bluuebunny/crossref_metadata_2025 huggingface dataset:
The Psychometric Properties of the 9-Item Vestibular Activities Avoidance Instrument
Authors: Dunlap Pamela M , Alradady Fai A , Costa Claudia M , Delitto Anthony , Terhorst Lauren , Sparto Patrick J , Furman Joseph M , Marchetti Gregory F , Staab Jeffrey P , Chueh Jasmine , Whitney Susan L
Published: July 2023

Objective

The purpose of this study was to establish the psychometric properties of the 9-Item Vestibular Activities Avoidance Instrument (VAAI-9), a patient-reported outcome measure developed to identify fear avoidance beliefs in persons with vestibular disorders.

Methods

This prospective cohort study included 100 participants 18 years and older seeking care at a balance disorders clinic for dizziness. Participants completed the VAAI-9, the Dizziness Handicap Inventory (DHI), and other patient-reported outcomes at the initial visit and the 3-month follow-up. To measure test–retest reliability, the VAAI-9 was completed again 5 days after the initial visit and was analyzed using a 2-way mixed ICC for absolute agreement. Internal consistency was determined using the Cronbach alpha. The Spearman correlation coefficient was used to assess convergent validity of the VAAI-9 with other outcomes. Receiver operating characteristic curves were used to identify baseline VAAI-9 cutoff scores for those who reported mild (DHI ≤ 30) or moderate or severe (DHI > 30) perceived disability at the 3-month follow-up.

Results

The mean age of the study cohort was 49 (SD = 16) years; 73 (73%) were women. Seventy-one participants completed the 5-day follow-up, and 68 completed the 3-month follow-up. The VAAI-9 demonstrated excellent internal consistency (α = 0.91) and test–retest reliability (ICC = 0.90). Baseline VAAI-9 scores had moderate to strong associations with other outcome measures at baseline and 3 months. A baseline VAAI-9 score of 26 or higher had a sensitivity of 80.6% and a specificity of 78.4% for identifying a DHI score of >30 at 3 months (area under the curve = 0.86).

Conclusions

The results provide evidence of excellent reliability and validity for the 9-item VAAI in persons with vestibular disorders. A baseline VAAI-9 score of ≥26 identified individuals at risk of persistent moderate to severe disability due to dizziness.

Impact

Initial levels of fear avoidance beliefs measured using the VAAI-9 provided important prognostic information about outcomes for persons with vestibular symptoms.
ChatGPT in the higher education environment: perspectives from the theory of high order thinking skills
Authors: Putra Febri W , Rangka Itsar B , Aminah Siti , Aditama Mint H R
Published: July 2023

ChatGPT is a form of technological progress in the 5.0 era. The use of ChatGPT has begun to penetrate all fields of science, including the field of education. Students use ChatGPT to help them complete their assignments in the university environment. Apart from providing many benefits, ChatGPT also has many dangers threatening students. One of the dangers for students who rely too much on ChatGPT is a decrease in higher-order thinking skills.
The Effect of Wealth on Worker Productivity
Authors: Eeckhout Jan , Sepahsalari Alireza
Published: July 2023

We propose a theory that analyzes how a workers’ asset holdings affect their job productivity. In a labor market with uninsurable risk, workers choose to direct their job search trading off productivity and wages against unemployment risk. Workers with low asset holdings have a precautionary job search motive, they direct their search to low productivity jobs because those offer a low risk at the cost of low productivity and a low wage. Our main theoretical contribution shows that the presence of consumption smoothing can reconcile the directed search model with negative duration-dependence on wages, a robust empirical regularity that the canonical directed search model cannot rationalize. We calibrate the infinite horizon economy and find this mechanism to be quantitatively important. We evaluate a tax financed unemployment insurance (UI) scheme and analyze how it affects welfare. Aggregate welfare is inverted U-shaped in benefits: the insurance effect UI dominates the incentive effects for low levels of benefits and vice versa for high benefits. In addition, when UI increases, total production falls in the economy while worker productivity increases.
Nucleotide Substitution Model Selection Is Not Necessary for Bayesian Inference of Phylogeny With Well-Behaved Priors
Authors: Guimarães Fabreti Luiza , Höhna Sebastian
Published: July 2023

Model selection aims to choose the most adequate model for the statistical analysis at hand. The model must be complex enough to capture the complexity of the data but should be simple enough not to overfit. In phylogenetics, the most common model selection scenario concerns selecting an adequate substitution and partition model for sequence evolution to infer a phylogenetic tree. Previously, several studies showed that substitution model under-parameterization can bias phylogenetic studies. Here, we explored the impact of substitution model over-parameterization in a Bayesian statistical framework. We performed simulations under the simplest substitution model, the Jukes–Cantor model, and compare posterior estimates of phylogenetic tree topologies and tree length under the true model to the most complex model, the $\text{GTR}+\Gamma+\text{I}$ substitution model, including over-splitting the data into additional subsets (i.e., applying partitioned models). We explored 4 choices of prior distributions: the default substitution model priors of MrBayes, BEAST2, and RevBayes and a newly devised prior choice (Tame). Our results show that Bayesian inference of phylogeny is robust to substitution model over-parameterization and over-partitioning but only under our new prior settings. All 3 current default priors introduced biases for the estimated tree length. We conclude that substitution and partition model selection are superfluous steps in Bayesian phylogenetic inference pipelines if well-behaved prior distributions are applied and more effort should focus on more complex and biologically realistic substitution models.
Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial
Authors: McEvoy Cindy T. , Shorey-Kendrick Lyndsey E. , Milner Kristin , Harris Julia , Vuylsteke Brittany , Cunningham Michelle , Tiller Christina , Stewart Jaclene , Schilling Diane , Brownsberger Julie , Titus Hope , MacDonald Kelvin D. , Gonzales David , Vu Annette , Park Byung S. , Spindel Eliot R. , Morris Cynthia D. , Tepper Robert S.
Published: July 2023

