun , Choi In Seok , Kim Hee Joon , Shin Sang Hyun , Kang Sang Hyun , Moon Hyung Hwan , Hwang Dae Wook , Kim Song Cheol ,   for the Korean Study Group on Minimally Invasive Pancreatic Surgery (K-MIPS)
Published: April 2024

Background:

The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD).

Materials and methods:

The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD.

Results:

Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien–Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P<0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P=0.001), lower 90-day mortality (0.5% vs. 2.7%, P=0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P=0.006) than those low-volume centers.

Conclusion:

MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease.
The Value of Traditional Medicine Should not be Underestimated—Traditional Chinese Medicine in Treatment of Autoimmune Diseases
Authors: Novikov Yurii O , Akopyan Anait P
Published: April 2024

Autoimmune diseases of the nervous system (ADNS) are characterized by the formation of a pronounced neurologic deficit and often lead to disability. The attention of doctors and researchers is increasingly attracted by complementary medicine as adjuvant or preventive therapy for various diseases, including autoimmune diseases. Traditional Chinese medicine (TCM) is a combination of treatment methods that include acupuncture, herbal medicine, dietetics, physical exercises, and other methods that are often used in conjunction with recognized approaches of official medical science. The article describes the application of TCM techniques in autoimmune diseases of the nervous system, and demonstrates clinical experience in the use of acupuncture, herbal medicine, diets and physical exercises. Traditional and complementary medicine is an important and often underestimated healthcare resource, especially in the prevention and treatment of autoimmune diseases of the nervous system.
Prepandemic Resilience to Trauma and COVID-19 Infection in Older Women
Authors: Scoglio Arielle A.J. , Choi Karmel W. , Nishimi Kristen , Sampson Laura , Koenen Karestan C. , Roberts Andrea L. , Jha Shaili , Kubzansky Laura D.
Published: April 2024

Objective

Prior work suggests that psychological resilience to trauma may protect not only mental but also physical health. This study examined the relationship of prepandemic psychological resilience to lifetime trauma with self-reported COVID-19 infection and symptoms during the early years of the COVID-19 pandemic.

Methods

Data are from 18,670 longitudinal cohort participants in the Nurses’ Health Study II. Based on prior evidence that trauma and subsequent distress can increase infection risk and severity, and that psychological assets may offset this risk, we hypothesized higher versus lower psychological resilience to prior trauma would be associated with lower risk for COVID-19 infection. Prepandemic resilience was assessed via self-report between 2017 and 2019 based on self-reported lifetime trauma exposure and psychological health. COVID-19 infection and symptoms were self-reported on seven questionnaires administered between May 2020 and October 2021, from which we derived a composite outcome measure of probable COVID-19 infection, defined as having 3+ COVID-19 symptoms (out of 9) and/or a positive COVID-19 test result at any single assessment.

Results

Multivariable regression revealed significant associations between higher prepandemic resilience scores and lower risk for probable COVID-19 infection, adjusting for sociodemographic and COVID-19–related risk factors (risk ratio [RR] = 0.90 [95% confidence interval {CI}, 0.87–0.93]). Considering subcomponents of the composite COVID-19 infection measure separately, prepandemic resilience was significantly associated with lower risk of reported symptoms (RR = 0.83 [95% CI, 0.79–0.88]), but not with a positive test result alone (RR = 0.96 [95% CI, 0.91–1.01]).

Conclusion

Identifying protective factors for infection risk may help inform psychosocial interventions to improve health outcomes.
Individualized dynamic risk assessment for multiple myeloma
Authors: Murie Carl , Turkarslan Serdar , Patel Anoop , Coffey David G. , Becker Pamela S. , Baliga Nitin S.
Published: April 2024

Background

Individualized treatment decisions for patients with multiple myeloma (MM) requires accurate risk stratification that takes into account patient-specific consequences of genetic abnormalities and tumor microenvironment on disease outcome and therapy responsiveness.

