bluuebunny/crossref_metadata_2025 huggingface dataset:
Home or hospital? An observational study of what affects the place of death of people with COVID-19 in Mexico
Authors: Núñez Isaac
Published: April 2023

Background

Out-of-hospital deaths increased during peak coronavirus disease 2019 (COVID-19) pandemic periods. However, aside from COVID-19 severity, which variables are related to being hospitalized have not been properly studied. We examine the association of several variables with dying at home from COVID-19 as opposed to in a hospital.

Methods

We used COVID-19 open data from Mexico City from March 2020 until February 2021. A causal model was prespecified to identify variables of interest. Adjusted logistic regressions were performed to calculate ORs for associations between variables of interest and dying out of hospital due to COVID-19.

Results

Among 61 112 people who died due to COVID-19, 8080 died out of hospital. Older age (OR 3.49, age 90 vs 60 y), male sex (OR 1.18) and higher bed occupancy (OR 2.68, 90% vs 50% occupancy) were positively associated with dying outside of hospital.

Conclusion

Older age could confer different patient wishes or less ability to look for healthcare. Higher bed occupancy may have prevented hospital admission from people who required in-hospital care.
Discovery of the Hrp Type III Secretion System in Phytopathogenic Bacteria: How Investigation of Hypersensitive Cell Death in Plants Led to a Novel Protein Injector System and a World of Inter-Organismal Molecular Interactions Within Plant Cells
Authors: Kvitko Brian H. , Collmer Alan
Published: April 2023

In the early 1960s, Pseudomonas syringae and other host-specific phytopathogenic proteobacteria were discovered to elicit a rapid, resistance-associated death when infiltrated at high inoculum levels into nonhost tobacco leaves. This hypersensitive reaction (or response; HR) was a useful indicator of basic pathogenic ability. Research over the next 20 years failed to identify an elicitor of the HR but revealed that its elicitation required contact between metabolically active bacterial and plant cells. Beginning in the early 1980s, molecular genetic tools were applied to the HR puzzle, revealing the presence in P. syringae of clusters of hrp genes, so named because they are required for the HR and pathogenicity, and of avr genes, so named because their presence confers HR-associated avirulence in resistant cultivars of a host plant species. A series of breakthroughs over the next two decades revealed that (i) hrp gene clusters encode a type III secretion system (T3SS), which injects Avr (now “effector”) proteins into plant cells, where their recognition triggers the HR; (ii) T3SSs, which are typically present in pathogenicity islands acquired by horizontal gene transfers, are found in many bacterial pathogens of plants and animals and inject many effector proteins, which are collectively essential for pathogenicity; and (iii) a primary function of phytopathogen effectors is to subvert non-HR defenses resulting from recognition of conserved microbial features presented outside of plant cells. In the 2000s, Hrp system research shifted to extracellular components enabling effector delivery across plant cell walls and plasma membranes, regulation, and tools for studying effectors.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Residency Program Directors’ Views on Research Conducted During Medical School: A National Survey
Authors: Wolfson Rachel K. , Fairchild Paige C. , Bahner Ingrid , Baxa Dwayne M. , Birnbaum Deborah R. , Chaudhry Sarwat I. , Chretien Katherine C. , DeFranco Donald B. , Deptola Amber Z. , LaConte Leslie E.W. , Lin Jenny J. , Petch Lee Leslie , Powers Maureen A. , Ropson Ira J. , Sankaran Saumya M. , Sawarynski Kara E. , Sozio Stephen M.
Published: April 2023

Purpose

With the United States Medical Licensing Examination Step 1 transition to pass/fail in 2022, uncertainty exists regarding how other residency application components, including research conducted during medical school, will inform interview and ranking decisions. The authors explore program director (PD) views on medical student research, the importance of disseminating that work, and the translatable skill set of research participation.

Method

Surveys were distributed to all U.S. residency PDs and remained open from August to November 2021 to query the importance of research participation in assessing applicants, whether certain types of research were more valued, productivity measures that reflect meaningful research participation, and traits for which research serves as a proxy. The survey also queried whether research would be more important without a numeric Step 1 score and the importance of research vs other application components.

Results

A total of 885 responses from 393 institutions were received. Ten PDs indicated that research is not considered when reviewing applicants, leaving 875 responses for analysis. Among 873 PDs (2 nonrespondents), 358 (41.0%) replied that meaningful research participation will be more important in offering interviews. A total of 164 of 304 most competitive specialties (53.9%) reported increased research importance compared with 99 of 282 competitive (35.1%) and 95 of 287 least competitive (33.1%) specialties. PDs reported that meaningful research participation demonstrated intellectual curiosity (545 [62.3%]), critical and analytical thinking skills (482 [55.1%]), and self-directed learning skills (455 [52.0%]). PDs from the most competitive specialties were significantly more likely to indicate that they value basic science research vs PDs from the least competitive specialties.