(Abstracted from JAMA Pediatr 2023;177(1):16–24)

Despite antismoking efforts, more than 10% of individuals in the United States smoke during pregnancy. This in utero smoke exposure affects more than 400,000 infants per year and puts them at risk for impaired fetal lung function, decreased airway function, and increased risk for wheeze and asthma.
Chronic spontaneous urticaria: new evidences on the role of autoimmunity
Authors: Xiang Yi-Kui , Guloglu Sercan , Elieh-Ali-Komi Daniel , Kocatürk Emek
Published: July 2023

Purpose of review

The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU).

Recent findings

Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors.

Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU.
Role of the ocular surface microbiome in allergic eye diseases
Authors: Cavuoto Kara M. , Galor Anat , Zhu Angela Y.
Published: July 2023

Purpose of review

The purpose of this review is to provide an update on emerging literature on the role of the ocular surface microbiome (OSM) in allergic eye diseases.

Recent findings

Findings in the literature suggest that the ocular surface microbiome plays a role in the pathophysiology and course of allergic disease of the ocular surface.

Knowledge regarding the role of the ocular surface microbiome in allergic disease is important to guide development of targets for future therapeutic interventions.
Hypertension and NAFLD risk: Insights from the NHANES 2017–2018 and Mendelian randomization analyses
Authors: Yuan Mengqin , He Jian , Hu Xue , Yao Lichao , Chen Ping , Wang Zheng , Liu Pingji , Xiong Zhiyu , Jiang Yingan , Li Lanjuan
Published: July 2023

Background:

Hypertension and non-alcoholic fatty liver disease (NAFLD) share several pathophysiologic risk factors, and the exact relationship between the two remains unclear. Our study aims to provide evidence concerning the relationship between hypertension and NAFLD by analyzing data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 and Mendelian randomization (MR) analyses.

Methods:

Weighted multivariable-adjusted logistic regression was applied to assess the relationship between hypertension and NAFLD risk by using data from the NHANES 2017–2018. Subsequently, a two-sample MR study was performed using the genome-wide association study (GWAS) summary statistics to identify the causal association between hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and NAFLD. The primary inverse variance weighted (IVW) and other supplementary MR approaches were conducted to verify the causal association between hypertension and NAFLD. Sensitivity analyses were adopted to confirm the robustness of the results.

Results:

A total of 3144 participants were enrolled for our observational study in NHANES. Weighted multivariable-adjusted logistic regression analysis suggested that hypertension was positively related to NAFLD risk (odds ratio [OR] = 1.677; 95% confidence interval [CI], 1.159–2.423). SBP ≥130 mmHg and DBP ≥80 mmHg were also significantly positively correlated with NAFLD. Moreover, hypertension was independently connected with liver steatosis (β = 7.836 [95% CI, 2.334–13.338]). The results of MR analysis also supported a causal association between hypertension (OR = 7.203 [95% CI, 2.297–22.587]) and NAFLD. Similar results were observed for the causal exploration between SBP (OR = 1.024 [95% CI, 1.003–1.046]), DBP (OR = 1.047 [95% CI, 1.005–1.090]), and NAFLD. The sensitive analysis further confirmed the robustness and reliability of these findings (all P >0.05).

Conclusion:

Hypertension was associated with an increased risk of NAFLD.
Regenerative Peripheral Nerve Interface Surgery: Anatomic and Technical Guide
Authors: Leach Garrison A. , Dean Riley A. , Kumar Nishant Ganesh , Tsai Catherine , Chiarappa Frank E. , Cederna Paul S. , Kung Theodore A. , Reid Chris M.
Published: July 2023

Regenerative peripheral nerve interface (RPNI) surgery has been demonstrated to be an effective tool as an interface for neuroprosthetics. Additionally, it has been shown to be a reproducible and reliable strategy for the active treatment and for prevention of neuromas. The purpose of this article is to provide a comprehensive review of RPNI surgery to demonstrate its simplicity and empower reconstructive surgeons to add this to their armamentarium. This article discusses the basic science of neuroma formation and prevention, as well as the theory of RPNI. An anatomic review and discussion of surgical technique for each level of amputation and considerations for other etiologies of traumatic neuromas are included. Lastly, the authors discuss the future of RPNI surgery and compare this with other active techniques for the treatment of neuromas.
Surgical Correction of Nipple Hypertrophy after Nipple-sparing Mastectomy with Breast Reconstruction
Authors: Kawai Kenichiro , Fujiwara Toshihiro , Nishimoto Soh , Ishise Hisako , Saito Takuya , Nakajima Koyo , Kubo Tateki , Kakibuchi Masao
Published: July 2023