Methods

Previously, SYstems Genetic Network AnaLysis (SYGNAL) of multi-omics tumor profiles from 881 MM patients generated the mmSYGNAL network, which uncovered different causal and mechanistic drivers of genetic programs associated with disease progression across MM subtypes. Here, we have trained a machine learning (ML) algorithm on activities of mmSYGNAL programs within individual patient tumor samples to develop a risk classification scheme for MM that significantly outperformed cytogenetics, International Staging System, and multi-gene biomarker panels in predicting risk of PFS across four independent patient cohorts.

Results

We demonstrate that, unlike other tests, mmSYGNAL can accurately predict disease progression risk at primary diagnosis, pre- and post-transplant and even after multiple relapses, making it useful for individualized dynamic risk assessment throughout the disease trajectory.

Conclusion

mmSYGNAL provides improved individualized risk stratification that accounts for a patient’s distinct set of genetic abnormalities and can monitor risk longitudinally as each patient’s disease characteristics change.
Concordance of whole-genome long-read sequencing with standard clinical testing for Prader-Willi and Angelman syndromes
Authors: Paschal Cate R. , Zalusky Miranda P. G. , Beck Anita E. , Gillentine Madelyn A. , Narayanan Jaya , Damaraju Nikhita , Goffena Joy , Storz Sophie H. R. , Miller Danny E.
Published: April 2024

Current clinical testing approaches for individuals with suspected imprinting disorders are complex, often requiring multiple tests performed in a stepwise fashion to make a precise molecular diagnosis. We investigated whether whole-genome long-read sequencing (LRS) could be used as a single data source to simultaneously evaluate copy number variants (CNVs), single nucleotide variants (SNVs), structural variants (SVs), and differences in methylation in a cohort of individuals known to have either Prader-Willi or Angelman syndrome. We evaluated 25 individuals sequenced to an average depth of coverage of 36x on an Oxford Nanopore PromethION. A custom one-page report was generated that could be used to assess copy number, SNVs, and methylation patterns at select CpG sites within the 15q11.2-q13.1 region and prioritize candidate pathogenic variants inUBE3A. After training with three positive controls, three analysts blinded to the known clinical diagnosis arrived at the correct molecular diagnosis for 22 out of 22 cases (20 true positive, 2 negative controls). Our findings demonstrate the utility of LRS as a single, comprehensive data source for complex clinical testing, offering potential benefits such as reduced testing costs, increased diagnostic yield, and shorter turnaround times in the clinical laboratory.
Three-dimensional multi-target super-resolution microscopy of cells using Metal-Induced Energy Transfer and DNA-PAINT
Authors: Oleksiievets Nazar , Mougios Nikolaos , Jans Daniel C. , Hauke Lara , Thiele Jan Christoph , Basak Samrat , Jakobs Stefan , Opazo Felipe , Enderlein Jörg , Tsukanov Roman
Published: April 2024

DNA-points accumulation for imaging in nanoscale topography (DNA-PAINT) is a potent variant of single-molecule localization microscopy (SMLM) which is highly effective for multiplexed super-resolution imaging. It achieves localization precision down to nanometers in the lateral direction. However, its routine axial localization precision is approximately three-fold lower as compared to the lateral localization precision. Recently, a technique known as Metal-Induced Energy Transfer (MIET) has been introduced, offering excellent axial resolution at the nanometer scale up to 200 nm above a surface. MIET is characterized by a low entry barrier, as its sole technical requirement is the availability of a fluorescence lifetime imaging modality. In this study, we harness the synergy between the exceptional axial resolution provided by MIET and the lateral resolution achieved with DNA-PAINT (MIET-PAINT) to accomplish multitarget 3D super-resolution imaging. We implemented MIET-PAINT using a wide-field fluorescence lifetime imaging microscope. We validated our technique by measuring the height of emitters placed on top of spacers of known thicknesses. We then demonstrated multiplexed MIET-PAINT imaging of fixed cells to visualize mechanotransduction proteins in the focal adhesion complex (FAC) and the cytoskeleton. We explored the structural arrangement of paxillin, zyxin, and actin stress fibers in U2OS cells and discovered that MIET-PAINT can reliably address multiple targets, providing lateral and axial nanometerscale resolution.
Advancing knowledge of West African morning glories: a taxonomic revision ofIpomoeaL. (Convolvulaceae) from Ghana
Authors: Williams Benjamin Darko , Francisco Ruth Cristóvão , Mewded Befkadu , Oppong Christiana Peprah , Bosomtwi-Ayensu Claudia , Masinde Collins Wafula , Chukwuma Deborah Moradeke , Gadisa Deresa Abetu , Yeboah Doreen Donkor , Ahossou Enangnon Oscar Doré , Rasaminirina Fitiavana , Precious Igho-Osagie Uhunwa , Korir Mercy Jebiwott , Antwi-Boasiako Kwasi Boateng , Mfodwo Raymond Attah , Musa Mutegeki Alislam Said , Atta-Adjei Peter , Akomatey Peter Kwasi , Kumordzie Seyiram , Borosova Renata , Tang Cheung , Asase Alex , Ameka Gabriel , Simões Ana Rita Giraldes
Published: April 2024

