bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotic Interactions
Authors: Taiz Lincoln , Zeiger Eduardo , Møller Ian Max , Murphy Angus
Published: September 2023

This chapter addresses biotic interactions, starting with examples of beneficial associations between plants and microorganisms. Such mutually beneficial biotic interactions are termed mutualisms. The chapter then considers various types of harmful interactions between plants, herbivores, and pathogens and the defensive mechanisms used by plants against them. It surveys the wide range of constitutive and inducible defenses that plants deploy to fend off insect herbivores. Constitutive defenses are always present, whereas inducible defenses are triggered in response to attack. Unlike constitutive defenses, inducible defenses require specific detection systems and signal transduction pathways that can sense the presence of an herbivore or pathogen and alter gene expression and metabolism accordingly. Finally, the chapter notes the important roles that volatile organic compounds play in repelling herbivores, attracting insect predators, and acting as distress signals between different parts of plants and between neighboring plants.
Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants
Authors: Zlatic Stephanie A , Werner Erica , Surapaneni Veda , Lee Chelsea E , Gokhale Avanti , Singleton Kaela , Duong Duc , Crocker Amanda , Gentile Karen , Middleton Frank , Dalloul Joseph Martin , Liu William Li-Yun , Patgiri Anupam , Tarquinio Daniel , Carpenter Randall , Faundez Victor
Published: September 2023

Genes mutated in monogenic neurodevelopmental disorders are broadly expressed. This observation supports the concept that monogenic neurodevelopmental disorders are systemic diseases that profoundly impact neurodevelopment. We tested the systemic disease model focusing on Rett syndrome, which is caused by mutations in MECP2. Transcriptomes and proteomes of organs and brain regions from Mecp2-null mice as well as diverse MECP2-null male and female human cells were assessed. Widespread changes in the steady-state transcriptome and proteome were identified in brain regions and organs of presymptomatic Mecp2-null male mice as well as mutant human cell lines. The extent of these transcriptome and proteome modifications was similar in cortex, liver, kidney, and skeletal muscle and more pronounced than in the hippocampus and striatum. In particular, Mecp2- and MECP2-sensitive proteomes were enriched in synaptic and metabolic annotated gene products, the latter encompassing lipid metabolism and mitochondrial pathways. MECP2 mutations altered pyruvate-dependent mitochondrial respiration while maintaining the capacity to use glutamine as a mitochondrial carbon source. We conclude that mutations in Mecp2/MECP2 perturb lipid and mitochondrial metabolism systemically limiting cellular flexibility to utilize mitochondrial fuels.
The clinical-histologic and prognostic characteristics in patients with a second primary non-small-cell lung cancer after a lobectomy
Authors: Wu Lei-Lei , Wang Rang-Rang , Qian Jia-Yi , Liu Yu’e , Ma Shang-Shang , Li Ming-Jun , Xie Long-Yan , Li Zhi-Xin , Li Kun , Sheng Bing-Yong , Ding Jun-Rong , Xie Dong
Published: September 2023

OBJECTIVES

The goal of this study was to investigate whether an operation can offer survival benefits for patients with a second primary non-small-cell lung cancer (NSCLC) after a lobectomy for a first primary NSCLC and to analyse the characteristics affecting the survival of those patients.

METHODS

We performed survival analyses of patients with a second primary NSCLC based on the Surveillance, Epidemiology and End Results program and used propensity score matching to reduce the potential bias and analyse the data. In addition, the primary observational end point was overall survival (OS), and the secondary observational end point was histologic migration.

RESULTS

The data from 944 patients were used to perform the main analysis. A total of 36.2% of patients experienced a shift in tumour histologic type between 2 diagnoses of primary NSCLC, and this shift significantly affected OS (P = 0.0065). The median survival time in patients with surgical resection and those without an operation was 52.0 months versus 33.0 months, respectively. Patients with surgical resection at the secondary diagnosis had better survival than those without surgery (5-year OS rate: 48.0% vs 34.0%, P < 0.001). In addition, compared with a pneumonectomy and a sublobar resection, a lobectomy was the optimal surgical procedure for patients diagnosed with a second primary NSCLC after adjusting for other confounders (adjusted hazard ratio: 0.68, P < 0.01). However, in the subgroup analysis, lobar and sublobar resections could provide similar survival benefits for patients with tumour size ≤20 mm (P = 0.5).

CONCLUSIONS

The operation, especially a lobectomy, can prolong OS in patients with a second primary NSCLC. Besides, sublobar resection can be performed in selected patients with tumour size ≤20 mm. Moreover, histologic migration may impact the survival of those patients with a secondary primary NSCLC.
Is the Positive Effect of Education on Ethnic Tolerance a Method Artifact? A Multifactorial Survey Experiment on Social Desirability Bias in Sweden
Authors: Adman Per , Gschwind Lutz
Published: September 2023

Educated individuals are believed to be more tolerant towards ethnic minorities—a finding widely inferred from standard survey items. We propose a new approach that helps mitigate the risk of socially desirability bias (SDB), using a multifactorial survey experiment with name-based vignette dimensions. The experiment is strategically inserted into a question about a social dilemma not related to ethnicity. By embedding our experiment into an established survey—the Swedish part of the European Values Survey—we show that individuals with a high level of education are more tolerant towards ethnic minorities, even under a lower risk of SDB. The study strengthens findings in prior research and supports the hypothesis that education can further ethnic tolerance.
Nirmatrelvir/Ritonavir Use and Hospitalizations or Death in a Previously Uninfected Nonhospitalized High-Risk Population With COVID-19: A Matched Cohort Study
Authors: Butt Adeel A , Yan Peng , Shaikh Obaid S , Talisa Victor B , Omer Saad B , Mayr Florian B
Published: September 2023

Objective

To determine the association of nirmatrelvir/ritonavir (NMV/r) with hospitalization or death within 30 days as compared with untreated controls previously uninfected and nonhospitalized.