Nipple hypertrophy is a relatively common phenomenon, particularly in the Asian patient population. The incidence and prevalence or cause of nipple hypertrophy are not well defined in the literature. As survival rates for breast cancer patients continue to improve, there is an increasing emphasis on enhancing their quality of life. Treatment options, such as lumpectomy and radiation therapy or mastectomy, now prioritize preservation of the nipple-areolar complex (NAC) through techniques like nipple-sparing mastectomy (NSM). This approach has been shown to improve patient satisfaction and quality of life. However, it is important to note that NSM is associated with certain complications, including NAC necrosis, malposition, and local recurrence of the tumor. Among those complications, nipple hypertrophy is quite rare. In this report, we present a case of nipple hypertrophy that developed after breast reconstruction, using autologous tissue. The patient, a 48-year-old woman, underwent NSM for breast cancer, and had a tissue expander placed simultaneously. Following tissue expansion, breast reconstruction with a deep inferior epigastric perforator (DIEP) flap was performed. However, during the tissue expansion phase, the patient’s nipple gradually enlarged, and the protrusion became more pronounced after the DIEP flap transfer. Nipple reduction surgery was subsequently performed for both diagnostic and cosmetic purposes. We present this case along with a review of relevant literature.
Radon Flux Measurement System
Authors: Caffrey Emily A. , Mangini Colby D. , Rood Arthur S. , Grogan Helen A. , Till John E.
Published: July 2023

Disposal of naturally occurring radioactive material (NORM) and technologically enhanced naturally occurring radioactive material (TENORM) waste in the State of Oregon is prohibited unless it can be demonstrated that the material is nonradioactive as defined by its radionuclide content and potential for emission into the environment. It was determined that a radon flux on the surface of the waste no greater than 0.37 Bq m−2 s−1 would meet this requirement. This article provides a method to estimate the radon flux through indirect measurement of the radon mass exhalation rate. It describes a device that consists of a radon accumulation chamber coupled with a continuous radon monitor and software to process the results and calculate the radon mass exhalation rate and radon flux for an unknown sample of approximately 500 g. The chamber system was tested with a uranium ore sample.
Sealing of clear corneal incisions with autologous blood
Authors: Tak Harshul Kumar
Published: July 2023

The author describes a novel technique of using autologous blood as a sealant to seal clear corneal phacoemulsification incisions, which leak even after stromal hydration at the end of phacoemulsification surgery. Using a 26-gauge, half-inch straight needle, mounted on an empty 2-mL syringe, limbal blood vessels near the leaking incisions are nicked so that mild blood oozes out. Once some blood is collected, this blood is spread over the incision by the property of surface tension using the 26-gauge needle tip and kept there for 20 to 40 seconds. By capillary action, it also seals the microleaks in the incision tunnel and forms a clot at the incision entry.
Genotype–Phenotype and Genotype–Outcome Analysis of Capillary Malformation–Arteriovenous Malformation
Authors: Sun Yi , Su Lixin , Zhang Yunjie , Wang Zhenfeng , Chen Shijie , Gu Hao , Yue Xiaojie , Zhao Xiong , Yang Xitao , Wang Deming , Fan Xindong , Cai Ren
Published: July 2023

Objective(s):

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare autosomal-dominant complex vascular disorder that can be associated with fast-flow vascular malformations (FFVMs). The purpose of this study is to explore the genotype–phenotype and genotype–outcome associations based on a large parallel sequencing of CM-AVM patients to improve the understanding of the development and risk factors for FFVM.

Methods:

A total of 117 patients with CM-AVMs were enrolled in this multicenter cohort study. All patients underwent detailed clinical phenotyping, including age, sex, capillary malformation (CM) size, with or without FFVM, and outcome (Schobinger stage). Next-generation sequencing was performed with peripheral blood and tissue samples. Genotype–phenotype, genotype–outcome, and phenotype–outcome analyses were performed.

Results:

Germline or mosaic RASA1 variants were the most common cause of CM-AVM, found in 61.5%, with EPHB4 variants in 32.5%. A total of 76.9% of patients had a dominant CM lesion larger than 5 cm. No obvious correlations between genotypes and phenotypes, including sex, age, location, and size of CMs, were found in this cohort. Comparing the patients with FFVMs with those without FFVMs, we found significant differences in age and the size of dominant CM lesions but not in genotype, sex, or location.

Conclusion:

CM-AVMs can be categorized as complex vascular malformations caused by different gene alterations in the RAS/RAF/MEK pathway. No obvious correlations between genotypes and phenotypes were identified. Critically, the occurrence and progression of FFVM is strongly determined by phenotypes, including age and the size of the dominant CM, rather than genotypes.
Implementation of Electronic Postoperative Nausea and Vomiting Assessment and Best Practice Advisory Tools to Improve Patient Care
Authors: Pratt Samantha , Howard-Ruben Josie
Published: July 2023

Background:

Postoperative nausea and vomiting (PONV) affects 30% of surgical patients undergoing anesthesia. PONV is a substantial cause of increased length of stay, cost of care, and unanticipated patient admission and readmission.

Local Problem:

Seventy percent of patients received PONV prophylaxis; PONV assessment was performed in only 63% of patients in this hospital system.