Ghana’s plant diversity is estimated at 2,974 plant species, belonging to 1,077 genera and 173 plant families. However, a Flora of Ghana is yet inexistent: targeted floristic and taxonomic studies are still much needed to document the plant diversity of the country fully at the family, generic and species levels. This is essential for identifying priority conservation areas in the country and support further research in crop wild relatives or medicinal plants, which will help tackle food insecurity and improve livelihoods. In this study, we provide a taxonomic revision of theIpomoea spp.in Ghana to enhance their identification, conservation and sustainable utilization as food and medicine among other uses. An extensive literature review was carried out, including historical references and online taxonomic databases, to recover information on accepted names, type specimens and synonyms, followed by consultation of herbarium specimens at GC herbaria, to retrieve morphological information and database specimens. Specimen locality information was georeferenced, and records plotted onto distribution maps. As a result, this work provides an identification key to the species ofIpomoeaof Ghana, nomenclatural information, comprehensive morphological descriptions, detailed list of examined specimens, distribution maps and notes on conservation status and traditional plant uses. In total, 28 species are fully described, 20 of which are native and eight introduced from the Americas; five are new records to Ghana.
Evaluating Large Language Models for Drafting Emergency Department Discharge Summaries
Authors: Williams Christopher Y.K. , Bains Jaskaran , Tang Tianyu , Patel Kishan , Lucas Alexa N. , Chen Fiona , Miao Brenda Y. , Butte Atul J. , Kornblith Aaron E.
Published: April 2024

Importance

Large language models (LLMs) possess a range of capabilities which may be applied to the clinical domain, including text summarization. As ambient artificial intelligence scribes and other LLM-based tools begin to be deployed within healthcare settings, rigorous evaluations of the accuracy of these technologies are urgently needed.

Objective

To investigate the performance of GPT-4 and GPT-3.5-turbo in generating Emergency Department (ED) discharge summaries and evaluate the prevalence and type of errors across each section of the discharge summary.

Design

Cross-sectional study.

Setting

University of California, San Francisco ED.

Participants

We identified all adult ED visits from 2012 to 2023 with an ED clinician note. We randomly selected a sample of 100 ED visits for GPT-summarization.

Exposure

We investigate the potential of two state-of-the-art LLMs, GPT-4 and GPT-3.5-turbo, to summarize the full ED clinician note into a discharge summary.

Main Outcomes and Measures

GPT-3.5-turbo and GPT-4-generated discharge summaries were evaluated by two independent Emergency Medicine physician reviewers across three evaluation criteria: 1) Inaccuracy of GPT-summarized information; 2) Hallucination of information; 3) Omission of relevant clinical information. On identifying each error, reviewers were additionally asked to provide a brief explanation for their reasoning, which was manually classified into subgroups of errors.

Results

From 202,059 eligible ED visits, we randomly sampled 100 for GPT-generated summarization and then expert-driven evaluation. In total, 33% of summaries generated by GPT-4 and 10% of those generated by GPT-3.5-turbo were entirely error-free across all evaluated domains. Summaries generated by GPT-4 were mostly accurate, with inaccuracies found in only 10% of cases, however, 42% of the summaries exhibited hallucinations and 47% omitted clinically relevant information. Inaccuracies and hallucinations were most commonly found in the Plan sections of GPT-generated summaries, while clinical omissions were concentrated in text describing patients’ Physical Examination findings or History of Presenting Complaint.

