bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide mapping of main histone modifications and coordination regulation of metabolic genes under salt stress in pea (Pisum sativum L)
Authors: Wan Heping , Cao Lan , Wang Ping , Hu Hanbing , Guo Rui , Chen Jingdong , Zhao Huixia , Zeng Changli , Liu Xiaoyun
Published: September 2024

Pea occupy a key position in modern biogenetics, playing multifaceted roles as food, vegetable, fodder, and green manure. However, due to the complex nature of its genome and the prolonged unveiling of high-quality genetic maps, research into the molecular mechanisms underlying pea development and stress responses has been significantly delayed. Furthermore, the exploration of its epigenetic modification profiles and associated regulatory mechanisms remains uncharted. This research conducted a comprehensive investigation of four specific histone marks, namely H3K4me3, H3K27me3, H3K9ac, and H3K9me2, and the transcriptome in pea under normal conditions, and established a global map of genome-wide regulatory elements, chromatin states, and dynamics based on these major modifications. Our analysis identified epigenomic signals across ~82.6% of the genome. Each modification exhibits distinct enrichment patterns: H3K4me3 is predominantly associated with the gibberellin response pathway, H3K27me3 is primarily associated with auxin and ethylene responses, and H3K9ac is primarily associated with negative regulatory stimulus responses. We also identified a novel bivalent chromatin state (H3K9ac-H3K27me3) in pea, which is related to their development and stress response. Additionally, we unveil that these histone modifications synergistically regulate metabolic-related genes, influencing metabolite production under salt stress conditions. Our findings offer a panoramic view of the major histone modifications in pea, elucidate their interplay, and highlight their transcriptional regulatory roles during salt stress.
Genome-wide screen and multi-omics analysis reveal OGT1 participate in the biosynthesis of safflower flavonoid glycosides
Authors: Xian Bin , Zhou Yanxun , Hu Yueying , Peng Yanni , Song Xiaominting , Xi Ziqing , Li Yuhang , Yan Jie , Ren Chaoxiang , Pei Jin , Chen Jiang
Published: September 2024

Safflower, an economic crop, is renowned for its flowers, which are widely used in medicines for treating cardiovascular and cerebrovascular diseases and in dyes for food and industry. The utility of safflower depends on its flavonoid glycosides. Therefore, the biosynthesis of safflower flavonoid glycosides has been a focus of attention, but the present mechanisms remain poorly understood. This study aims to identify functional genes associated with flavonoid glycoside biosynthesis in safflower through a comprehensive approach that integrates whole-genome screen and multi-omics correlation studies. CYP and UGT are two crucial genes families involved in flavonoid glycoside biosynthesis. We have screened 264 CYP genes and 140 UGT genes in the genome of safflower and conducted analyzes including phylogenetic relationships, conserved motifs, gene structures, cis-acting elements, and chromosome mapping, which provided extensive and comprehensive data on the CYP and UGT gene families. Integration of phenotype and metabolic data from safflower different tissues helped narrow down the screening by confirming that HSYA is synthesized only in flowers. Based on the gene expression patterns and phylogenetic analysis, CtOGT1 was ultimately identified, which could catalyze the generation of glycosides using various flavonoid substrates and exhibited strong substrate affinity. Moreover, molecular docking studies elucidated CtOGT1’s highly active intrinsic mechanism. In conclusion, this study effectively identified genes responsible for flavonoid glycoside biosynthesis in safflower through the integration of whole-genome screen and multi-omics analysis, established a comprehensive foundation of data, methodology, and experimental evidence for further elucidating the pathways of safflower flavonoid glycoside biosynthesis.
Decoding the genetic basis of secretory tissues in plants
Authors: Han Yuepeng
Published: September 2024

Although plant secretory tissues play important roles in host defense against herbivores and pathogens and the attraction of insect pollinators, their genetic control remains elusive. Here, it is focused that current progress has been made in the genetic regulatory mechanisms underpinning secretory tissue development in land plants. C1HDZ transcription factors (TFs) are found to play crucial roles in the regulation of internal secretory tissues in liverworts and Citrus as well as external secretory tissues in peach. C1HDZ TFs regulate secretory tissue development via synergistic interaction with AP2/ERF and MYC TFs. Thus, a set of genes are speculated to be recruited convergently for the formation of secretory tissues in land plants.
Sign Changes of the Error Term in the Piltz Divisor Problem
Authors: Baluyot Siegfred , Castillo Cruz
Published: September 2024