Methods:

A standardized PONV preoperative assessment checklist and a best practice advisory (BPA) were implemented in our electronic medical record (EMR) and charting system. Anesthesia providers and postanesthesia care unit (PACU) nurses completed training on patient management for PONV, including preoperative assessment and BPA use.

Results:

The PONV preoperative assessment achieved high adoption, and providers followed its recommendations in more than 90% of cases. During the 6-month implementation phase, PONV rates decreased from 56% to 43.6%.

Conclusions:

Implementing a standardized, electronic PONV preoperative risk assessment checklist and a BPA effectively reduced PONV rates in this hospital system.
Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications (“Sleep C.A.L.M.”) in the Evaluation and Management of Nocturia: A Simple Approach to a Complex Diagnosis
Authors: Monaghan Thomas F. , Weiss Jeffrey P. , Wein Alan J. , Rahman Syed N. , Lazar Jason M. , Bliwise Donald L. , Everaert Karel , Lemack Gary E. , Cornu Jean-Nicolas , Drake Marcus J. , Chapple Christopher R. , Hashim Hashim , Blaivas Jerry G. , Dmochowski Roger R.
Published: July 2023

(Abstracted from Neurourol Urodyn 2023;42:562–572)

The number of times urine is passed during the main sleep period, or nocturia, is a condition based on a fundamentally mismatched relationship between functional bladder storage capacity and nocturnal urine production, modulated by sleep patterns. Although nocturia may be caused by genitourinary tract abnormalities, other factors such as medical diseases, medications, sleep disorders, or modifiable behavioral factors may exert consequences between sleep and urine storage/production.
Pediatric Autoimmune or Primary Sclerosing Cholangitis: Metronidazole Effectiveness on Biochemical Data, Bile Acid Profile, and Gut Microbiota: A Pilot Study
Authors: Karemera Manon , Verce Marko , Roumain Martin , Muccioli Giulio G. , Cani Patrice D. , Everard Amandine , Stephenne Xavier , Sokal Etienne
Published: July 2023

Objectives:

Autoimmune hepatitis and primary sclerosing cholangitis (PSC) can both be present, resulting in autoimmune sclerosing cholangitis (ASC). PSC physiopathology could be based on the cross-talk between gut microbiota and bile acids (BAs); antibiotics are an innovative therapy. This pilot study assesses metronidazole (MTZ)’s effectiveness in ASC or PSC patients according to the stage of the disease, and its effects on biochemical parameters, BA profiles, and gut microbiota.

Methods:

ASC or PSC patients from Cliniques universitaires Saint-Luc’s pediatric hepato-gastroenterology division were enrolled retrospectively and prospectively; both datasets were merged. MTZ was administered over at least 14 days on top of standard treatment (ursodeoxycholic acid, azathioprine, and steroids). Fecal and blood samples were collected before (T0) and at MTZ day 14 (T14). Sustained biochemical remission was defined by the reduction of transaminases (AST and ALT), gamma-glutamyl transferase (GGT), and CRP until 12 months post-MTZ.

Results:

A total of 18 patients (mean age, 13.2 ± 4.5 years) were enrolled (13 ASC and 5 PSC), and divided in remission or relapse patients. CRP, AST, ALT, and GGT levels decreased post-MTZ in both groups (excepting GGT in relapse patients), with decreases between T0 and T14 being significant for AST and ALT. Relapse patients were older (P = 0.0351) and in late-disease stage, with mainly large-duct PSC (P = 0.0466). In remission patients, the mean plasma relative abundance of hydrophilic BA increased by +6.3% (P = 0.0391) after MTZ. Neither at baseline nor T14, there were significant differences in gut microbiota recorded.

Conclusion:

These data are likely indicative of long-term benefits following MTZ therapy at early-stage ASC or PSC, with increased hydrophilic BA abundance. Multicenter prospective studies are needed.
Unexpected Etiology of Intussusception in an Adolescent Patient
Authors: Alshareefy Yasir , Alshareefy Ali
Published: July 2023

Intussusception is a common cause of acute and subacute small bowel obstruction in children, young, and older patients; however, despite increasing awareness of the condition and the number of patients diagnosed with it across all ages, its clinical and diagnostic approach remains challenging. A 17-year-old girl attended our gastroenterology outpatient department complaining of a 6-month history of recurrent right iliac fossa pain associated with nausea and vomiting at times with no past medical history of note. Initial blood tests revealed a slightly raised CRP (9.1 mg/L) and a significantly elevated fecal calprotectin (>1000 µg/g). Computed axial tomography scan of the abdomen and pelvis revealed ileocecal intussusception with no evidence of small or large bowel obstruction. On subsequent colonoscopy a 5-cm mass protruding through the ileocecal valve was identified and multiple biopsies were taken for histological analysis, which confirmed a diagnosis of Burkitt’s lymphoma. The lesion was surgically resected and plans for adjuvant chemotherapy were discussed. The learning lessons to take from this case are to widen the list of differential diagnoses of unexplained recurrent abdominal pain to include intussusception and to actively rule it out with an appropriate diagnostic approach that addresses its potential malignant etiology across all ages.
Pediatric Nasoorbitoethmoid Fractures: A Single Institution’s 15-Year Experience
Authors: Glenney Anne E. , Irgebay Zhazira , Cheng Lucille G. , Comerci Alexander J. , Mocharnuk Joseph W. , Bruce Madeleine K. , Anstadt Erin E. , Saladino Richard A. , Dvoracek Lucas A. , Losee Joseph E. , Goldstein Jesse A.
Published: July 2023

Background:

Nasoorbitoethmoid (NOE) fractures impact growth of the craniofacial skeleton in children, which may necessitate differentiated management from adult injuries. This study describes characteristics, management, and outcomes of NOE fractures in children seen at a single institution.