Methods

We used a matched cohort design using inverse probability of treatment weight (IPTW). Individuals prescribed NMV/r within 3 days of COVID-19 diagnosis were compared with IPTW-based untreated controls. Variables for IPTW included age, race, sex, body mass index, geographic location, vaccination status, and multiple comorbidities. Additional analyses were conducted on NMV/r-treated and propensity score–matched untreated controls.

Results

Among 7615 individuals prescribed NMV/r and 62 077 controls identified between 1 January 2022 and 25 February 2023, the risk of hospitalization/death was lower among NMV/r-treated persons vs untreated controls (243 vs 3468 events; absolute risk difference [ARD], −2.36 [95% CI, −2.57 to −2.14]). The difference was significant for those >60 and ≤60 years old (ARD, −3.86 [95% CI, −4.19 to −3.54] vs −0.27 [95% CI, −0.51 to −0.03]) and for persons asymptomatic and symptomatic (ARD, −7.09 [95% CI, −7.62 to −6.55] vs −1.46 [95% CI, −1.66 to −1.25]). Significant benefit was observed among individuals unvaccinated and vaccinated, with or without a booster dose.

Conclusions

NMV/r is associated with a significant reduction in 30-day hospitalization or death among individuals previously uninfected and nonhospitalized.
Risk of Malaria Following Untreated Subpatent Plasmodium falciparum Infections: Results Over 4 Years From a Cohort in a High-Transmission Area in Western Kenya
Authors: Zeno Erica E , Obala Andrew A , Pence Brian , Freedman Elizabeth , Mangeni Judith N , Lin Jessica T , Abel Lucy , Edwards Jessie K , Gower Emily W , Taylor Steve M
Published: September 2023

Background

People with suspected malaria may harbor Plasmodium falciparum undetected by rapid diagnostic test (RDT). The impact of these subpatent infections on the risk of developing clinical malaria is not fully understood.

Methods

We analyzed subpatent P. falciparum infections using a longitudinal cohort in a high-transmission site in Kenya. Weighted Kaplan-Meier models estimated the risk difference (RD) for clinical malaria during the 60 days following a symptomatic subpatent infection. Stratum-specific estimates by age and transmission season assessed modification.

Results

Over 54 months, we observed 1128 symptomatic RDT-negative suspected malaria episodes, of which 400 (35.5%) harbored subpatent P. falciparum. Overall, the 60-day risk of developing clinical malaria was low following all episodes (8.6% [95% confidence interval, 6.7%–10.4%]). In the low-transmission season, the risk of clinical malaria was slightly higher in those with subpatent infection, whereas the opposite was true in the high-transmission season (low-transmission season RD, 2.3% [95% confidence interval, .4%–4.2%]; high-transmission season RD, −4.8% [−9.5% to −.05%]).

Conclusions

The risk of developing clinical malaria among people with undetected subpatent infections is low. A slightly elevated risk in the low-transmission season may merit alternate management, but RDTs identify clinically relevant infections in the high-transmission season.
Immune cells in skin inflammation, wound healing, and skin cancer
Authors: Zhang Yuhan , Lu Qianjin
Published: September 2023

Given the self-evident importance of cutaneous immunity in the maintenance of body-surface homeostasis, disturbance of the steady-state skin is inextricably intertwined with dysfunction in cutaneous immunity. It is often overlooked by people that skin, well-known as a solid physical barrier, is also a strong immunological barrier, considering the abundant presence of immune cells including lymphocytes, granulocytes, dendritic cells, and macrophages. What's more, humoral immune components including cytokines, immunoglobulins, and antimicrobial peptides are also rich in the skin. This review centers on skin inflammation (acute and chronic, infection and aseptic inflammation), wound healing, and skin cancer to elucidate the elaborate network of immune cells in skin diseases.
Impact of state telehealth policies on telehealth use among patients with newly diagnosed cancer
Authors: Yen Tina W F , Pan I-Wen , Shih Ya-Chen Tina
Published: September 2023

Background

Telehealth restrictions were relaxed under the COVID-19 public health emergency. We examined telehealth use before and during the pandemic among patients with newly diagnosed cancers and the association between state policies and telehealth use.

Methods

The study cohort was constructed from Optum’s deidentified Clinformatics Data Mart and included patients with lymphoma, female breast cancer, colorectal cancer, prostate cancer, and lung cancer diagnosed between March 1, 2019, and March 31, 2021. We performed an interrupted time series analysis to examine the trend of cancer-related telehealth use within 1 month of diagnosis relative to the timing of the COVID-19 public health emergency and multivariable logistic regressions to examine factors—specifically, state parity laws and regulations on cross-state practice—associated with telehealth.