We study the function $\Delta _{k}(x):=\sum _{n\leq x} d_{k}(n) - \mbox{Res}_{s=1} ( \zeta ^{k}(s) x^{s}/s )$, where $k\geq 3$ is an integer, $d_{k}(n)$ is the $k$-fold divisor function, and $\zeta (s)$ is the Riemann zeta-function. For a large parameter $X$, we show that if the Lindelöf hypothesis (LH) is true, then there exist at least $X^{\frac{1}{k(k-1)}-\varepsilon }$ disjoint subintervals of $[X,2X]$, each of length $X^{1-\frac{1}{k}-\varepsilon }$, such that $|\Delta _{k}(x)|\gg x^{\frac{1}{2}-\frac{1}{2k}}$ for all $x$ in the subinterval. In particular, $\Delta _{k}(x)$ does not change sign in any of these subintervals. If the Riemann hypothesis (RH) is true, then we can improve the length of the subintervals to $\gg X^{1-\frac{1}{k}} (\log X)^{-k^{2}-2}$. These results may be viewed as higher-degree analogues of theorems of Heath-Brown and Tsang, who studied the case $k=2$, and Cao, Tanigawa, and Zhai, who studied the case $k=3$. The first main ingredient of our proofs is a bound for the second moment of $\Delta _{k}(x+h)-\Delta _{k}(x)$. We prove this bound using a method of Selberg and a general lemma due to Saffari and Vaughan. The second main ingredient is a bound for the fourth moment of $\Delta _{k}(x)$, which we obtain by combining a method of Tsang with a technique of Lester.
Modernizing behavioral parent training program for ADHD with mHealth strategies, telehealth groups, and health behavior curriculum: a randomized pilot trial
Authors: Tandon Pooja S , Gabert Tess , Kuhn Michelle , Tran Nguyen , Ola Cindy , Sullivan Erin , Zhou Chuan , Stein Mark , Mendoza Jason A , Sasser Tyler , Gonzalez Erin
Published: September 2024

Objective

Parent behavior management training (BMT) is an evidence-based yet underutilized tool to treat children with ADHD and address related health disparities. This pilot study investigated the acceptability and feasibility of a novel, health behavior-, and technology-adapted BMT (LEAP) vs. standard BMT.

Methods

The weekly 9-session LEAP telemedicine group program is based on a standard BMT curriculum enhanced with strategies for supporting optimal child sleep, problematic media use (PMU), and physical activity, including wrist-worn activity trackers. Children ages 6–10 years with ADHD and their caregivers were randomized to LEAP or standard BMT. Acceptability and feasibility were tracked. Caregivers completed standardized measures, and children wore hip-worn accelerometers for 1 week at baseline, postintervention (10 weeks), and follow-up (20 weeks).

Results

84 parent/child dyads were randomized to LEAP or standard BMT, with high and comparable acceptability and feasibility. Both treatment groups demonstrated decreased ADHD symptoms and improved executive functions postintervention (p < .0001), maintained at follow-up. Average accelerometer-measured MVPA decreased and sleep duration remained unchanged, while PMU and bedtime resistance improved for both groups.

Conclusions

LEAP is highly feasible and acceptable, and yielded similar initial clinical and health behavior improvements to standard BMT. Innovative and targeted supports are needed to promote healthy behaviors in children with ADHD.
Integrating testing volume into bandit algorithms for infectious disease surveillance
Authors: Warren Joshua L , Prunas Ottavia , Paltiel A David , Thornhill Thomas , Gonsalves Gregg S
Published: September 2024

Mobile testing services provide opportunities for active surveillance of infectious diseases for hard-to-reach and/or high-risk individuals who do not know their disease status. Identifying as many infected individuals as possible is important for mitigating disease transmission. Recently, multi-armed bandit sampling approaches have been adapted and applied in this setting to maximize the cumulative number of positive tests collected over time. However, these algorithms have not considered the possibility of variability in the number of tests administered across testing sites. What impact this variability has on the ability of these approaches to maximize yield is currently unknown. Therefore, we investigate this question by extending existing sampling frameworks to directly account for variability in testing volume while also maintaining the computational tractability of the previous methods. Through a simulation study based on human immunodeficiency virus infection characteristics in the Republic of the Congo (Congo-Brazzaville) as well as an application to COVID-19 testing data in Connecticut, we find improved long- and short-term performances of the new methods compared to several existing approaches. Based on these findings and the ease of computation, we recommend use of the newly developed methods for active surveillance of infectious diseases when variability in testing volume may be present.
Gene silencing in broomrapes and other parasitic plants of the Orobanchaceae family: mechanisms, considerations, and future directions
Authors: Zainali Nariman , Alizadeh Houshang , Delavault Philippe
Published: September 2024

Holoparasites of the Orobanchaceae family are devastating pests causing severe damage to many crop species, and are nearly impossible to control with conventional methods. During the past few decades, RNAi has been seen as a promising approach to control various crop pests. The exchange of small RNAs (sRNAs) between crops and parasitic plants has been documented, indicating potential for the development of methods to protect them via the delivery of the sRNAs to parasites, a method called host-induced gene silencing (HIGS). Here we describe various approaches used for gene silencing in plants and suggest solutions to improve the long-distance movement of the silencing triggers to increase the efficiency of HIGS in parasitic plants. We also investigate the important biological processes during the life cycle of the parasites, with a focus on broomrape species, providing several appropriate target genes that can be used, in particular, in multiplex gene silencing experiments. We also touch on how the application of nanoparticles can improve the stability and delivery of the silencing triggers, highlighting its potential for control of parasitic plants. Finally, suggestions for further research and possible directions for RNAi in parasitic plants are provided.
A Systematic Review of the Effect of Gene–Lifestyle Interactions on Metabolic-Disease-Related Traits in South Asian Populations
Authors: Bineid Manahil M , Ventura Eduard F , Samidoust Aryan , Radha Venkatesan , Anjana Ranjit Mohan , Sudha Vasudevan , Walton Gemma E , Mohan Viswanathan , Vimaleswaran Karani Santhanakrishnan
Published: September 2024

Context

Recent data from the South Asian subregion have raised concern about the dramatic increase in the prevalence of metabolic diseases, which are influenced by genetic and lifestyle factors.