Conclusions

This study demonstrates how PDs value research in their review of applicants, what they perceive research represents in an applicant, and how these views are shifting as the Step 1 exam transitions to pass/fail.
Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren's syndrome
Authors: Li Mucong , Li Mengtao , Qiao Lin , Wu Chanyuan , Xu Dong , Zhao Yan , Zeng Xiaofeng
Published: April 2023

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with high prevalence and possible poor prognosis. Though the pathogenesis of pSS has not been fully elucidated, B cell hyperactivity is considered as one of the fundamental abnormalities in pSS patients. It has long been identified that Janus kinases-signal transducer and activator of transcription (JAK-STAT) signaling pathway contributes to rheumatoid arthritis and systemic lupus erythematosus. Recently, increasing numbers of studies have provided evidence that JAK-STAT pathway also has an important role in the pathogenesis of pSS via direct or indirect activation of B cells. Signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5 activated by various cytokines and ribonucleic acid contribute to pSS development, respectively or synergically. These results reveal the potential application of Janus kinase inhibitors for treatment of pSS, which may fundamentally improve the quality of life and prognosis of patients with pSS.
Aesthetic Outcomes of the Adipofascial Turnover Flap for Nasal Defects
Authors: Canzoneri Christina N. , Capito Anthony E.
Published: April 2023

Background:

The single-stage adipofascial turnover (AFT) flap with full-thickness skin grafting is a novel technique that has been demonstrated as a safe, reliable, and cost-effective alternative to forehead flaps for nasal tip reconstruction. The purpose of this study was to compare aesthetic outcomes of these reconstructive techniques.

Methods:

A retrospective review was conducted of patients who underwent either a forehead flap or an AFT flap for nasal reconstruction between January 2016 and January 2021. Aesthetic outcomes were compared via patient surveys and photographic analysis by plastic surgeons. All photographs were standardized and masked to conceal which reconstructive technique was utilized. Wilcoxon rank-sum tests and t-tests were performed to determine significance.

Results:

Ten forehead flaps and 22 AFT flaps were performed between January 2016 and January 2021. Seven forehead flap patients and 18 AFT flap patients participated in the aesthetic outcome survey. Seven forehead flap postoperative photographs and 20 AFT flap postoperative photographs were available for analysis. Patients who underwent forehead flap reconstruction reported higher satisfaction for color match of the reconstruction to the surrounding nasal skin (P = 0.005). Otherwise, there was no statistical significance between the two patient groups. There was no statistical difference in the photographic analysis of the two groups.

Conclusion:

The single-stage AFT flap with full thickness skin grafting provides similar aesthetic outcomes compared with the two-stage forehead flap when reconstructing large defects of the nasal tip, which is supported by both patient-reported outcome measures and standardized photographic analysis by a panel of plastic surgeons.
Risk Factors of Progression in Low-tumor Burden Follicular Lymphoma Initially Managed by Watch and Wait in the Era of PET and Rituximab
Authors: Rodier Cyrielle , Kanagaratnam Lukshe , Morland David , Herbin Adélie , Durand Amandine , Chauchet Adrien , Choquet Sylvain , Colin Philippe , Casasnovas René Olivier , Deconinck Eric , Godard François , Delmer Alain , Rossi Cédric , Durot Eric
Published: April 2023

Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1–3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed tomography (PET-CT), total metabolic tumor volume (TMTV) ≥14 cm3 and standardized Dmax (reflecting tumor dissemination) >0.32 m−1 were also associated with shorter TLT (HR = 3.4; P = 0.004 and HR = 2.4; P = 0.007, respectively). In multivariate models combining PET-CT parameters and clinical variables, TMTV remained independent predictor of shorter TLT. These simple parameters could help to identify FL patients initially observed at higher risk of early progression. The role of PET-CT (extranodal sites and PET metrics) in low-burden FL appears promising and warrants further assessment in large cohorts.
Optic Disc Measurements in Children by Optical Coherence Tomography
Authors: Hashemi Hassan , Khabazkhoob Mehdi , Heydarian Samira , Emamian Mohammad Hassan , Fotouhi Akbar
Published: April 2023

Précis:

This study showed the distribution of optic disc indices in a population-based sample of Iranian children in detail. Refractive errors and biometric components are among the ocular factors that are related to these indices.

Purpose:

To determine the normative value of optic nerve indices in children and their association with ocular and demographic factors.

Methods:

A cross-sectional study was conducted in 2018. Biometry was done using the Allegro Biograph, and macular indices were measured by OCT imaging.