Results

Of 110 461 patients, the rate of telehealth use peaked at 33.4% in April 2020, then decreased to 12% to 15% between September 2020 and March 2021. Among the 53 982 patients diagnosed since March 2020, telehealth use was statistically significantly lower for privately insured patients residing in states with coverage-only parity or no or unspecified parity than those in states with coverage and payment parity (adjusted rate = 20.2%, 19.1%, and 23.3%, respectively). The adjusted rate was lower for patients in states with cross-state telehealth policy limitations than for those in states without restrictions (14.9% vs 17.8%).

Conclusions

Telehealth use by patients diagnosed with cancer during the pandemic was higher among those living in states with more generous parity and less restrictive rules for cross-state practice. Policy makers contemplating whether to permanently relax certain telehealth policies must consider the impact on vulnerable patient populations who can benefit from telehealth.
Equitable representation on international benches and the appointment of tribunal members in investor–State dispute settlement: a historical perspective
Authors: Zhang Yanwen
Published: September 2023

The lack of diversity in the appointment of tribunal members in investment arbitration has long been subject to criticism. This article analyses the design of adjudicator appointment mechanisms and challenges the mainstream view that investment arbitration is modelled after the structures and procedures of commercial arbitration. Instead, drafters of the Convention on the Settlement of Investment Disputes Between States and Nationals of Other States (ICSID Convention) largely drew inspiration from the Permanent Court of Arbitration and the International Court of Justice. Following this institutional pedigree, the development of the equitable representation requirement is linked to the growing appreciation of the public aspects of the international judicial function. Nevertheless, drafters adopted Article 14(2) of the ICSID Convention mainly to facilitate the performance of the private function of dispute resolution. Through the historical lens, controversies surrounding different approaches for addressing diversity concerns in the ongoing investor–State dispute settlement reform are essentially surface products of deeper disagreements on the private and public aspects of the judicial function.
Monte Carlo goodness-of-fit tests for degree corrected and related stochastic blockmodels
Authors: Karwa Vishesh , Pati Debdeep , Petrović Sonja , Solus Liam , Alexeev Nikita , Raič Mateja , Wilburne Dane , Williams Robert , Yan Bowei
Published: September 2023

We construct Bayesian and frequentist finite-sample goodness-of-fit tests for three different variants of the stochastic blockmodel for network data. Since all of the stochastic blockmodel variants are log-linear in form when block assignments are known, the tests for the latent block model versions combine a block membership estimator with the algebraic statistics machinery for testing goodness-of-fit in log-linear models. We describe Markov bases and marginal polytopes of the variants of the stochastic blockmodel and discuss how both facilitate the development of goodness-of-fit tests and understanding of model behaviour. The general testing methodology developed here extends to any finite mixture of log-linear models on discrete data, and as such is the first application of the algebraic statistics machinery for latent-variable models.
Assessing the neuroprotective efficacy of atorvastatin in traumatic brain injury: a systematic review protocol
Authors: Mugenyi Nathan , Sakaiwa Neontle , Darko Kwadwo , Shituluka Musakanya , Tango Tamara , Tunde Olobatoke , Lordstrong Akano , Saeed Ali Awadallah , Kamabu Larrey Kasereka , Mduma Emmanuel , Kyaruzi Victor , Shimber Emnet , Azouz Heba , Gankpe Fortune , Esene Ignatius , Tirsit Abenezer
Published: September 2023

Traumatic brain injury (TBI) is a significant public health threat, with an estimated 5.3 million people in the United States alone living with a disability related to TBI (1). The most common therapies for individuals with TBI at this time include supportive measures, direct monitoring and surgical interventions, but the treatment outcomes following TBI are still poor. Atorvastatin is one of 3-hydroxy–3-methylglutaryl coenzyme A reductase inhibitors commonly used for treatment reduction of low-density lipoprotein and relief of symptoms in cerebrovascular diseases, however, the recent randomized trials in animal models and human subjects have revealed a promising therapeutic effect for its use in the treatment of TBI that has shown a significant alleviation of neurological dysfunctions. Hence, this systematic review will streamline and provide a comprehensive avenue for understanding more about the dynamics of atorvastatin and its neuroprotective efficacy for the treatment of the severity of TBI and the improvement of functional outcomes. This systematic review will follow the 2020 PRISMA guidelines. Information sources will be obtained from electronic databases such as Pubmed, Cochrane Library, EMBASE and SCOPUS. All patients with TBI that received Atorvastatin will be included. The review will also include original peer-reviewed research articles addressing the efficacy of Atorvastatin in TBI in English. Ethical approval will not be required as there will be no human participant involvement in this study. The findings from this study will be disseminated at scientific conferences and published in a reputable peer-reviewed journal.

Strengths A wide range of study types will be included increasing the pool of information.Accuracy will be upheld as two to three reviewers will independently screen titles, abstracts and full texts.