Objective

The aim of this systematic review was to summarize the contemporary evidence for the effect of gene–lifestyle interactions on metabolic outcomes in this population.

Data sources

PubMed, Web of Science, and SCOPUS databases were searched up until March 2023 for observational and intervention studies investigating the interaction between genetic variants and lifestyle factors such as diet and physical activity on obesity and type 2 diabetes traits.

Data extraction

Of the 14 783 publications extracted, 15 were deemed eligible for inclusion in this study. Data extraction was carried out independently by 3 investigators. The quality of the included studies was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS), the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I), and the methodological quality score for nutrigenetics studies.

Data analysis

Using a narrative synthesis approach, the findings were presented in textual and tabular format. Together, studies from India (n = 8), Pakistan (n = 3), Sri Lanka (n = 1), and the South Asian diaspora in Singapore and Canada (n = 3) reported 543 gene–lifestyle interactions, of which 132 (∼24%) were statistically significant. These results were related to the effects of the interaction of genetic factors with physical inactivity, poor sleep habits, smoking, and dietary intake of carbohydrates, protein, and fat on the risk of metabolic disease in this population.

Conclusions

The findings of this systematic review provide evidence of gene–lifestyle interactions impacting metabolic traits within the South Asian population. However, the lack of replication and correction for multiple testing and the small sample size of the included studies may limit the conclusiveness of the evidence. Note, this paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.

Systematic Review Registration

PROSPERO registration No. CRD42023402408.
Some Polyphenolic Compounds as Potential Therapeutic Agents in Cervical Cancer: The Most Recent Advances and Future Prospects
Authors: Sanlier Nazlı Tunca , Saçinti Koray Görkem , Türkoğlu İnci , Sanlier Nevin
Published: September 2024

The leading causes of cancer include gradual changes in regulatory proteins, dysregulated cell-signaling pathways, dysfunction of apoptosis, and oxidative stress. Consuming polyphenols from food sources has been proven to have strong connections with ameliorating specific physiological biomarkers along with other elements concerning cancer. Recent studies have focused on polyphenols’ molecular mechanisms of action and anticancer and chemopreventive properties and effects in the treatment of different types of cancer. Polyphenols participate in the regulation of numerous cellular mechanisms alongside signaling pathways through their effects on inflammation, cellular proliferation, apoptosis, and partially via epigenetic alterations in cervical cancer. A number of animal models and cell and human studies have indicated the use of polyphenols to be safe and tolerable. Thus, it would be fair to state that, with their advantages vis-à-vis lack of toxicity, cost, and access, and with the positive clinical results, polyphenols have a potential to make a difference in cancer treatment. The present review examined the chemical and physical properties, analogs, metabolites, and mechanisms of physiological activities of various polyphenols and how they may affect the incidence rate and management of cervical cancer. Therefore, this review constitutes a starting point to examine the potential applications for cervical cancer.
RAPID ALKALINIZATION FACTOR 22 is a key modulator of the root hair growth responses to fungal ethylene emissions in Arabidopsis
Authors: Morcillo Rafael Jorge León , Leal-López Jesús , Férez-Gómez Alberto , López-Serrano Lidia , Baroja-Fernández Edurne , Gámez-Arcas Samuel , Tortosa Germán , López Leonel E , Estevez José Manuel , Doblas Verónica G , Frías-España Laura , García-Pedrajas María Dolores , Sarmiento-Villamil Jorge , Pozueta-Romero Javier
Published: September 2024

In Arabidopsis (Arabidopsis thaliana (L.) Heynh), exposure to volatile compounds (VCs) emitted by Penicillium aurantiogriseum promotes root hair (RH) proliferation and hyper-elongation through mechanisms involving ethylene, auxin, and photosynthesis signaling. In addition, this treatment enhances the levels of the small signaling peptide RAPID ALKALINIZATION FACTOR 22 (RALF22). Here, we used genetics to address the role of RALF22 in fungal VC-promoted RH growth and to identify the bioactive fungal VC. We found that RHs of ralf22 and feronia (fer-4) plants impaired in the expression of RALF22 and its receptor FERONIA, respectively, responded weakly to fungal VCs. Unlike in wild-type roots, fungal VC exposure did not enhance RALF22 transcript levels in roots of fer-4 and ethylene- and auxin-insensitive mutants. In ralf22 and fer-4 roots, this treatment did not enhance the levels of ERS2 transcripts encoding one member of the ethylene receptor family and those of some RH-related genes. RHs of ers2-1 and the rsl2rsl4 double mutants impaired in the expression of ERS2 and the ethylene- and auxin-responsive ROOT HAIR DEFECTIVE 6-LIKE 2 and 4 transcription factors, respectively, weakly responded to fungal VCs. Moreover, roots of plants defective in photosynthetic responsiveness to VCs exhibited weak RALF22 expression and RH growth responses to fungal VCs. VCs of ΔefeA strains of P. aurantiogriseum cultures impaired in ethylene synthesis weakly promoted RH proliferation and elongation in exposed plants. We conclude that RALF22 simultaneously functions as a transcriptionally regulated signaling molecule that participates in the ethylene, auxin, and photosynthesis signaling-mediated RH growth response to fungal ethylene emissions and regulation of ethylene perception in RHs.
Validation of a Clinical Teaching Competency Framework for Physical Therapists: A Mixed-Methods Approach
Authors: Sharp Amanda , Bilyeu Catherine , Wengrovius Carissa , Myers Katherine
Published: September 2024