Results:

After applying the exclusion criteria, 9051 eyes of 4784 children were analyzed. The mean±SD and 95% confidence intervals (in parentheses) of vertical cup-to-disc ratio, average cup-to-disc ratio, rim area, disc area, and cup volume were 0.45±0.15(0.45–0.46) mm, 0.43±0.14 (0.42–0.43) mm, 1.46±0.25 (1.45–1.47) mm2, 1.92±0.35 (1.91–1.93) mm2, and 0.14±0.14 (0.14–0.15) mm3, respectively. Vertical cup-to-disc ratio and average cup-to-disc ratio had a positive association with intraocular pressure (IOP) (both βs=0.003), and a negative association with retinal nerve fiber layer thickness (both βs=−0.001), central corneal thickness (CCT) (both βs=−0.001), anterior chamber depth (β=−0.025 and β=−0.027, respectively), lens thickness (β=−0.034 and β=−0.032, respectively), and mean keratometry (MK) (both βs=−0.015). The average cup-to-disc ratio had a positive association with height (β=0.001). Rim area had a negative association with increased age (β=−0.008), axial length (β=−0.065), IOP (β=−0.009), and MK (β=−0.014) and a positive association with macular volume (β=0.021), retinal nerve fiber layer thickness (β=0.004), and CCT (β=0.001). Disc area had a positive association with macular volume (β=0.031) and a negative association with female sex (β=−0.037), axial length (β=−0.087), anterior chamber depth (β=−0.112), lens thickness (β=−0.059), and MK (β=−0.048). The results of generalized estimating equations showed that cup volume was smaller in girls (β=−0.009), and had a positive association with height (β=0.001), IOP (β=0.003) and negative association with CCT (β=−0.0001) and MK (β=−0.012).

Conclusion:

The results provided the normative values of optic disc indices in children. Demographic factors, biometric components, IOP, SBP, and retinal parameters had a significant association with optic disc indices.
Acceptance and Benefit of Electroacoustic Stimulation in Children
Authors: Spitzer Emily R. , Kay-Rivest Emily , Waltzman Susan B. , O'Brien Colleen A. , Santacatterina Michele , Roland J. Thomas , Landsberger David M. , Friedmann David R
Published: April 2023

Objective

Children with high-frequency severe-to-profound hearing loss and low-frequency residual hearing who do not derive significant benefit from hearing aids are now being considered for cochlear implantation. Previous research shows that hearing preservation is possible and may be desirable for the use of electroacoustic stimulation (EAS) in adults, but this topic remains underexplored in children. The goal of this study was to explore factors relating to hearing preservation, acceptance, and benefits of EAS for children.

Study Design

Retrospective review.

Setting

Tertiary academic medical center.

Patients

Forty children (48 ears) with preoperative low-frequency pure-tone averages of 75 dB HL or less at 250 and 500 Hz (n = 48).

Intervention

All patients underwent cochlear implantation with a standard-length electrode.

Main Outcome Measure

Low-frequency audiometric thresholds, speech perception, and EAS usage were measured at initial stimulation, and 3 and 12 months postoperatively. Outcomes were compared between children with and without hearing preservation, and between EAS users and nonusers.

Results

Hearing was preserved at similar rates as adults but worse for children with an enlarged vestibular aqueduct. Fewer than half of children who qualified to use EAS chose to do so, citing a variety of audiologic and nonaudiologic reasons. No differences were detected in speech perception scores across the groups for words, sentences, or sentences in noise tests.

Conclusions

Neither hearing preservation nor EAS use resulted in superior speech perception in children with preoperative residual hearing; rather, all children performed well after implantation.
Racial and Ethnic Disparities in Opioid Prescriptions in Benign and Malignant Pancreatic Disease in the United States
Authors: McHenry Nicole , Ahmed Awais , Shah Ishani , Freedman Steven D. , Nee Judy , Lembo Anthony , Sheth Sunil G.
Published: April 2023

Objectives

Racial-ethnic disparities in pain management are common but not known among pancreatic disease patients. We sought to evaluate racial-ethnic disparities in opioid prescriptions for pancreatitis and pancreatic cancer patients.

Methods

Data from the National Ambulatory Medical Care Survey were used to examine racial-ethnic and sex differences in opioid prescriptions for ambulatory visits by adult pancreatic disease patients.

Results

We identified 207 pancreatitis and 196 pancreatic cancer patient visits, representing 9.8 million visits, but weights were repealed for analysis. No sex differences in opioid prescriptions were found among pancreatitis (P = 0.78) or pancreatic cancer patient visits (P = 0.57). Opioids were prescribed at 58% of Black, 37% of White, and 19% of Hispanic pancreatitis patient visits (P = 0.05). Opioid prescriptions were less common in Hispanic versus non-Hispanic pancreatitis patients (odds ratio, 0.35; 95% confidence interval, 0.14–0.91; P = 0.03). We found no racial-ethnic differences in opioid prescriptions among pancreatic cancer patient visits.

Conclusions

Racial-ethnic disparities in opioid prescriptions were observed in pancreatitis, but not pancreatic cancer patient visits, suggesting possible racial-ethnic bias in opioid prescription practices for patients with benign pancreatic disease. However, there is a lower threshold for opioid provision in the treatment of malignant, terminal disease.
Preoperative Rapid Weight Loss as a Prognostic Predictor After Surgical Resection for Pancreatic Cancer
Authors: Nishikawa Makoto , Yamamoto Junji , Einama Takahiro , Hoshikawa Mayumi , Iwasaki Toshimitsu , Nakazawa Akiko , Takihara Yasuhiro , Tsunenari Takazumi , Kishi Yoji
Published: April 2023

Objective

The aim of the study is to evaluate the influence of cachexia at the time of diagnosis of pancreatic ductal adenocarcinoma (PDAC) on prognosis in patients undergoing surgical resection.