Limitations Only studies in English will be included, hence studies in other languages that may be very informative will be excluded.
Spatially and temporally distinct Ca2+ changes in Lotus japonicus roots orient fungal-triggered signalling pathways towards symbiosis or immunity
Authors: Binci Filippo , Offer Elisabetta , Crosino Andrea , Sciascia Ivan , Kleine-Vehn Jürgen , Genre Andrea , Giovannetti Marco , Navazio Lorella
Published: September 2023

Plants activate an immune or symbiotic response depending on the detection of distinct signals from root-interacting microbes. Both signalling cascades involve Ca2+ as a central mediator of early signal transduction. In this study, we combined aequorin- and cameleon-based methods to dissect the changes in cytosolic and nuclear Ca2+ concentration caused by different chitin-derived fungal elicitors in Lotus japonicus roots. Our quantitative analyses highlighted the dual character of the evoked Ca2+ responses taking advantage of the comparison between different genetic backgrounds: an initial Ca2+ influx, dependent on the LysM receptor CERK6 and independent of the common symbiotic signalling pathway (CSSP), is followed by a second CSSP-dependent and CERK6-independent phase, that corresponds to the well-known perinuclear/nuclear Ca2+ spiking. We show that the expression of immunity marker genes correlates with the amplitude of the first Ca2+ change, depends on elicitor concentration, and is controlled by Ca2+ storage in the vacuole. Our findings provide an insight into the Ca2+-mediated signalling mechanisms discriminating plant immunity- and symbiosis-related pathways in the context of their simultaneous activation by single fungal elicitors.
A novel pectin methylesterase inhibitor, PMEI3, in common bean suggests a key role of pectin methylesterification in Pseudomonas resistance
Authors: De la Rubia Alfonso G , Largo-Gosens Asier , Yusta Ricardo , Sepúlveda-Orellana Pablo , Riveros Aníbal , Centeno María Luz , Sanhueza Dayan , Meneses Claudio , Saez-Aguayo Susana , García-Angulo Penélope
Published: September 2023

The mechanisms underlying susceptibility to and defense against Pseudomonas syringae (Pph) of the common bean (Phaseolus vulgaris) have not yet been clarified. To investigate these, 15-day-old plants of the variety Riñón were infected with Pph and the transcriptomic changes at 2 h and 9 h post-infection were analysed. RNA-seq analysis showed an up-regulation of genes involved in defense/signaling at 2 h, most of them being down-regulated at 9 h, suggesting that Pph inhibits the transcriptomic reprogramming of the plant. This trend was also observed in the modulation of 101 cell wall-related genes. Cell wall composition changes at early stages of Pph infection were associated with homogalacturonan methylation and the formation of egg boxes. Among the cell wall genes modulated, a pectin methylesterase inhibitor 3 (PvPMEI3) gene, closely related to AtPMEI3, was detected. PvPMEI3 protein was located in the apoplast and its pectin methylesterase inhibitory activity was demonstrated. PvPMEI3 seems to be a good candidate to play a key role in Pph infection, which was supported by analysis of an Arabidopsis pmei3 mutant, which showed susceptibility to Pph, in contrast to resistant Arabidopsis Col-0 plants. These results indicate a key role of the degree of pectin methylesterification in host resistance to Pph during the first steps of the attack.
Improved photosynthetic performance under unilateral weak light conditions in a wide–narrow-row intercropping system is associated with altered sugar transport
Authors: Chen Guopeng , Liu Ming , Zhao Xuyang , Bawa George , Liang Bing , Feng Liang , Pu Tian , Yong Taiwen , Liu Weiguo , Liu Jiang , Du Junbo , Yang Feng , Wu Yushan , Liu Chunyan , Wang Xiaochun , Yang Wenyu
Published: September 2023

Intercropping improves resource utilization. Under wide–narrow-row maize (Zea mays) intercropping, maize plants are subjected to weak unilateral illumination and exhibit high photosynthetic performance. However, the mechanism regulating photosynthesis under unilateral weak light remains unknown. We investigated the relationship between photosynthesis and sugar metabolism in maize under unilateral weak light. Our results showed that the net photosynthetic rate (Pn) of unshaded leaves increased as the level of shade on the other side increased. On the contrary, the concentration of sucrose and starch and the number of starch granules in the unshaded leaves decreased with increased shading due to the transfer of abundant C into the grains. However, sink loss with ear removal reduced the Pn of unshaded leaves. Intense unilateral shade (40% to 20% normal light), but not mild unilateral shade (60% normal light), reduced grain yield (37.6% to 54.4%, respectively). We further found that in unshaded leaves, Agpsl, Bmy, and Mexl-like expression significantly influenced sucrose and starch metabolism, while Sweet13a and Sut1 expression was crucial for sugar export. In shaded leaves, expression of Sps1, Agpsl, and Sweet13c was crucial for sugar metabolism and export. This study confirmed that unshaded leaves transported photosynthates to the ear, leading to a decrease in sugar concentration. The improvement of photosynthetic performance was associated with altered sugar transport. We propose a narrow-row spacing of 40 cm, which provides appropriate unilateral shade and limits yield reduction.
The role of branched-chain aminotransferase 1 in driving glioblastoma cell proliferation and invasion varies with tumor subtype
Authors: Fala Maria , Ros Susana , Sawle Ashley , Rao Jyotsna U , Tsyben Anastasia , Tronci Laura , Frezza Christian , Mair Richard , Brindle Kevin M
Published: September 2023

Background

Branched-chain aminotransferase 1 (BCAT1) has been proposed to drive proliferation and invasion of isocitrate dehydrogenase (IDH) wild-type glioblastoma cells. However, the Cancer Genome Atlas (TCGA) dataset shows considerable variation in the expression of this enzyme in glioblastoma. The aim of this study was to determine the role of BCAT1 in driving the proliferation and invasion of glioblastoma cells and xenografts that have widely differing levels of BCAT1 expression and the mechanism responsible.