Objective

A competency framework for clinical teaching in physical therapy was established in a recent study. Validation of competency frameworks requires multiple steps, including consideration of end-user perceptions of value and utility. The purpose of this study was to further validate the Clinical Teaching Competency Framework by gathering input specifically from clinical education faculty.

Methods

This study used an explanatory sequential mixed-methods approach to seek input from clinical instructors (CIs) and site coordinators of clinical education (SCCE) from diverse practice areas and geographic regions. A survey invited participation from active clinical education faculty, and survey respondents were invited to participate in a focus group. Two focus groups were held via Zoom.

Results

Survey responses from those holding roles of CI (59.3%), SCCE (11.3%), and CI/SCCE (29.4%) indicated support for the competency framework, including perceived value to their role (93.1%) and improvement in the quality of clinical education (94.1%). Concern regarding the ease of utilization of the framework was indicated by 24% of respondents. There were no statistically significant differences in responses based on role or credentials. The focus groups resulted in an overarching theme of collective impact, with 4 subthemes: assessment, CI development, implementation, and guidelines.

Conclusion

Clinical education faculty perceive value and utility in the Clinical Teaching Competency Framework. Implementation of the framework should be collaborative and consistent across academic and clinical education programs.

Impact

This study moves the profession one step closer to the use of a competency framework specifically targeted at clinical teaching in physical therapy. Clinical education faculty will be primary users of a competency framework, and buy-in from this user group is key to implementation. Continued efforts to validate this framework contribute to addressing the need for CI development and support in delivering excellence in clinical education.
Safety of rTMS for Schizophrenia: A Systematic Review and Meta-analysis
Authors: Blyth Sophia H , Cruz Bosch Claudia , Raffoul Julian J , Chesley Jordyn , Johnson Benjamin , Borodge Darara , Sagarwala Raza , Masters Ross , Brady Roscoe O , Vandekar Simon , Ward Heather Burrell
Published: September 2024

Background and Hypothesis

Current treatments for schizophrenia are only partially effective, and there are no medications for negative symptoms or cognitive impairment. Neuromodulation, such as repetitive transcranial magnetic stimulation (rTMS), has potential as a novel intervention for schizophrenia. Prior to clinical use, rTMS should have demonstrated safety in a large schizophrenia population. However, the safety profile of rTMS in schizophrenia is not well characterized, and regulatory agencies have expressed concern about safety in this population.

Study Design

We conducted a systematic review with meta-analysis of rTMS studies in schizophrenia. We searched PubMed, the Cochrane Library, PsycINFO, and Science Citation Index Expanded for rTMS studies in schizophrenia that reported adverse effects. We extracted the number of participants who experienced an adverse effect and calculated the prevalence of each adverse effect for active or sham rTMS. We tested the difference between the prevalence of events in the active and sham conditions. We assessed risk of bias using the Cochrane Handbook.

Study Results

The initial search identified 1472 studies. After screening, 261 full-text studies were assessed, and 126 met inclusion criteria (N = 4122 total subjects). The prevalence of headache or scalp pain, dizziness or syncope, facial twitching, and nausea was higher for active rTMS compared to sham (P < .05). The prevalence of all other adverse effects, including seizure, was not different between active and sham rTMS.

Conclusions

rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure, compared to the general population.
A p21 reporter iPSC line for evaluating CRISPR-Cas9 and vector-induced stress responses
Authors: Sun Yi-Dan , Li Guo-Hua , Zhang Feng , Cheng Tao , Zhang Jian-Ping , Zhang Xiao-Bing
Published: September 2024

CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.

Highlights Established a p21-mNeonGreen reporter iPSC line to track activation of the TP53-p21 pathway.

Found a direct correlation between p21-mNeonGreen expression and indel frequencies, aiding in gRNA screening.