Methods

Patients with data on preoperative body weight (BW) change followed by surgical resection during 2008–2017 were selected. Large BW loss was defined as weight loss >5% or >2% in individuals with body mass index less than 20 kg/m2 within 1 year preoperatively. Influence of large BW loss, ΔBW defined as preoperative BW change (%) per month, prognostic nutrition index, and indices of sarcopenia.

Results

We evaluated 165 patients with PDAC. Preoperatively, 78 patients were categorized as having large BW loss. ΔBW was ≤ −1.34% per month (rapid) and > −1.34% per month (slow) in 95 and 70 patients, respectively. The median postoperative overall survival of rapid and slow ΔBW groups was 1.4 and 4.4 years, respectively (P < 0.001). In multivariate analyses rapid ΔBW (hazard ratio [HR], 3.88); intraoperative blood loss ≥430 mL (HR, 1.89); tumor size ≥2.9 cm (HR, 1.74); and R1/2 resection (HR, 1.77) were independent predictors of worse survival.

Conclusions

Preoperative rapid BW loss ≥1.34% per month was an independent predictor of worse survival of patients with PDAC.
A Subset of Pancreatoblastomas May Arise From an Adenomatous Precursor
Authors: Slack Jonathan C. , Bründler Marie-Anne , Box Adrian , Koro Konstantin
Published: April 2023

Pancreatoblastomas are rare pediatric tumors. In adults, they are exceedingly rare and seem to have a worse prognosis. Most are sporadic, though rare, cases occur in patients with familial adenomatous polyposis. Unlike pancreatic ductal adenocarcinomas, pancreatoblastomas are not believed to arise from dysplastic precursor lesions. Clinical history, along with endoscopic, pathological, and molecular findings, was reviewed for a 57-year-old male patient with an ampullary mass who presented with obstructive jaundice. Microscopic examination showed a pancreatoblastoma subjacent to an adenomatous polyp with intestinal differentiation and low-grade dysplasia. Both tumors had abnormal p53 (complete loss) and nuclear β-catenin immunostaining. Mutational panel analysis showed an identical CTNNB1 (p.S45P) mutation in both. This case adds to our understanding of the pathogenesis of these rare tumors and suggests that a subset may arise from an adenomatous precursor. In addition, this case is just the second pancreatoblastoma to originate in the duodenal ampulla, and the preceding case suggests that an ampullary location leads to earlier diagnosis. Moreover, this case highlights the difficulty in diagnosing pancreatoblastoma on limited tissue specimens and illustrates the need to include pancreatoblastoma in the differential diagnosis in all tumors in and around the pancreas, including those in adult patients.
Pancreatic Neuroendocrine Tumor: Rationale for Centralization in an Integrated Health Care System
Authors: Kwak Hyunjee V. , Hsu Diana S. , Le Sidney T. , Chang Alex L. , Spitzer Austin L. , Kazantsev George B. , Peng Peter D. , Chang Ching-Kuo
Published: April 2023

Objectives

Given the complex surgical management and infrequency of pancreatic neuroendocrine tumor, we hypothesized that treatment at a center of excellence improves survival.

Methods

Retrospective review identified 354 patients with pancreatic neuroendocrine tumor treated between 2010 and 2018. Four hepatopancreatobiliary centers of excellence were created from 21 hospitals throughout Northern California. Univariate and multivariate analyses were performed. The χ2 test of clinicopathologic factors determined which were predictive for overall survival (OS).

Results

Localized disease was seen in 51% of patients, and metastatic disease was seen in 32% of patients with mean OS of 93 and 37 months, respectively (P < 0.001). On multivariate survival analysis, stage, tumor location, and surgical resection were significant for OS (P < 0.001). All stage OS for patients treated at designated centers was 80 and 60 months for noncenters (P < 0.001). Surgery was more common across stages at the centers of excellence versus noncenters at 70% and 40%, respectively (P < 0.001).

Conclusions

Pancreatic neuroendocrine tumors are indolent but have malignant potential at any size with management often requiring complex surgeries. We showed survival was improved for patients treated at a center of excellence, where surgery was more frequently utilized.
Overwork Among ICU Nurses
Authors: Xie Tian , He Wenhao , Jiu Zhaohua , Li Qixia , Huang Changyang , Liu Jiali , Sun Zhongwen , Zhang Huiting
Published: April 2023

OBJECTIVE

This study aimed to describe the current situation and explore overwork predictors among ICU nurses in China.

BACKGROUND

Overwork is a comprehensive condition of labor where employees work for extended periods with high intensity and high pressure, which can negatively affect their health. Limited literature exists regarding the prevalence, characteristics, professional identity, and environment of overwork among ICU nurses.