Methods

The activity of BCAT1 was modulated in IDH wild-type patient-derived glioblastoma cell lines, and in orthotopically implanted tumors derived from these cells, to examine the effects of BCAT1 expression on tumor phenotype.

Results

In cells with constitutively high BCAT1 expression and a glycolytic metabolic phenotype, inducible shRNA knockdown of the enzyme resulted in reduced proliferation and invasion by increasing the concentration of α-ketoglutarate, leading to reduced DNA methylation, HIF-1α destabilization, and reduced expression of the transcription factor Forkhead box protein M1 (FOXM1). Conversely, overexpression of the enzyme increased HIF-1α expression and promoted proliferation and invasion. However, in cells with an oxidative phenotype and very low constitutive expression of BCAT1 increased expression of the enzyme had no effect on invasion and reduced cell proliferation. This occurred despite an increase in HIF-1α levels and could be explained by decreased TCA cycle flux.

Conclusions

There is a wide variation in BCAT1 expression in glioblastoma and its role in proliferation and invasion is dependent on tumor subtype.
The Market Inside the Market: Odd-Lot Quotes
Authors: Bartlett Robert P , McCrary Justin , O’Hara Maureen
Published: September 2023

We show current market practices relating to odd-lot quotes create a large “inside” market where better prices routinely exist relative to the National Best Bid or Offer. We show that odd-lot quotes play a price discovery role, and these quotes provide valuable information to traders with access to proprietary data feeds. Using a XGBoost machine learning algorithm that uses odd-lot data to predict future prices, we demonstrate a simple and profitable trading strategy. We argue the SEC’s proposed round-lot redefinition reduces—but does not eliminate—the high incidence of superior odd-lot quotes within the NBBO.
Risk Factors for Self-Harm Ideation Among Persons Treated With Opioids for Chronic Low Back Pain
Authors: Jamison Robert N. , Edwards Robert R. , Brown Roger , Barrett Bruce P. , Burzinski Cindy A. , Lennon Robert P. , Nakamura Yoshio , Schiefelbein Tony , Garland Eric L. , Zgierska Aleksandra E.
Published: September 2023

Objectives:

Chronic pain is a significant health concern that adversely affects all aspects of life, including emotional well-being. Opioids are prescribed for the management of refractory, severe chronic pain although they have been associated with adverse effects, including addiction and overdose. The aim of this study was to examine factors that predict thoughts of self-harm among adults with chronic pain who are prescribed opioids.

Methods:

Seven hundred sixty-five (N=765) persons with opioid-treated chronic lower back pain completed the Current Opioid Misuse Measure (COMM) and other validated questionnaires as part of a larger study. Response to one question from the COMM (“How often have you seriously thought about hurting yourself?”) was used to assess suicide risk on a 5-point scale (0=Never; 4=Very Often).

Results:

Participants were categorized into 3 groups according to their responses on the self-harm question: Never (N=628; 82.1%), Seldom or Sometimes (N=74; 9.7%) and Often or Very Often (N=63; 8.2%). Multivariate adjusted odds ratio (aOR) analyses indicated that reports of alcohol or drug overuse within the past month (aOR=1.41,[95% conf interval 1.11-1.78]), post-traumatic stress (PTSD; aOR=1.24,[1.07-1.44]), pain catastrophizing (aOR=1.03,[1.01-1.05]), not loving oneself (aOR=0.99,[.98-1.00]) and poor perceived mental health (aOR=0.94,[.92-.97]) were most associated with thoughts of self-harm. Importantly, ideation frequency of self-harm was highest among individuals treated with higher daily doses of opioids.

Discussion:

These results support the need for continued monitoring of adults treated with opioids for chronic pain, particularly among those on high-dose opioids who present with increased negative affect and concerns of substance misuse.
Preventing the Slide in High-Energy Intertrochanteric Fractures With Intramedullary Nails
Authors: Chan Daniel S. , Moghadamian Eric S.
Published: September 2023

Intramedullary nailing is the gold standard treatment for high-energy intertrochanteric femur fractures. Despite being associated with higher union and lower complication rates, it is not uncommon to see the proximal head and neck fragment “slide” and result in a shortened femoral neck and/or prominent cephalomedullary screws laterally. This type of subsidence in alignment can ultimately lead to suboptimal patient outcomes. In an effort to reduce this effect, surgeons should be able to identify preventable factors, as well as incorporate novel surgical techniques, to reduce the potential for malreduction and consequential “slide.”