Showed that LVs are preferable over AAVs for certain cells due to lower p21 activation, with viral promoter choice impacting p21 response.
Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia
Authors: Sanz-Nogués Clara , Keane Alan J , Creane Michael , Hynes Sean O , Chen Xizhe , Lyons Caomhán J , Horan Emma , Elliman Stephen J , Goljanek-Whysall Katarzyna , O’Brien Timothy
Published: September 2024

Peripheral arterial disease (PAD) is associated with lower-extremity muscle wasting. Hallmark features of PAD-associated skeletal muscle pathology include loss of skeletal muscle mass, reduced strength and physical performance, increased inflammation, fibrosis, and adipocyte infiltration. At the molecular level, skeletal muscle ischemia has also been associated with gene and microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have been shown to enhance muscle regeneration and improve muscle function in various skeletal muscle injuries. This study aimed to evaluate the effects of intramuscularly delivered human umbilical cord-derived MSCs (hUC-MSCs) on skeletal muscle ischemia. Herein, we report an hUC-MSC-mediated amelioration of ischemia-induced skeletal muscle atrophy and function via enhancement of myofiber regeneration, reduction of tissue inflammation, adipocyte accumulation, and tissue fibrosis. These changes were observed in the absence of cell-mediated enhancement of blood flow recovery as measured by laser Doppler imaging. Furthermore, reduced tissue fibrosis in the hUC-MSC-treated group was associated with upregulation of miR-1, miR-133a, and miR-29b and downregulation of targeted pro-fibrotic genes such as Col1a1 and Fn1. Our results support the use of hUC-MSCs as a novel approach to reduce fibrosis and promote skeletal muscle regeneration after ischemic injury in patients with PAD.
Functional evolution of facial bristle feathers in Old World passerines
Authors: Minias Piotr , Barczyk Julia , Davaasuren Batmunkh , Erdenechimeg Tuvshinjargal , Remisiewicz Magdalena
Published: September 2024

Many bird species have vaneless hair-like feathers in the frontal area of the head (facial bristles). Several alternative hypotheses on the functional significance of avian facial bristles have been proposed, including aid in insect capture, eye protection, and mechanosensory sensitivity. Here, we used a phylogenetically-informed comparative approach to examine functional evolution of facial bristle feathers in Old World passerines (Passeriformes). For this purpose, we quantified the number and length of facial bristles located at the base of the upper beak (upper rictal bristles) in over 1300 birds representing 73 species and 21 families, and tested for evolutionary associations of these traits with species ecology, biogeography, life history, and morphology. We found that more numerous and longer rictal bristles have evolved in association with invertivory and omnivory. The number or length of rictal bristles was also linked to aerial foraging, foraging in low vegetation, occupancy of shrubland habitats, and migration. All these evolutionary correlations suggest that avian rictal bristles may serve multiple non-exclusive functions related to insect capture and tactile sensing. Comparisons with previous research provide support for scale dependence in avian rictal bristle evolution and decoupling of evolutionary processes at different levels of phylogenetic organization.
Biodemography of Human Aging (Gompertz–Makeham Law) Applied to Surgical Mortality Modeling: A Retrospective National Cohort Study
Authors: Campbell Doug , Boyle Luke , Webb Mike , Mistry Manisha , Short Timothy G.
Published: September 2024

Background:

The Gompertz–Makeham law describes a characteristic pattern of mortality in human populations where the death rate is near constant between ages 18 and 30 yr (Makeham law) and rises exponentially thereafter (Gompertz law). This pattern has not been described in surgical populations, but if true, it would have important implications for understanding surgical risk and design and interpretation of surgical risk models. The aim of this study was to determine whether the Gompertz–Makeham law applies to perioperative mortality risk and the conditions under which it may apply.

Methods:

This study examined the relationship between age and 1-month postoperative all-cause mortality risk in a 10-yr New Zealand administrative dataset comprising 5,615,100 surgical procedures from 2007 to 2016. The dataset includes patient and surgical factors including procedures, American Society of Anesthesiologists (ASA; Schaumburg, Illinois) Physical Status score, diagnoses, and other relevant details. Semilogarithmic graphs of mortality risk and age were plotted. Linear regression models were fitted, with regression line slope and Pearson correlation coefficient calculated.

Results:

The primary outcome occurred in 114,782 (2.0%) of 5,615,100 included participants. The Gompertz–Makeham law seems to apply to the national surgical population as a whole (slope = 0.0241; R
2 = 0.971). The law applies in all subgroups studied including sex, ASA Physical Status, surgical acuity, surgical severity category, cancer status, and ethnicity (slopes, 0.0066 to 0.0307; R
2, 0.771 to 0.990). Important interactions were found between age, mortality risk, and three high-risk groups (cancer diagnosis, ASA Physical Status IV to V, and high surgical severity).

Conclusions:

The Gompertz–Makeham law seems to apply in a national cohort of surgical patients. The inflection point for increased 1-month risk is apparent at age 30 yr. A strict exponential rise in mortality risk occurs thereafter. This finding improves the understanding of surgical risk and suggests a concept-driven approach to improve modeling of age and important interactions in future surgical risk models.
Pediatric Monteggia Fracture-dislocations and Their Variants: An Analysis of Outcomes and Complications Over a 10-year Period
Authors: Haft Mark , Codd Casey M. , May Catherine C. , Conroy Julia L. , Abzug Joshua M.
Published: September 2024

Objective:

Monteggia fracture-dislocation variants have been well documented in adults, but most of the literature in the pediatric population is in the form of case reports. These injuries present differently in children due to the presence of immature radiocapitellar epiphyses and the flexibility of the joint that is more prone to subluxation, contributing to occult presentations and/or misdiagnoses. The purpose of this study is to investigate the outcomes and complications of true Monteggia fracture-dislocations compared with their variants in the pediatric population.