Methods:

A retrospective review of patients under 18 years who presented to our institution from 2006 to 2021 with facial fractures was conducted; patients with NOE fractures were included. Data collected included demographics, mechanism of injury, fracture type, management, and outcomes.

Results:

Fifty-eight patients met inclusion criteria; 77.6% presented with Manson–Marcowitz Type I fractures, 17.2% with Type II, and 5.2% with Type III. The most common cause of injury was motor vehicle accidents (MVAs, 39.7%) and sports (31%). Glasgow Coma Scale and injury mechanism were not predictive of injury severity in the pediatric population (P=0.353, P=0.493). Orbital fractures were the most common associated fractures (n=55, 94.8%); parietal bone fractures were more likely in Type III fractures (P=0.047). LeFort III fractures were more likely in type II fractures (P=0.011). Soft tissue and neurological injuries were the most common associated injuries regardless of NOE fracture type (81% and 58.6%, respectively). There was no significant difference in type of operative management or in the rates of adverse outcomes between types of NOE fractures.

Conclusions:

These findings suggest that pediatric NOE fractures, although rare, present differently from adult NOE fractures and that revisiting predictive heuristics and treatment strategies is warranted in this population.
Older age bipolar disorder
Authors: Beunders Alexandra J.M. , Orhan Melis , Dols Annemiek
Published: July 2023

Purpose of review

Older age bipolar disorder (OABD) refers to patients with bipolar disorder aged 50 years and over. There is a paucity of evidence-based guidelines specific to OABD, but in recent years, several studies have been published on OABD. The current review synthesizes previous literature (up to January 1, 2021) as well as most recent literature on OABD (since January 1, 2021).

Recent findings

This review covers the following themes: diagnosis and specifiers, clinical course, psychosocial functioning, cognition, physical comorbidities, and pharmacotherapy. On the basis of the latest data, specific clinical recommendations are proposed for each theme.

OABD forms a more complex subgroup of bipolar disorder, with an increased risk of cognitive deficits, physical comorbidities, impaired psychosocial functioning, and premature death. The distinctions between BD-I and BD-II and between EOBD and LOBD do not clinically represent relevant subtypes for OABD patients. Mental healthcare professionals should treat all OABD patients with an integrative care model that takes into account cognitive and physical comorbidities and that contains elements aimed at improvement of psychosocial functioning and quality of life. Older age itself should not be a reason to withhold lithium treatment. Future research should collect data on essential data domains using validated measurement scales.
JMM Profile: West Nile virus
Authors: Sewgobind Sanam , McCracken Fiona , Schilling Mirjam
Published: July 2023

Graphical abstract

West Nile virus (WNV) is transmitted by mosquitoes in a mosquito-bird-mosquito enzootic cycle, with spillover infections in humans and horses. Created with BioRender.com.
Metagenomic comparisons reveal a highly diverse and unique viral community in a seasonally fluctuating hypersaline microbial mat
Authors: Cisneros-Martínez Alejandro Miguel , Eguiarte Luis E. , Souza Valeria
Published: July 2023

In spring 2016, a shallow hypersaline pond (50×25 m) was found in the Cuatro Cienegas Basin (CCB). This pond, known as Archaean Domes (AD) because of its elastic microbial mats that form dome-shaped structures due to the production of reducing gases reminiscent of the Archaean eon, such as methane and hydrogen sulfide, harbour a highly diverse microbial community, rich in halophilic and methanogenic archaea. AD is a seasonally fluctuating hypersaline site, with salinity ranging from low hypersaline (5.3%) during the wet season to high hypersaline (saturation) during the dry season. To characterize the viral community and to test whether it resembles those of other hypersaline sites (whose diversity is conditioned by salinity), or if it is similar to other CCB sites (with which it shares a common geological history), we generated 12 metagenomes from different seasons and depths over a 4 year period and compared them to 35 metagenomes from varied environments. Haloarchaeaviruses were detected, but were never dominant (average of 15.37 % of the total viral species), and the viral community structure and diversity were not affected by environmental fluctuations. In fact, unlike other viral communities at hypersaline sites, AD remained more diverse than other environments regardless of season. β-Diversity analyses show that AD is closely related to other CCB sites, although it has a unique viral community that forms a cluster of its own. The similarity of two surface samples to the 30 and 50 cm depth samples, as well as the observed increase in diversity at greater depths, supports the hypothesis that the diversity of CCB has evolved as a result of a long time environmental stability of a deep aquifer that functions as a ‘seed bank’ of great microbial diversity that is transported to the surface by sporadic groundwater upwelling events.
Removing direct photocurrent artifacts in optogenetic connectivity mapping data via constrained matrix factorization
Authors: Antin Benjamin , Sadahiro Masato , Gajowa Marta , Triplett Marcus A. , Adesnik Hillel , Paninski Liam
Published: July 2023