Conclusions and Relevance

In this cross-sectional study of 100 ED encounters, we found that LLMs could generate accurate discharge summaries, but were liable to hallucination and omission of clinically relevant information. A comprehensive understanding of the location and type of errors found in GPT-generated clinical text is important to facilitate clinician review of such content and prevent patient harm.
Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity
Authors: Heng Teng Hiang , Walter Klaudia , Huang Qin Qin , Karjalainen Juha , Daly Mark J , Heyne Henrike O. ,   FinnGen, Malawsky Daniel , Kalantzis Georgios ,   Genes and Health Research Team, van Heel David A , Martin Hilary C
Published: April 2024

Genetic association studies have focused on testing additive models in cohorts with European ancestry. Little is known about recessive effects on common diseases, specifically for non-European ancestry. Genes & Health is a cohort of British Pakistani and Bangladeshi individuals with elevated rates of consanguinity and endogamy, making it suitable to study recessive effects. We imputed variants into 44,190 genotyped individuals, using two imputation panels: a set of 4,982 whole-exome-sequences from within the cohort, and the TOPMed-r2 panel. We performed association testing with 898 diseases from electronic health records. We identified 185 independent loci that reached standard genome-wide significance (p<5x10-8) under the recessive model and had p-values more significant than under the additive model. 140 loci demonstrated nominally-significant (p<0.05) dominance deviation p-values, confirming a recessive association pattern. Sixteen loci in three clusters were significant at a Bonferroni threshold accounting for multiple phenotypes tested (p<5.5x10-12). In FinnGen, we replicated 44% of the expected number of Bonferroni-significant loci we were powered to replicate, at least one from each cluster, including an intronic variant in PNPLA3 (rs66812091) and non-alcoholic fatty liver disease, a previously reported additive association. We present novel evidence suggesting that the association is recessive instead (OR=1.3, recessive p=2x10-12, additive p=2x10-11, dominance deviation p=3x10-2, FinnGen recessive OR=1.3 and p=6x10-12). We identified a novel protective recessive association between a missense variant in SGLT4 (rs61746559), a sodium-glucose transporter with a possible role in the renin-angiotensin-aldosterone system, and hypertension (OR=0.2, p=3x10-8, dominance deviation p=7x10-6). These results motivate interrogating recessive effects on common diseases more widely.
Multi-SpinX: An Advanced Framework for Automated Tracking of Mitotic Spindles and Kinetochores in Multicellular Environments
Authors: Chai Binghao , Efstathiou Christoforos , Choudhury Muntaqa S. , Kuniyasu Kinue , Jain Saakshi Sanjay , Maharea Alexia-Cristina , Tanaka Kozo , Draviam Viji M.
Published: April 2024

SpinX, an AI-guided spindle tracking software, allows the 3-dimensional (3D) tracking of metaphase spindle movements in mammalian cells. Using over 900 images of dividing cells, we create the Multi-SpinX framework to significantly expand SpinX’s applications: a) to track spindles and cell cortex in multicellular environments, b) to combine two object tracking (spindle with kinetochores marked by centromeric probes) and c) to extend spindle tracking beyond metaphase to prometaphase and anaphase stages where spindle morphology is different. We have used a human-in-the-loop approach to assess our optimisation steps, to manually identify challenges and to build a robust computational pipeline for segmenting kinetochore pairs and spindles. Spindles of both H1299 and RPE1 cells have been assessed and validated for use through Multi-SpinX, and we expect the tool to be versatile in enabling quantitative studies of mitotic subcellular dynamics.
Causal role of frontocentral beta oscillation in comprehending linguistic communicative functions
Authors: Chang Wenshuo , Zhao Xiaoxi , Wang Lihui , Zhou Xiaolin
Published: April 2024