Level of Evidence:

Therapeutic Level V.
Surgical prophylaxis in pediatric orthopedic patients with penicillin allergy: a multicentered retrospective prognostic study
Authors: Khokhar Ahmed S. , Batko Brian D. , Hanna Gabriel , Cleary Courtney , Rousseau Morgan , Crawford Lindsay , Edobor-Osula Folorunsho
Published: September 2023

Up to 20% of orthopedic surgeons still avoid the use of cephalosporins in patients with penicillin allergies despite its reported safety in the adult and general surgery pediatric population. The primary objective is to determine the incidence of adverse effects and allergic reactions when using cephalosporins in pediatric orthopedic patients labeled as penicillin-allergic as compared to those without previously reported penicillin allergy. A multicenter retrospective chart review was performed across three level 1 trauma centers from January 2013 to February 2020 to identify penicillin-allergic as well as non-penicillin-allergic pediatric patients treated for orthopedic injuries. Data were collected regarding patient demographics, antibiotic administered, timing of antibiotic administration, reported drug allergy, and described allergic reaction. Postoperative or intraoperative allergic reactions to antibiotics, surgical site infections, and complications were recorded. A total of 2289 surgeries performed by four fellowship-trained surgeons were evaluated. Eighty-five patients diagnosed with penicillin allergy were identified and underwent 95 surgeries and 95 patients without previously reported penicillin allergy underwent 95 surgeries. One patient, with a documented history of anaphylaxis to cefazolin, sustained an anaphylactic reaction intraoperatively to cefazolin. There were no other reported reactions, surgical site infections, or complications. There was no statistically significant difference in rate of allergic reaction in patients with previously reported penicillin allergy treated with cefazolin and those with no previous reported reaction (P > 0.05). Prophylaxis with cephalosporins is not associated with increased risk for allergic reaction. Cephalosporins can be safely administered to pediatric patients with penicillin allergy undergoing orthopedic intervention. Level of evidence: Level II, Multicenter Retrospective Prognostic Study.
‘Immunization during ART and ATI for HIV-1 vaccine discovery/development’
Authors: Stamatatos Leonidas
Published: September 2023

Purpose of review

Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that promote and guide the full maturation of broadly neutralizing antibody responses.

Recent findings

The HIV-1 envelope glycoprotein (Env) does not efficiently engage the germline precursors of broadly neutralizing antibodies (bnAbs). However, Env-derived proteins specifically designed to precisely do that, have been recently developed. These ‘germline-targeting’ Env immunogens activate naïve B cells that express the germline precursors of bnAbs but by themselves cannot guide their maturation towards their broadly neutralizing forms. This requires sequential immunizations with heterologous sets of Envs. These ‘booster’ Envs are currently unknown.

Combining germline-targeting Env immunization approaches during ART with ATI could lead to the identification of natural Envs that are responsible for the maturation of broadly neutralizing antibody responses during infection. Such Envs could then serve as booster immunogens to guide the maturation of glBCRs that have become activated by germline-targeting immunogens in uninfected subjects.
Effect of Double Povidone-Iodine Wash on Rate of Positive Donor Corneoscleral Rim Cultures: A 7-Year Eye Bank Analysis
Authors: Tran Tu M. , Fraser Daniel , Gillmor Christina L. , Roberts Edwin , Dahl Patricia , Meduri Alessandro , Kaufman Stephen C.
Published: September 2023

Introduction:

Starting October 2018, the Eye Bank Association of America modified the national standard protocol to incorporate a double povidone-iodine (P-I) wash at the time of procurement.

Purpose:

To determine if double P-I wash resulted in a reduced rate of positive donor rim cultures.

Methods:

A comprehensive database review was performed on consecutive corneoscleral tissue handled by The Eye-Bank for Sight Restoration (New York, NY) from January 2015 to December 2021. The primary outcome was the rate of positive corneoscleral rim cultures for bacteria or fungus. Secondary outcomes included rate of postoperative infection (eg, keratitis or endophthalmitis). For analysis, statistical significance was determined as P < 0.05.

Results:

Of 6079 corneal transplants performed, 3491 were done before implementation of double P-I wash with a total culture positive rate of 0.43%. There were 2588 corneal transplants performed after implementation of double P-I wash with a total positive culture rate of 0.23%, which is a significant reduction (Poisson regression incidence rate ratio [IRR] 0.35 [95% CI 0.089–0.61], P = 0.007). The most common organisms preimplementation were Candida species (46.7% of culture-positive rims), whereas no candida species were isolated postimplementation (logit regression, P = 0.034). Cutibacterium acnes culture positivity rate increased postimplementation to 50.0% versus 13.3% preimplementation (logit regression, P = 0.116). The rate of postoperative infection was 1.55% and 1.00% for preimplementation and postimplementation, respectively (IRR 0.30 [95% CI, 0.18–0.50], P < 0.001).

Conclusions:

The use of double P-I wash was associated with a decrease in the rate of positive corneoscleral donor rim cultures and a decrease in the rate of postoperative infection.
Clinical and Optical Coherence Tomography Correlation of Recurrence Patterns After Femtosecond Laser–Assisted Anterior Lamellar Keratoplasty in Reis–Bucklers Corneal Dystrophy
Authors: Chaurasia Sunita , Mishra Dilip K. , Murthy Somasheila , Das Rajashree , Edward Deepak P. , Ramappa Muralidhar
Published: September 2023

Purpose:

The aim of this study was to report the clinical profile and patterns of recurrence after femtosecond laser–assisted anterior lamellar keratoplasty (FALK) in Reis–Bucklers corneal dystrophy.

Methods:

This is a case series of 5 eyes of 4 patients with Reis–Bucklers corneal dystrophy. Clinical images of recurrence were correlated with the high-resolution optical coherence tomography. Histopathologic examination of excised corneal samples was performed when possible.