Monosynaptic connectivity mapping is crucial for building circuit-level models of neural computation. Two-photon optogenetic stimulation, when combined with whole-cell recordings, has the potential to map monosynaptic connectivity at an unprecedented scale. However, optogenetic mapping of nearby connections poses a challenge, due to stimulation artifacts. When the postsynaptic cell expresses opsin, optical excitation can directly induce current in the patched cell, confounding connectivity measurements. This problem is most severe in nearby cell pairs, where synaptic connectivity is often strongest. To overcome this problem, we developed a computational tool, Photocurrent Removal with Constraints (PhoRC). Our method is based on a constrained matrix factorization model which leverages the fact that photocurrent kinetics are consistent across repeated stimulations at similar laser power. We demonstrate on real and simulated data that PhoRC consistently removes photocurrents while preserving synaptic currents, despite variations in photocurrent kinetics across datasets. Our method allows the discovery of synaptic connections which would have been otherwise obscured by photocurrent artifacts, and may thus reveal a more complete picture of synaptic connectivity. PhoRC runs faster than real time and is available athttps://github.com/bantin/PhoRC.
Activity of natural occurring entomopathogenic fungi on nymphal and adult stage ofPhilaenus spumarius
Authors: Bodino N. , Barbera R. , Gonzalez-Mas N. , Demichelis S. , Bosco D. , Dolci P.
Published: July 2023

The spittlebugPhilaenus spumarius(Hemiptera: Aphrophoridae) is the predominant vector ofXylella fastidiosa(Xanthomonadales: Xanthomonadaceae) in Apulia and Europe. Current control strategies of the insect vector rely on mechanical management of nymphal stages and insecticide application against adult populations. Entomopathogenic fungi (EPF) are biological control agents naturally attacking spittlebugs and may effectively reduce population levels of host species. Different experimental trials in controlled conditions have been performed to i) identify naturally occurring EPF onP. spumariusin Northwestern Italy, and ii) evaluate the potential for biocontrol of the isolated strains on both nymphal and adult stages of the spittlebug. Four EPF species were isolated from deadP. spumariuscadavers collected in semi-field conditions:Beauveria bassiana, Conidiobolus coronatus, Fusarium equisetiandLecanicillium aphanocladii. All the fungal isolates showed entomopathogenic potential against nymphal stages ofP. spumarius(≈ 45 % mortality), except forF. equiseti, in preliminary trials. No induced mortality was observed on the adult stage.Lecanicillium aphanocladiiwas the most promising fungus and its pathogenicity against spittlebug nymphs was further tested in different formulations (conidia vs blastospores) and with natural adjuvants. Blastospore formulation was the most effective in killing nymphal instars and reducing the emergence rate ofP. spumariusadults, reaching mortality levels (90%) similar to those of the commercial product Naturalis®, while no or adverse effect of natural adjuvants was recorded. The encouraging results of this study pave the way for testing EPF isolates againstP. spumariusin field conditions and find new environmentally friendly control strategies against insect vectors ofX. fastidiosa.
Distinct Functional States of Neutrophils by Actin Disassembly and NF-kB/STAT3 Signaling
Authors: Heineken Niko , Schumacher Jan C. , Exner Tarik , Neuenfeldt Friederike S. , Habicht Jüri , Kahlich Franz , Platzer Hadrian , Merle Uta , Renkawitz Tobias , Samstag Yvonne , Grieshaber-Bouyer Ricardo , Autenrieth Stella , Wabnitz Guido
Published: July 2023

Polymorphonuclear neutrophils (PMNs) can differentiate into distinct states, which can either exacerbate or resolve inflammation. Our study shows that mice challenged with TLR agonists exhibited PMN differentiation along two major paths characterized by the expression of CCR5 or PD-L1. Similar differentiation was observed in the blood of severe COVID-19 patients and the synovial fluid of osteoarthritis patients. Prolongedin vitropriming of human PMNs modeled the differentiation paths. Actin disassembly favored CCR5 upregulation, while NF-kB activation stabilized the actin cytoskeleton and suppressed the development of CCR5+PMNs. Additionally, PD-L1 upregulation was triggered by STAT3 signaling and NF-kB activation. Functionally, CCR5 expressing PMNs were pro-NETotic, while PD-L1+PMNs showed immunosuppressive functions by inhibiting T cell proliferation via PD1. Together, PMN differentiation depended on the priming conditions, and the balance between actin disassembly and NF-kB/STAT3 activation translated the present micro-milieu into phenotypic and functional diversification of PMNs.

Synopsis

Neutrophils underwent phenotypical and functional diversification bothin vivoandin vitro. Actin disassembly led to the generation of CCR5highneutrophils with increased spontaneous NETosis, whereas NF-kB and STAT3 induced PD-L1 expression with T-cell suppressive properties as a deviation from the default pathway.

PMN of mice challenged with TLR agonists develop two distinct phenotypes, CCR5highand PD-L1high.

CCR5 and PD-L1-defined neutrophil phenotypes were found in blood of patients with severe COVID-19 and in the synovial fluid of osteoarthritis patients.

In vitropriming induced a similar bifurcation of PMN phenotypes marked by either CCR5 or PD-L1.