METHODS

A cross-sectional design study was conducted. The Professional Identification Scale for Nurses, the Practice Environment Scale of the Nursing Work Index, and the Overwork Related Fatigue Scale (ORFS) were used. To explore relationships between variables, univariate analysis or bivariate correlations were used. Multiple regression was used to identify predictors of overwork.

RESULTS

Almost 85% of nurses were categorized as overworked, of which, 30% were moderately to severely overworked. Gender, form of employment, stress related to ICU nursing technology and equipment updates, nurses' professional identity, and nurse working environment accounted for 36.6% in the ORFS.

CONCLUSIONS

Overwork is common among ICU nurses. Nurse managers need to develop and implement strategies to better support nurses to prevent overwork.
A Case of Recessive Dystrophic Epidermolysis Bullosa Associated Colitis
Authors: McCann Katelyn , Wiss Karen , Covington Jeffrey , Laffert Vanessa , Gosselin Kerri B.
Published: April 2023

Recessive dystrophic epidermolysis bullosa (EB) is a rare disease characterized by painful blistering and erosion of the skin, sometimes referred to as “butterfly skin disease” because patients’ skin becomes as fragile as butterfly wings. In addition to severe dermatologic manifestations, EB patients also experience complications affecting epithelial surfaces including the gastrointestinal tract. While gastrointestinal complications such as oral mucosal ulceration, esophageal strictures, constipation, and gastroesophageal reflux are common in EB patients, reports of colitis are rare. Here we describe a patient with recessive dystrophic EB who developed EB-associated colitis. This case highlights the diagnostic challenges as well as the gaps in our current understanding of the prevalence, pathogenesis, and treatment of EB-associated colitis.
Homology of homologous knotted proteins
Authors: Benjamin Katherine , Mukta Lamisah , Moryoussef Gabriel , Uren Christopher , Harrington Heather A. , Tillmann Ulrike , Barbensi Agnese
Published: April 2023

Quantification and classification of protein structures, such as knotted proteins, often requires noise-free and complete data. Here, we develop a mathematical pipeline that systematically analyses protein structures. We showcase this geometric framework on proteins forming open-ended trefoil knots, and we demonstrate that the mathematical tool, persistent homology, faithfully represents their structural homology. This topological pipeline identifies important geometric features of protein entanglement and clusters the space of trefoil proteins according to their depth. Persistence landscapes quantify the topological difference between a family of knotted and unknotted proteins in the same structural homology class. This difference is localized and interpreted geometrically with recent advancements in systematic computation of homology generators. The topological and geometric quantification we find is robust to noisy input data, which demonstrates the potential of this approach in contexts where standard knot theoretic tools fail.
Scattering of elastic waves by a sphere with cubic anisotropy with application to attenuation in polycrystalline materials
Authors: Jafarzadeh Ata , Folkow Peter D. , Boström Anders
Published: April 2023

Scattering of elastic waves by an anisotropic sphere with cubic symmetry inside an isotropic medium is studied. The waves in the isotropic surrounding are expanded in the spherical vector wave functions. Inside the sphere, the elastodynamic equations are first transformed to spherical coordinates and the displacement field is expanded in terms of the vector spherical harmonics in the angular directions and a power series in the radial direction. The governing equations inside the sphere give recursion relations among the expansion coefficients in the power series. The boundary conditions on the sphere then determine the expansion coefficients of the scattered wave. This determines the transition (

T

) matrix elements which are calculated explicitly to the leading order for low frequencies. Using the theory of Foldy, the

T

matrix elements of a single sphere are used to study attenuation and phase velocity of polycrystalline materials with cubic symmetry, explicitly for low frequencies and numerically for intermediate frequencies. Numerical comparisons of the present method with previously published results and recent finite element method (FEM) results show a good correspondence for low and intermediate frequencies. The present approach shows a better agreement with FEM for strongly anisotropic materials in comparison with other published methods.
Spatially quasi-periodic water waves of finite depth
Authors: Wilkening Jon , Zhao Xinyu
Published: April 2023

We present a numerical study of spatially quasi-periodic gravity-capillary waves of finite depth in both the initial value problem and travelling wave settings. We adopt a quasi-periodic conformal mapping formulation of the Euler equations, where one-dimensional quasi-periodic functions are represented by periodic functions on a higher-dimensional torus. We compute the time evolution of free surface waves in the presence of a background flow and a quasi-periodic bottom boundary and observe the formation of quasi-periodic patterns on the free surface. Two types of quasi-periodic travelling waves are computed: small-amplitude waves bifurcating from the zero-amplitude solution and larger-amplitude waves bifurcating from finite-amplitude periodic travelling waves. We derive weakly nonlinear approximations of the first type and investigate the associated small-divisor problem. We find that waves of the second type exhibit striking nonlinear behaviour, e.g. the peaks and troughs are shifted non-periodically from the corresponding periodic waves due to the activation of quasi-periodic modes.
Assessing the impact of fire on spiders through a global comparative analysis
Authors: McLean Claire A. , Melville Jane , Schubert Joseph , Rose Rebecca , Medina Iliana
Published: April 2023