Methods:

A retrospective review was performed of all patients 17 years of age and younger who sustained a true Monteggia fracture-dislocation or a Monteggia fracture-dislocation variant over a 10-year period. Patient demographics, mechanisms of injury, fracture pattern, Bado and Letts classification, treatment (operative or conservative), and complications were recorded.

Results:

Of the 89 patients identified, 17 (19.1%) had true Monteggia fracture dislocations, and 72 (80.9%) had a Monteggia fracture-dislocation variant. The most common Monteggia fracture-dislocation variant was an olecranon fracture and concomitant radial neck fracture (65.3%, n = 47). Of the Monteggia fracture-dislocation variants, 83.3% (n = 60) were treated nonoperatively with closed reduction and immobilization or immobilization alone, whereas only 23.5% (n = 4) of the true Monteggia fracture-dislocation injuries were treated nonoperatively with closed reduction and immobilization. Overall, 14 (15.7%) patients had complications during the course of treatment, including 12 (16.7%) Monteggia fracture-dislocation variants and 2 (11.8%) true Monteggia fracture-dislocations. The most common complications were loss of range of motion (n = 6, 42.9%, all of which were nondisplaced variants), loss of reduction (n = 4, 28.6%, including 2 nondisplaced variants, 1 displaced variant, and 1 true Monteggia fracture dislocation), and malunion or nonunion (n = 2, 14.3%, both nondisplaced variants).

Conclusion:

Pediatric Monteggia fracture-dislocation variants are much more common than true pediatric Monteggia fracture-dislocations. Monteggia fracture-dislocation variants have similar complication rates to true Monteggia fracture-dislocations overall, however, nondisplaced variants exhibited a higher complication rate when treated operatively. Further studies are warranted to assess specific fracture patterns and their associated treatments that result in varying complication rates.

Level of Evidence:

Level III—retrospective comparison study.
Updated Canadian Clinical Practice Guideline for the Rehabilitation of Adults With Moderate to Severe Traumatic Brain Injury: Behavioral Recommendations
Authors: MacKenzie Heather M. , Velikonja Diana , Devito Julia , Devito Lauren , Patsakos Eleni M. , Bayley Mark , Teasell Robert , Mehta Swati
Published: September 2024

Objective:

Behavioral changes following moderate to severe traumatic brain injury (MSTBI) are common and can include agitation or aggression, reduced arousal or apathy, and inappropriate sexual behavior. These changes can negatively affect recovery, function, and quality of life. Pharmacological and nonpharmacological interventions are often used to address these challenges; however, there is limited evidence regarding the effectiveness of these treatments. This article will summarize the updated recommendations for the assessment and management of behavioral changes in adults after MSTBI.

Design:

A systematic search was conducted by the evidence-based review of moderate to severe acquired brain injury to identify new and relevant articles. Expert panels reviewed and discussed the new and existing evidence, evaluated its quality, and added, removed, or modified recommendations and tools as needed. A consensus process was followed to achieve agreement on recommendations.

Results:

The 2023 Canadian Clinical Practice Guideline for the Rehabilitation of Adults with Moderate to Severe Traumatic Brain Injury (CAN-TBI 2023) includes 21 recommendations regarding best practices for the assessment and management of behavioral disorders post-MSTBI. Fifteen recommendations remained unchanged, and 6 recommendations were updated. Eight recommendations are based on level B evidence and 13 on level C evidence. There are no recommendations based on level A evidence. The guideline also includes a step-by-step algorithm for clinicians to follow outlining an approach to the assessment and management of agitation and aggression.

Conclusion:

CAN-TBI 2023 will assist clinicians in the assessment and safe and effective management of behavioral changes post-MSTBI. The guideline is informed by a growing scientific database although there is a need for additional high-quality research to better guide the assessment and management of this complex patient population.
Evidence-Based Review of Randomized Controlled Trials of Interventions for Mental Health Management Post-Moderate to Severe Traumatic Brain Injury
Authors: Flores-Sandoval Cecilia , Teasell Robert , MacKenzie Heather M. , McIntyre Amanda , Barua Ujjoyinee , Mehta Swati , Bayley Mark , Bateman Emma A.
Published: September 2024

Objective:

To present an evidence-based review of randomized controlled trials (RCTs) evaluating interventions for mental health post-moderate to severe traumatic brain injury (post-MSTBI), as part of an extensive database that has been conceptualized as a living systematic review.

Methods:

Systematic searches were conducted for RCTs published in the English language in MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO, up to and including December 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodological quality of RCTs was assessed using the Physiotherapy Evidence Database scale, and the level of evidence was assigned using a modified Sackett scale.