Results:

The median time to recurrence was 2 (1–5) years after FALK. Of the 5 eyes, 1 eye had primary FALK, whereas 4 eyes had secondary interventions, which included previous phototherapeutic keratectomy (once in 1 eye and twice in 2 eyes), and previous penetrating keratoplasty, followed by phototherapeutic keratectomy (1 eye). Recurrence was noted at the level of the subepithelium. In addition, 1 eye showed interface deposits along with epithelial downgrowth at the graft–host bed.

Conclusions:

The 2 distinct patterns of recurrence noted were at the subepithelial region and the interface. The clinical patterns of recurrence favor an epithelial origin of recurrent deposits.
simmr: An open-source tool to perform simulations in Mendelian Randomization
Authors: Lorincz-Comi Noah , Yang Yihe , Zhu Xiaofeng
Published: September 2023

Mendelian Randomization (MR) has become a popular tool for inferring causality of risk factors on disease. There are currently over 45 different methods available to perform MR, reflecting this extremely active research area. It would be desirable to have a standard simulation environment to objectively evaluate the existing and future methods. We presentsimmr, an open-source software for performing simulations to evaluate the performance of MR methods in a range of scenarios encountered in practice. Researchers can directly modify thesimmrsource code so that the research community may arrive at a widely accepted frame-work for researchers to evaluate the performance of different MR methods.
2-bromo-2’5’-dihydroxychalcone analogue Inhibits Endothelial Migration by Targeting VEGF-induced ERK 1/2 Phosphorylation
Authors: Hussain Aamir , Festa Joseph , Singh Harprit
Published: September 2023

Angiogenesis, the process of new blood vessel formation, is characterized by three essential hallmarks: endothelial proliferation, migration, and differentiation. Each is integral in angiogenesis related diseases, especially cancer. With drug efficacy stagnated due to acquired drug resistance and off target side effects, the need for combinatorial therapy is ever more present. To identify new compounds that could aid current antiangiogenic therapies, we report the preliminary mechanistic evaluation of a 2-bromo-2’5’-dihydroxychalcone analogue and its antimigratory effects on endothelial cells. After the synthesis and validation of the 2-bromo-2’5’-dihydroxychalcone analogue (AH9), its effect was tested in vitro using human umbilical vein endothelial cells (HUVEC). Initial investigations into 2-bromo-2’5’-dihydroxychalcone effect in vitro was conducted with a cell proliferation assay including MTT, afterward endothelial migration was measured with the scratch assay in subsequent functional studies. For mechanistic evaluation, vascular endothelial growth factor (VEGF) induced ERK phosphorylation using western blot was implemented. AH9 inhibited VEGF-induced ERK ½ phosphorylation similar to that of known antiangiogenic drug Sorafenib at all three concentrations 100 μM (46%,p= 0.003), 30 μM (64%,p= 0.0002) and 10 μM (91%,p= 0.0001). In a scratch assay model, whilst sorafenib at 3 μM was not able to limit migration after 8-hr compared to an untreated control (p = 0.0978), AH9 did (17.41%, p = 0.0079). Furthermore, AH9 was able to inhibit ERK ½ phosphorylation in a concentration dependent manner 100 μM (46%, p = 0.003), 30 μM (64%, p = 0.0002) and 10 μM (91%, p = 0.0001) compared to the VEGF control. These preliminary findings support that AH9 could be exerting antimigratory effects through the inhibition of the VEGF induced MAPK/ERK pathway. This forms the foundation for further studies to explore chalcone analogues in hope to aid current antiangiogenic therapeutic strategies as potential angiogenic inhibitors.
Numerical and analytical simulation of the growth of amyloid-β plaques
Authors: Kuznetsov Andrey V.
Published: September 2023

Numerical and analytical solutions were employed to calculate the radius of an amyloid-β (Aβ) plaque over time. To the author’s knowledge, this study presents the first model simulating the growth of Aβ plaques. Findings indicate that the plaque can attain a diameter of 50 μm after 20 years of growth, provided the Aβ monomer degradation machinery is malfunctioning. A mathematical model incorporates nucleation and autocatalytic growth processes using the Finke-Watzky model. The resulting system of ordinary differential equations was solved numerically, and for the simplified case of infinitely long Aβ monomer half-life, an analytical solution was found. Assuming that Aβ aggregates stick together and using the distance between the plaques as an input parameter of the model, it was possible to calculate the plaque radius from the concentration of Aβ aggregates. This led to the “cube root hypothesis,” positing that Aβ plaque size increases proportionally to the cube root of time. This hypothesis helps explain why larger plaques grow more slowly. Furthermore, the obtained results suggest that the plaque size is independent of the kinetic constants governing Aβ plaque agglomeration, indicating that the kinetics of Aβ plaque agglomeration is not a limiting factor for plaque growth. Instead, the plaque growth rate is limited by the rates of Aβ monomer production and degradation.
Mechanisms of Cell Size Regulation in Slow-GrowingEscherichia coliCells: Discriminating Models Beyond the Adder
Authors: Nieto César , Vargas-García César , Pedraza Juan Manuel , Singh Abhyudai
Published: September 2023