Actin disassembly preceded canonical development of CCR5+PMN.

NF-kB halted actin disassembly by LPL regulation.

During neutrophil priming, STAT3 aided NF-kB in the expression of PD-L1.

Graphical abstract
Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts
Authors: Trifault Barbara , Mamontova Victoria , Cossa Giacomo , Ganskih Sabina , Wei Yuanjie , Hofstetter Julia , Bhandare Pranjali , Baluapuri Apoorva , Solvie Daniel , Ade Carsten P. , Gallant Peter , Wolf Elmar , Munschauer Mathias , Burger Kaspar
Published: July 2023

RNA-binding proteins (RBPs) stimulate the DNA damage response (DDR). The RBP NONO marks nuclear paraspeckles in unperturbed cells and undergoes poorly understood re-localisation to the nucleolus upon induction of DNA double-strand breaks (DSBs). Here we show that treatment with the topoisomerase-II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-induced nucleolar antisense RNAs (diNARs) in human cells. diNARs originate from the nucleolar intergenic spacer and tether NONO to the nucleolus via its RRM1 domain. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signaling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.
Swimming by spinning: spinning-top type rotations regularize sperm swimming into persistently symmetric paths in 3D
Authors: Ren Xiaomeng , Bloomfield-Gadêlha Hermes
Published: July 2023

Sperm modulate their flagellar symmetry to navigate through complex physico-chemical environments and achieve reproductive function. Yet it remains elusive how sperm swim forwards despite the inherent asymmetry of several components that constitutes the flagellar engine. Despite the critical importance of symmetry, or the lack of it, on sperm navigation and its physiological state, there is no methodology to date that can robustly detect the symmetry state of the beat in free-swimming sperm in 3D. How does symmetric progressive swimming emerge even for asymmetric beating, and how can beating (a)symmetry be inferred experimentally? Here, we numerically resolve the fluid mechanics of swimming around asymmetrically beating spermatozoa. This reveals that sperm spinning critically regularizes swimming into persistently symmetric paths in 3D, allowing sperm to swim forwards despite any imperfections on the beat. The sperm orientation in three-dimensions, and not the swimming path, can inform the symmetry state of the beat, eliminating the need of tracking the flagellum in 3D. We report a surprising correspondence between the movement of sperm and spinning-top experiments, indicating that the flagellum drives “spinning-top” type rotations during sperm swimming, and that this parallel is not a mere analogy. These results may prove essential in future studies on the role of (a)symmetry in spinning and swimming microorganisms and micro-robots, as body orientation detection has been vastly overlooked in favour of swimming path detection. Altogether, sperm rotation may provide a foolproof mechanism for forward propulsion and navigation in nature that would otherwise not be possible for flagella with broken symmetry.
Using UAV-based temporal spectral indices to dissect changes in the stay green trait in wheat
Authors: Yu Rui , Cao Xiaofeng , Liu Jia , Nie Ruiqi , Zhang Chuanliang , Yuan Meng , Huang Yanchuan , Liu Xinzhe , Zheng Weijun , Wang Changfa , Wu Tingting , Su Baofeng , Kang Zhensheng , Zeng Qingdong , Han Dejun , Wu Jianhui
Published: July 2023

Stay green (SG) in wheat, a beneficial trait for increasing yield and stress resistance, needs to be supported by analysis of the underlying genetic basis. Spectral reflectance indices (SIs) provide non-destructive tools to evaluate crop temporal senescence. However, few SI-based SG quantification pipelines for analyzing diverse wheat panels in the field are available. Here, we first applied SIs to monitor the senescence dynamics of 565 diverse wheat accessions from anthesis to maturation stages during two field seasons. Based on over 12,000 SIs data set, four SIs (NDVI, GNDVI, NDRE and OSAVI) were selected to develop relative stay green scores (RSGS) and the senescence of wheat populations occurs mainly at four developmental stages stage 1 (S1) to S4, accounting for the final SG indicators. A RSGS-based genome-wide association study identified 47 high-confidence quantitative trait loci (QTL) harboring 3,079 SNPs significantly associated with RSGS and 1,085 corresponding candidate genes in the two seasons; 15 QTL overlapped or were adjacent to known SG-related QTL or genes and the remaining QTL were novel. Finally, we selected three superior candidate genes (TraesCS6B03G0356400,TraesCS2B03G1299500, andTraesCS2A03G1081100) as examples by transcriptomes, gene annotation, and gene-based association analysis for further analysis and found that utilization of superior SG-related variation in China gradually increased following the Green Revolution. The study provides a useful reference for further SG-related gene discovery of favorable variations in diverse wheat panels.
Long-Distance Electron Transport in Multicellular Freshwater Cable Bacteria
Authors: Yang Tingting , Chavez Marko S. , Niman Christina M. , Xu Shuai , El-Naggar Mohamed Y.
Published: July 2023