Results:

Eighty-seven RCTs examining mental health interventions and outcome measures post-MSTBI were included. These studies collectively enrolled 6471 participants. A total of 41 RCTs (47.1%) were conducted in the United States and 56 studies (64.4%) were published after 2010. A total of 62 RCTs (71.3%) examined nonpharmacological interventions and 25 RCTs (28.7%) examined pharmacological interventions. Effective pharmacological treatments included desipramine and cerebrolysin; methylphenidate and rivastigmine showed conflicting evidence. Cognitive behavioral therapy (CBT) was found to be effective for hopelessness, stress, and anxiety, compared to usual care; however, it may be as effective as supportive psychotherapy for depression. CBT combined with motivational interviewing may be as effective as CBT combined with nondirective counseling for depression, stress, and anxiety. Acceptance and commitment therapy was effective for anxiety, stress, and depression. Tai Chi, dance, and walking appeared to be effective for depression and stress, while other nonpharmacological treatments such as peer mentoring showed limited effectiveness.

Conclusion:

This evidence-based review provides a comprehensive overview of the research landscape of RCTs addressing mental health post-MSTBI. The findings from these RCTs may be valuable for health care professionals, researchers, and policymakers involved in the field of mental health and neurorehabilitation.
DIABETIC RETINOPATHY LESION TYPES AND DISTRIBUTION ON ULTRAWIDE FIELD IMAGING AND THE RISK OF DISEASE WORSENING OVER TIME
Authors: Silva Paolo S. , Liu Danni , Aiello Lloyd P. , Melia Michele , Sun Jennifer K. ,   for the DRCR Retina Network
Published: September 2024

Purpose:

To evaluate the effect of diabetic retinopathy (DR) lesion type (hemorrhages and/or microaneurysms, intraretinal microvascular abnormalities, new vessels elsewhere, and venous beading), severity, and distribution on disease worsening based on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale.

Methods:

Post hoc analysis of a multicenter observational study of 544 eyes with nonproliferative DR and an Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale score of Level 35 to 53. Disease worsening was defined as Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale worsening by ≥2 steps from baseline or receipt of DR treatment over 4 years. DR lesions were evaluated based on the entire visible area in the ultrawide field color (UWF-color) and UWF-fluorescein angiography images.

Results:

A significantly greater risk of disease worsening was associated with the presence of more severe lesion grades outside the Early Treatment Diabetic Retinopathy Study fields for hemorrhages and/or microaneurysms (hazard ratio: 1.74 [95% confidence interval, 1.28–2.36]) on UWF-color and for hemorrhages and/or microaneurysms (1.90 [1.38–2.61]), intraretinal microvascular abnormalities (1.68 [1.13–2.49]), and new vessels elsewhere (1.99 [1.36–2.93]) on UWF-fluorescein angiography.

Conclusion:

These results suggest that features on UWF-color and UWF-fluorescein angiography may provide additional prognostic value in determining the risk of disease worsening. The use of UWF-fluorescein angiography improves identification of DR lesions and disease progression. However, the optimal method of disease risk assessment on UWF imaging still needs to be determined.
Outcomes After Exoscopic Versus Microscopic Ossicular Chain Reconstruction
Authors: Fan Caleb J. , Lucas Jacob C. , Conway Robert M. , Kato Masanari G. , Babu Seilesh C.
Published: September 2024

Objective

To analyze the outcomes of exoscopic versus microscopic ossicular chain reconstruction (OCR).

Study Design

Retrospective chart review.

Setting

Tertiary care otology-neurotology practice.

Patients

Adult subjects with a diagnosis of ossicular discontinuity from 2018 to 2022.

Interventions

Exoscopic or microscopic primary OCR (without mastoidectomy) with a partial ossicular replacement prosthesis (PORP) or total ossicular replacement prosthesis (TORP).

Main Outcome Measures

Audiometric outcomes at 3 months and 1 year postoperatively including bone and air pure tone averages (PTA), air-bone gap (ABG), change in ABG, speech reception threshold (SRT), and word recognition score (WRS). Secondary outcomes included operative time and complication rates of primary and delayed graft failure, tympanic membrane lateralization, prosthesis extrusion, cerebrospinal fluid leak, facial nerve injury, profound hearing loss, persistent tinnitus, and persistent vertigo.

Results

Sixty ears underwent primary OCR and were subdivided based on prosthesis type (PORP and TORP) and surgical approach (exoscope vs microscope). Exoscopic OCR was performed on 30 ears (21 PORP, 9 TORP), and microscopic OCR was performed on 30 ears (19 PORP, 11 TORP). In the overall group (PORP + TORP) and in the PORP and TORP subgroups, there were no significant differences in 1) demographics, 2) intraoperative findings, and 3) audiometric outcomes of bone and air PTA, ABG, change in ABG, SRT, and WRS at 1 year postoperatively. Operative time was 64.7 and 59.6 minutes for the exoscopic and microscopic group, respectively (p = 0.4, 95% CI [−16.4, 6.1], Cohen's D = 0.2).

Conclusions

Audiometric and surgical outcomes after exoscopic and microscopic OCR are comparable.
Gaps in knowledge and recurrent urinary tract infections in women
Authors: Zimmern Philippe
Published: September 2024

Purpose of review

The focus of this review is to present recent literature and gaps in knowledge (GIKs) surrounding the current and future treatment and prevention of uncomplicated recurrent urinary tract infections (rUTIs) in women.