Under ideal conditions,Escherichia colicells divide after adding a fixed cell size, a strategy known as theadder. This concept applies to various microbes and is often explained as the division that occurs after a certain number of stages, associated with the accumulation of precursor proteins at a rate proportional to cell size. However, under poor media conditions,E. colicells exhibit a different size regulation. They are smaller and follow asizer-likedivision strategy where the added size is inversely proportional to the size at birth. We explore three potential causes for this deviation: precursor protein degradation, nonlinear accumulation rate, and a threshold size termed thecommitment size. These models fit mean trends but predict different distributions given the birth size. To validate these models, we used the Akaike information criterion and compared them to open datasets of slow-growingE. colicells in different media. the degradation model could explain the division strategy for media where cells are larger, while the commitment size model could account for smaller cells. The power-law model, finally, better fits the data at intermediate regimes.
Non-preferential, but detrimental accumulation of macrophages with clonal hematopoiesis-driver mutations in cardiovascular tissues
Authors: Dederichs Tsai-Sang , Yerdenova Assel , Horstmann Hauke , Vico Tamara , Nübling Simone , Peyronnet Remi , von zur Muehlen Constantin , Heidt Timo , Wolf Dennis , Westermann Dirk , Hilgendorf Ingo
Published: September 2023

Clonal hematopoiesis of indeterminate potential (CHIP) is an acquired genetic risk factor for cardiovascular (CV) disease, supposedly mediated by pro-inflammatory recruited monocytes1–15. However, how these cells and their progeny behave in the CV tissue remains unclear. Here, we studied human carotid artery plaque and heart tissue samples fromDNMT3AorTET2mutation carriers to quantify the relative accumulation of mutated macrophages and to characterize tissue macrophages from carriers compared to non-carriers. Using droplet digital polymerase chain reaction (ddPCR), we detected similar sizes of CHIP clones in circulating monocytes and macrophages from atheromas and heart tissues, even among CCR2+ (infiltrative), and CCR2– (resident) cardiac macrophages. Using bulk RNA-sequencing (RNA-seq), we revealed a pro-inflammatory gene profile of myeloid cells from CHIP carriers compared to non-carriers. In summary, quantitatively, CHIP mutated myeloid cells did not preferentially accumulate in CV tissues, but qualitatively, they expressed a more disease-prone phenotype.
omicsMIC: a Comprehensive Benchmarking Platform for Robust Comparison of Imputation Methods in Mass Spectrometry-based Omics Data
Authors: Lin Weiqiang , Ji Jiadong , Su Kuan-Jui , Qiu Chuan , Tian Qing , Zhao Lan-Juan , Luo Zhe , Shen Hui , Wu Chong , Deng Hongwen
Published: September 2023

Mass spectrometry is a powerful and widely used tool for generating proteomics, lipidomics, and metabolomics profiles, which is pivotal for elucidating biological processes and identifying biomarkers. However, missing values in spectrometry-based omics data may pose a critical challenge for the comprehensive identification of biomarkers and elucidation of the biological processes underlying human complex disorders. To alleviate this issue, various imputation methods for mass spectrometry-based omics data have been developed. However, a comprehensive and systematic comparison of these imputation methods is still lacking, and researchers are frequently confronted with a multitude of options without a clear rationale for method selection. To address this pressing need, we developed omicsMIC (mass spectrometrybasedomicswith Missing values Imputation methods Comparison platform), an interactive platform that provides researchers with a versatile framework to simulate and evaluate the performance of 28 diverse imputation methods. omicsMIC offers a nuanced perspective, acknowledging the inherent heterogeneity in biological data and the unique attributes of each dataset. Our platform empowers researchers to make data-driven decisions in imputation method selection based on real-time visualizations of the outcomes associated with different imputation strategies. The comprehensive benchmarking and versatility of omicsMIC make it a valuable tool for the scientific community engaged in mass spectrometry-based omics research. OmicsMIC is freely available athttps://github.com/WQLin8/omicsMIC.
Genomic analysis reveals limited hybridization among three giraffe species in Kenya
Authors: Coimbra Raphael T. F. , Winter Sven , Muneza Arthur , Fennessy Stephanie , Otiende Moses , Mijele Domnic , Masiaine Symon , Stacy-Dawes Jenna , Fennessy Julian , Janke Axel
Published: September 2023

Background

In the speciation continuum the strength of reproductive isolation varies, and species boundaries are blurred by gene flow. Interbreeding among giraffe (Giraffaspp.) in captivity is known and anecdotal reports of natural hybrids exist. In Kenya, Nubian (G. camelopardalis camelopardalis), reticulated (G. reticulata), and Masai giraffe sensu stricto (G. tippelskirchi tippelskirchi) are parapatric, and thus the country might be a melting pot for these taxa. We analyzed 128 genomes of wild giraffe, 113 newly sequenced, representing these three taxa.

Results

We found varying levels of Nubian ancestry in 13 reticulated giraffe sampled across the Laikipia Plateau most likely reflecting historical gene flow between these two lineages. Although comparatively weaker signs of ancestral gene flow and potential mitochondrial introgression from reticulated into Masai giraffe were also detected, estimated admixture levels between these two lineages are minimal. Importantly, contemporary gene flow between East African giraffe lineages was not statistically significant. Effective population sizes have declined since the Late Pleistocene, more severely for Nubian and reticulated giraffe.

Conclusions

Despite historically hybridizing, these three giraffe lineages have maintained their overall genomic integrity suggesting effective reproductive isolation, consistent with the previous classification of giraffe into four species.