In many regions fire regimes are changing due to anthropogenic factors. Understanding the responses of species to fire can help to develop predictive models and inform fire management decisions. Spiders are a diverse and ubiquitous group and can offer important insights into the impacts of fire on invertebrates and whether these depend on environmental factors, phylogenetic history or functional traits. We conducted phylogenetic comparative analyses of data from studies investigating the impacts of fire on spiders. We investigated whether fire affects spider abundance or presence and whether ecologically relevant traits or site-specific factors influence species’ responses to fire. Although difficult to make broad generalizations about the impacts of fire due to variation in site- and fire-specific factors, we find evidence that short fire intervals may be a threat to some spiders, and that fire affects abundance and species compositions in forests relative to other vegetation types. Orb and sheet web weavers were also more likely to be absent after fire than ambush hunters, ground hunters and other hunters suggesting functional traits may affect responses. Finally, we show that analyses of published data can be used to detect broad-scale patterns and provide an alternative to traditional meta-analytical approaches.
The power of peer networking for improving STEM faculty job applications: a successful pilot programme
Authors: Guardia Carlos M. , Kane Erin , Tebo Alison G. , Sanders Anna A. W. M. , Kaya Devrim , Grogan Kathleen E.
Published: April 2023

To attain a faculty position, postdoctoral fellows submit job applications that require considerable time and effort to produce. Although mentors and colleagues review these applications, postdocs rarely receive iterative feedback from reviewers with the breadth of expertise typically found on an academic search committee. To address this gap, we describe an international peer-reviewing programme for postdocs across disciplines to receive reciprocal, iterative feedback on faculty applications. A participant survey revealed that nearly all participants would recommend the programme to others. Furthermore, our programme was more likely to attract postdocs who struggled to find mentoring, possibly because of their identity as a woman or member of an underrepresented population in STEM or because they changed fields. Between 2018 and 2021, our programme provided nearly 150 early career academics with a diverse and supportive community of peer mentors during the difficult search for a faculty position and continues to do so today. As the transition from postdoc to faculty represents the largest ‘leak’ in the academic pipeline, implementation of similar programmes by universities or professional societies would provide psycho-social support necessary to prevent attrition of individuals from underrepresented populations as well as increase the chances of success for early career academics in their search for independence.
A Case Report of disseminated Streptococcus pneumoniae infection complicated by infective endocarditis, septic arthritis and epidural abscess in an immunocompetent patient
Authors: Dean Kimberley Rose , Koirala Archana , Samarasekara Harsha
Published: April 2023

Streptococcus pneumoniae is a highly virulent, vaccine preventable pathogen which can cause disease on a spectrum from benign to fatal. Apart from pneumonia, it commonly causes septicaemia and meningitis. This case report describes an unusual range of complications in a middle, aged Caucasian female presenting to a regional hospital, without any risk known factors for severe disease. Progressing from episode of otitis media, her condition rapidly progressed to mastoid sinusitis, septic arthritis, infective endocarditis epidural abscesses and multiple subcutaneous abscesses. Following quick identification of S pneumoniae from a positive blood culture, she was treated with high dose benzylpenicillin and ceftriaxone and aggressive source control by surgery, enabling a good clinical recovery.
Taking hospital pathogen surveillance to the next level
Authors: Werner Guido , Couto Natacha , Feil Edward J. , Novais Angela , Hegstad Kristin , Howden Benjamin P. , Friedrich Alexander W. , Reuter Sandra
Published: April 2023

High-throughput bacterial genomic sequencing and subsequent analyses can produce large volumes of high-quality data rapidly. Advances in sequencing technology, with commensurate developments in bioinformatics, have increased the speed and efficiency with which it is possible to apply genomics to outbreak analysis and broader public health surveillance. This approach has been focused on targeted pathogenic taxa, such as Mycobacteria, and diseases corresponding to different modes of transmission, including food-and-water-borne diseases (FWDs) and sexually transmitted infections (STIs). In addition, major healthcare-associated pathogens such as methicillin-resistant

Staphylococcus aureus

, vancomycin-resistant enterococci and carbapenemase-producing

Klebsiella pneumoniae

are the focus of research projects and initiatives to understand transmission dynamics and temporal trends on both local and global scales. Here, we discuss current and future public health priorities relating to genome-based surveillance of major healthcare-associated pathogens. We highlight the specific challenges for the surveillance of healthcare-associated infections (HAIs), and how recent technical advances might be deployed most effectively to mitigate the increasing public health burden they cause.
Network connectivity and local transcriptomic vulnerability underpin cortical atrophy progression in Parkinson's disease
Authors: Vo Andrew , Tremblay Christina , Rahayel Shady , Shafiei Golia , Hansen Justine Y , Yau Yvonne , Misic Bratislav , Dagher Alain
Published: April 2023