Filamentous multicellular cable bacteria perform centimeter-scale electron transport in a process that couples oxidation of an electron donor (sulfide) in deeper sediment to the reduction of an electron acceptor (oxygen or nitrate) near the surface. While this electric metabolism is prevalent in both marine and freshwater sediments, detailed electronic measurements of the conductivity previously focused on the marine cable bacteria (CandidatusElectrothrix), rather than freshwater cable bacteria, which form a separate genus (CandidatusElectronema) and contribute essential geochemical roles in freshwater sediments. Here, we characterize the electron transport characteristics ofCa.Electronema cable bacteria from Southern California freshwater sediments. Current-voltage measurements of intact cable filaments bridging interdigitated electrodes confirmed their persistent conductivity under a controlled atmosphere and the variable sensitivity of this conduction to air exposure. Electrostatic and conductive atomic force microscopies mapped out the characteristics of the cell envelope’s nanofiber network, implicating it as the conductive pathway in a manner consistent with previous findings in marine cable bacteria. Four-probe measurements of microelectrodes addressing intact cables demonstrated nanoampere currents up to 200 μm lengths at modest driving voltages, allowing us to quantify the nanofiber conductivity at 0.1 S/cm for freshwater cable bacteria filaments under our measurement conditions. Such a high conductivity can support the remarkable sulfide-to-oxygen electrical currents mediated by cable bacteria in sediments. These measurements expand the knowledgebase of long-distance electron transport to the freshwater niche while shedding light on underlying conductive network of cable bacteria.

Significance

Cable bacteria are multicellular filaments composed of up-to-thousands of end-to-end cells and are found worldwide in both marine and freshwater sediments. Remarkably, these cells gain energy from a long-distance electron transport process that carries electrons generated by sulfide oxidation in deeper sediment layers to drive oxygen reduction near the sediment-water interface. This electric metabolism requires an unusually high electronic conductivity, previously thought impossible in natural biological materials. However, the underlying mechanism(s) remain poorly understood, and previous characterization of the conductivity largely focused on marine cable bacteria. Here, we characterize and quantify the electronic conductivity of freshwater cable bacteria from sediments in Southern California, with emphasis on the role of the conductive periplasmic fiber network in routing electron transport along cables.
Tandemly duplicatedMYBgenes specifically in the Phaseoleae lineage are functionally diverged in the regulation of anthocyanin biosynthesis
Authors: Ma Ruirui , Huang Wenxuan , Hu Quan , Tian Guo , An Jie , Fang Ting , Liu Jia , Hou Jingjing , Zhao Meixia , Sun Lianjun
Published: July 2023

Gene duplications have long been recognized as a driving force in the evolution of genes, giving rise to novel functions. The soybean genome is characterized by a large extent of duplicated genes. However, the extent and mechanisms of functional divergence among these duplicated genes in soybean remain poorly understood. In this study, we revealed that tandem duplication ofMYBgenes, which occurred specifically in the Phaseoleae lineage, exhibited a stronger purifying selection in soybean compared to common bean. To gain insights into the diverse functions of theseMYBgenes in anthocyanin biosynthesis, we examined the expression, transcriptional activity, metabolite, and evolutionary history of fourMYBgenes (GmMYBA5,GmMYBA2, GmMYBA1andGlyma.09g235000), which were presumably generated by tandem duplication in soybean. Our data revealed thatGlyma.09g235000had become a pseudogene, while the remaining threeMYBgenes exhibited strong transcriptional activation activity and promoted anthocyanin biosynthesis in different soybean tissues. Furthermore,GmMYBA5produced distinct compounds inNicotiana benthamianaleaves compared toGmMYBA2andGmMYBA1due to variations in their DNA binding domains. The lower expression of anthocyanin related genes inGmMYBA5resulted in lower levels of anthocyanins compared toGmMYBA2andGmMYBA1. Metabolomics analysis further demonstrated the diverse and differential downstream metabolites, suggesting their functional divergence in metabolites following gene duplication. Together, our data provided evidence of functional divergence within theMYBgene cluster following tandem duplication, which shed light on the potential evolutionary direction of gene duplications during legume evolution.
The Patent and Literature Antibody Database (PLAbDab): an evolving reference set of functionally diverse, literature-annotated antibody sequences and structures
Authors: Abanades Brennan , Olsen Tobias H. , Raybould Matthew I. J. , Aguilar-Sanjuan Broncio , Wong Wing Ki , Georges Guy , Bujotzek Alexander , Deane Charlotte M.
Published: July 2023

Antibodies are key proteins of the adaptive immune system, and there exists a large body of academic literature and patents dedicated to their study and concomitant conversion into therapeutics, diagnostics, or reagents. These documents often contain extensive functional characterisations of the sets of antibodies the describe. However, leveraging these heterogeneous reports, for example to offer insights into the properties of query antibodies of interest, is currently challenging as there is no central repository through which this wide corpus can be mined by sequence or structure.

Here, we present PLAbDab (the Patent and Literature Antibody Database), a self-updating repository containing over 150,000 paired antibody sequences and 3D structural models, of which over 65,000 are unique. Each entry in the database also contains the title and authors of its literature source. Here we describe the methods used to extract, filter, pair, and model the antibodies in PLAbDab, and showcase how PLAbDab can be searched by sequence, structure, or keyword.

PLAbDab uses include annotating query antibodies with potential antigen information from similar entries, analysing structural models of existing antibodies to identify modifications that could improve their properties, and compiling bespoke datasets of antibody sequences/structures known to bind to a specific antigen. PLAbDab is freely available via Github (https://github.com/oxpig/PLAbDab) and as a searchable webserver (https://opig.stats.ox.ac.uk/webapps/plabdab/).