Linguistic communication is often considered as an action serving the function of conveying the speaker’s goal to the addressee. Although neuroimaging studies have suggested a role of the motor system in comprehending communicative functions, the underlying mechanism is yet to be specified. Here, by 2 EEG experiments and a tACS experiment, we demonstrate that the frontocentral beta oscillation, which represents action states, plays a crucial part in linguistic communication understanding. Participants read scripts involving 2 interlocutors and rated the interlocutors’ attitudes. Each script included a critical sentence said by the speaker expressing a context-dependent function of either promise, request, or reply to the addressee’s query. These functions were behaviorally discriminated, with higher addressee’s will rating for the promise than for the reply and higher speaker’s will rating for the request than for the reply. EEG multivariate analyses showed that different communicative functions were represented by different patterns of frontocentral beta activity but not by patterns of alpha activity. Further tACS results showed that, relative to alpha tACS and sham stimulation, beta tACS improved the predictability of communicative functions of request or reply, as measured by the speaker’s will rating. These results convergently suggest a causal role of the frontocentral beta activities in comprehending linguistic communications.

Highlights

The frontocentral beta activity patterns discriminate communicative functions.

The frontocentral beta activity plays a causal role in comprehending the functions.

The comprehension could be subserved by the mental simulation of the communication.

Our findings connect the idea of embedded semantics with the speech act theory.
Elucidating role of long non-coding RNAs ofTamarindus indicaLinn. in post-transcriptional gene regulation
Authors: Roy Chowdhury Moumita , Kumar Aman , Besra Alfred , Basak Jolly
Published: April 2024

Tamarindus indica, commonly known as tamarind, is a rich source of carbohydrates, proteins, lipids, fatty acids, vitamins, minerals and different bioactive compounds. It is well established that long non-coding RNAs (lncRNAs) play important role in transcriptional, post-transcriptional and epigenetic regulation. In spite of the tamarind genome information available, handful of studies have been done on its non-coding genome. In this study, 320 tamarind lncRNAs have been predicted by computational methods. Along with the experimental validation of seven randomly chosen lncRNAs, functional analysis of the predicted lncRNAs along with their targets elucidated their roles in various biological pathways. Sequence analysis of these predicted lncRNAs reveals the presence of different motifs and TRs. Our analysis provides information about the non-coding genome of tamarind and their involvement in gene regulation, which may be used to gain more knowledge about the medicinal properties of tamarind.
Similar, but not the same: multi-omics comparison of human valve interstitial cells and osteoblast osteogenic differentiation expanded with an estimation of data-dependent and data-independent PASEF
Authors: Lobov Arseniy , Kuchur Polina , Boyarskaya Nadezhda , Perepletchikova Daria , Taraskin Ivan , Ivashkin Andrei , Kostina Daria , Khvorova Irina , Uspensky Vladimir , Repkin Egor , Denisov Evgeny , Gerashchenko Tatiana , Tikhilov Rashid , Bozhkova Svetlana , Karelkin Vitaly , Wang Chunli , Xu Kang , Malashicheva Anna
Published: April 2024

Osteogenic differentiation is crucial in normal bone formation and pathological calcification, such as calcific aortic valve disease (CAVD). Understanding the proteomic and transcriptomic landscapes underlying this differentiation can unveil potential therapeutic targets for CAVD. In this study, we employed the timsTOF Pro platform to explore the proteomic profiles of valve interstitial cells (VICs) and osteoblasts during osteogenic differentiation, utilizing three data acquisition/analysis techniques: Data-Dependent Acquisition (DDA-PASEF) and Data-Independent Acquisition (DIA-PASEF) with a classic library based and machine learning-based “library-free” search (DIA-ML). RNA-seq complemented comparative proteome coverage analysis to provide a comprehensive biological reference. We reveal distinct proteomic and transcriptomic profiles between VICs and osteoblasts, highlighting specific biological processes in their osteogenic differentiation pathways. Furthermore, the study identified potential therapeutic targets for CAVD, including the differential expression of proteins such as MAOA and ERK1/2 pathway in VICs. From a technical perspective, the DIA-ML offers significant advantages and seems the method of choice for routine proteomics.