Parkinson's disease pathology is hypothesized to spread through the brain via axonal connections between regions and further modulated by local vulnerabilities within those regions. The resulting changes to brain morphology have previously been demonstrated in both prodromal and de novo Parkinson's disease patients. However, it remains unclear whether the pattern of atrophy progression in Parkinson's disease over time is similarly explained by network-based spreading and selective vulnerability. We address this gap by mapping the trajectory of cortical atrophy rates in a large, multi-centre cohort of Parkinson's disease patients and related this atrophy progression pattern to network architecture and gene expression profiles. Across 4-year follow-up visits, increased atrophy rates were observed in posterior, temporal, and superior frontal cortices. We demonstrated that this progression pattern was shaped by network connectivity. Regional atrophy rates were strongly related to atrophy rates across structurally and functionally connected regions. We also found that atrophy progression was associated with specific gene expression profiles. The genes most related to atrophy rates were those enriched for mitochondrial and metabolic function. Taken together, our findings demonstrate that both global and local brain features influence vulnerability to neurodegeneration in Parkinson's disease.
Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
Authors: Dueñas Nuria , Klinkhammer Hannah , Bonifaci Nuria , Spier Isabel , Mayr Andreas , Hassanin Emadeldin , Díez-Villanueva Anna , Moreno Victor , Pineda Marta , Maj Carlo , Capellá Gabriel , Aretz Stefan , Brunet Joan
Published: April 2023

Background

Polygenic risk scores (PRS) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant LS individuals.

Methods

1,465 LS individuals (557MLH1, 517MSH2/EPCAM, 299MSH6, and 92PMS2)and 5,656 CRC-free population-based controls from two independent cohorts were included. A 91-Single Nucleotide Polymorphism PRS was applied. A Cox proportional hazard regression model with “family” as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted.

Results

Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed < 50 years, and in individuals with multiple CRCs or AAs diagnosed < 60 years.

Conclusion

The PRS may slightly influence CRC risk in LS individuals, in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.

KEY MESSAGES

WHAT IS ALREADY KNOWN ON THIS TOPIC?

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Great variability in the incidence of CRC has been described in LS individuals, even within the same family.

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Polygenic risk scores (PRS) can help stratify colorectal cancer risk and, thus, adjust surveillance or treatment procedures.

WHAT THIS STUDY ADDS

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PRS performed on family-based registries slightly influences CRC risk in subgroups of LS individuals, even though with weak effects.

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Our study showed a weak association of PRS with multiple and young CRC cases, pointing to a possible risk-modifying role in extreme phenotypes.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

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Gene-based PRS analysis and its combination with other genetic and non-genetic factors may contribute to refining cancer risk in LS patients.
ChatGPT as a medical doctor? A diagnostic accuracy study on common and rare diseases
Authors: Mehnen Lars , Gruarin Stefanie , Vasileva Mina , Knapp Bernhard
Published: April 2023

Seeking medical advice online has become popular in the recent past. Therefore a growing number of people might ask the recently hyped ChatGPT for medical information regarding their conditions, symptoms and differential diagnosis. In this paper we tested ChatGPT for its diagnostic accuracy on a total of 50 clinical case vignettes including 10 rare case presentations. We found that ChatGPT 4 solves all common cases within 2 suggested diagnoses. For rare disease conditions ChatGPT 4 needs 8 or more suggestions to solve 90% of all cases. The performance of ChatGPT 3.5 is consistently lower than the performance of ChatGPT 4. We also compared the performance between ChatGPT and human medical doctors. We conclude that ChatGPT might be a good tool to assist human medical doctors in diagnosing difficult cases, but despite the good diagnostic accuracy, ChatGPT should be used with caution by non-professionals.
Deviation from Nash Mixed Equilibrium in Repeated Rock-Scissors-Paper Reflect Individual Personality Traits
Authors: Arai Kensuke , Jacob Suma , Widge Alik S. , Yousefi Ali
Published: April 2023

Quantification of human behavior in a social context can reveal behavioral variations in a population that can be used to improve screening and targeting accuracy in the development of interventions and biomedical treatments for psychiatric disorders. However, social interaction is difficult to study and quantify in a controlled, reproducible environment. In this research, we describe an experimental framework that utilizes a zero-sum game of repeated Rock-Paper-Scissors played against an artificial intelligence agent to probe social interaction. Human deviation from the Nash Mixed Equilibrium strategy of play, the only guaranteed way to avoid exploitation, can be seen in the sequential dependence of hands. We hypothesize that this deviation represents humans mimicing randomness through constant adjustments of behavior, which we analyze in terms of a set of switching heuristic lag-1 conditional response rules. We quantify and interpret the set of rules subjects are able to utilize as mirroring individual personality traits of the subjects. Subjects in the study also completed the Autism Quotient Abridged survey, and subscores of the social, imagination and routine dimensions were found to be predicted by a combination of behavioral features derived from game play. This work proposes a new approach to quantifying social behavioral traits in individuals affected by psychiatric disorders that manifest in social functioning.
Ebola Virus Sequesters IRF3 in Viral Inclusion Bodies to Evade Host Antiviral Immunity
Authors: Zhu Lin , Jin Jing , Wang Tingting , Hu Yong , Liu Hainan , Gao Ting , Dong Qincai , Jin Yanwen , Li Ping , Liu Zijing , Huang Yi , Liu Xuan , Cao Cheng
Published: April 2023

Viral inclusion bodies (IBs) commonly form during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK-1) or IκB kinase epsilon (IKKε), was recruited and sequestered in viral IBs when the cells were infected by EBOV transcription- and replication-competent virus-like particles (trVLPs). NP/VP35-induced IBs formation was critical for IRF3 recruitment and sequestration, probably through interaction with STING. Consequently, the association of TBK1 and IRF3, which plays a vital role in type I interferon (IFN-I) induction, was blocked by EBOV trVLPs infection. Additionally, IRF3 phosphorylation and nuclear translocation induced by Sendai virus (SeV) or poly(I:C) stimulation were suppressed by EBOV trVLPs. Furthermore, downregulation of STING significantly attenuated VP35-induced IRF3 accumulation in IBs. Coexpression of the viral proteins by which IBs-like structures formed was much more potent in antagonizing IFN-I than expression of the IFN-I antagonist VP35 alone. These results suggested a novel immune evasion mechanism by which EBOV evades host innate immunity.

Impact statement

Ebola virus VP35 protein evades host antiviral immunity by interacting with STING to sequester IRF3 into inclusion bodies and inhibit type-I interferon production.
Systematic evaluation of the two main blood-based RNA-seq approaches for Mendelian disease diagnosis
Authors: Yang Ziying , Yang Xiaoru , Chen Yunmei , Wang Zhonghua , Song Lijie , Sun Jun , Peng Huanhuan , Yang Xunzhe , Peng Zhiyu , Dai Yi
Published: April 2023

Background

As an adjunct to diagnostic exome sequencing and whole-genome sequencing, RNA sequencing (RNA-seq) has been demonstrated to improve diagnostic yield for Mendelian diseases. However, systematic evaluation of the associated experimental and computational processes and the establishment of robust and efficient practices for RNA diagnostics implemented in the clinic to analyse readily accessible whole blood samples are still required.

Methods

We simulated clinical conditions in which each patient’s sample is tested only once, and we evaluated the two typical experimental protocols (polyA-selection and rRNA depletion) by comparing the expression profiles, aberrant splicing events and monoallelic expression (MAE) identified from 11 patients in clinical settings with different bioinformatics software.

Results

We demonstrated that a higher proportion of unique reads from polyA-selection than rRNA depletion were mapped to exons or exon – intron junction regions (84.54% vs. 40.14%), resulting in more detectable OMIM genes (TPM > 1) in the blood (65.29% vs. 59.79%); thus, the rRNA depletion method requires a median of 258 more valid reads per gene to achieve the same level of gene quantification. Moreover, although the transcriptome profiling of protein-coding genes in the two methods is highly correlated, polyA-selection offers more sensitive detection of MAE variants and aberrant splicing under common filtering conditions in combination with DROP.

Conclusions

A combination of polyA+ and DROP is recommended when implementing blood-based RNA-seq for the diagnosis of Mendelian diseases in clinical practice, and filtering criteria for aberrant expression, aberrant splicing and MAE variants are suggested for reference.
Racialized experience, biomarkers of lead exposure, and later-life cognition: a mediation analysis
Authors: Jenson Tara E. , Bakulski Kelly M. , Wesp Linda , Dookeran Keith , Driscoll Ira , Kalkbrenner Amy E.
Published: April 2023

We evaluated the role of the neurotoxicant lead (Pb) in mediating racial disparities in later-life cognition in 1,085 non-Hispanic Black and 2,839 non-Hispanic white participants in NHANES (1999-2002, 2011-2014) 60+ years of age. We operationalized Black race as a marker for the experience of racialization and exposure to systemic racism. We estimated patella bone Pb via predictive models using blood Pb and demographics. Concurrent cognition (processing speed, sustained attention, working memory) was measured by the Digit Symbol Substitution Test (DSST) and a global measure combining four cognitive tests. To obtain the portion mediated, we used regression coefficients (race on Pb * Pb on cognitive score)/(race on cognitive score), adjusting for age, NHANES cycle, and sample weights. Other confounder adjustment (education, poverty income ratio, smoking) was limited to the mediator-outcome (i.e., Pb-cognition) pathway because these factors do not lie upstream of race and so cannot confound associations with race. Pb was estimated to mediate 0.6% of the association between race and global cognition, and 4% of the DSST. Our results suggest that later-life cognitive health disparities may be impacted by avoidable lead exposure driven by environmental injustice, noting that a large proportion of the pathway of systemic racism harming cognition remains.