Recent findings

Recurrent urinary tract infections are common, significantly reduce quality of life, and create a substantial economic burden to the healthcare system. They are disproportionately affecting the postmenopausal women. Antibiotics, which are used for the treatment and prophylaxis of uncomplicated rUTI, have become problematic, as there is a global rise in allergy and resistance to these agents and their use is associated with further antimicrobial resistance. Thus, in recent decades, several alternative, nonantibiotic approaches have been evaluated.

There is a critical need for a concerted and standardized methodology for diagnosing, treating, and monitoring women with rUTIs. Additionally, novel nonantibiotic alternative treatment and preventive measures for UTIs are desperately required to address the global issue of antibiotic recalcitrance in all age groups, and specifically older women. Research efforts have sought to develop alternative and more effective techniques; many of which appear to be promising, but require additional evaluation and validation through clinical trials.
Bridging the care gap: radiation therapy in elderly and frail cancer patients
Authors: Hircock Caroline , Lee Shing Fung , Raman Srinivas , Chuk Elizabeth , Chan Adrian W. , Chow Edward , Wong Henry C.Y.
Published: September 2024

Purpose of review

This review aims to address the gap in radiation therapy (RT) care for elderly cancer patients. It will discuss the barriers to implementing effective RT in elderly and frail patients with a focus on breast cancer and metastatic settings.

Recent findings

Recent studies indicate that SBRT provides better pain control for bone metastases compared to cEBRT, but elderly patients are underrepresented in these trials. Evidence on the effectiveness of geriatric assessment tools in predicting RT tolerance and toxicity is mixed, with some studies showing a correlation while others do not. Comprehensive geriatric assessments, though promising, are often impractical due to time and resource constraints.

There is a critical need for more inclusive research to better understand the risks and benefits of RT in elderly patients. Developing streamlined geriatric assessment tools and integrating them into clinical practice can enhance treatment personalization. Future studies should prioritize elderly populations to generate robust data, thereby improving RT outcomes and quality of life for this growing patient group.
A near-tight lower bound on the density of forward sampling schemes
Authors: Kille Bryce , Koerkamp Ragnar Groot , McAdams Drake , Liu Alan , Treangen Todd J.
Published: September 2024

Motivation

Samplingk-mers is a ubiquitous task in sequence analysis algorithms. Sampling schemes such as the often-used random minimizer scheme are particularly appealing as they guarantee at least onek-mer is selected out of everywconsecutivek-mers. Sampling fewerk-mers often leads to an increase in efficiency of downstream methods. Thus, developing schemes that have low density, i.e., have a small proportion of sampledk-mers, is an active area of research. After over a decade of consistent efforts in both decreasing the density of practical schemes and increasing the lower bound on the best possible density, there is still a large gap between the two.

Results

We prove a near-tight lower bound on the density of forward sampling schemes, a class of schemes that generalizes minimizer schemes. For smallwandk, we observe that our bound is tight whenk≡ 1 (modw). For largewandk, the bound can be approximated by. Importantly, our lower bound implies that existing schemes are much closer to achieving optimal density than previously known. For example, with the current default minimap2 HiFi settingsw= 19 andk= 19, we show that the best known scheme for these parameters, the double decycling-set-based minimizer of Pellow et al., is at most 3% denser than optimal, compared to the previous gap of at most 50%. Furthermore, whenk≡ 1 (modw) and the alphabet sizeσgoes to ∞, we show that mod-minimizers introduced by Groot Koerkamp and Pibiri achieve optimal density matching our lower bound.

Availability and implementation

Minimizer implementations:github.com/RagnarGrootKoerkamp/minimizersILP and analysis:github.com/treangenlab/sampling-scheme-analysis
Mechanisms of peptide agonist dissociation and deactivation of adhesion G-protein-coupled receptors
Authors: Joshi Keya , Miao Yinglong
Published: September 2024

Adhesion G protein–coupled receptors (ADGRs) belong to Class B2 of GPCRs and are involved in a wide array of important physiological processes. ADGRs contain a GPCR autoproteolysis-inducing (GAIN) domain that is proximal to the receptor N-terminus and undergoes autoproteolysis during biosynthesis to generate two fragments: the N-terminal fragment (NTF) and C-terminal fragment (CTF). Dissociation of NTF reveals a tethered agonist to activate CTF of ADGRs for G protein signaling. Synthetic peptides that mimic the tethered agonist can also activate the ADGRs. However, mechanisms of peptide agonist dissociation and deactivation of ADGRs remain poorly understood. In this study, we have performed all-atom enhanced sampling simulations using a novel Protein-Protein Interaction-Gaussian accelerated Molecular Dynamics (PPI-GaMD) method on the ADGRG2-IP15 and ADGRG1-P7 complexes. The PPI-GaMD simulations captured dissociation of the IP15 and P7 peptide agonists from their target receptors. We were able to identify important low-energy conformations of ADGRG2 and ADGRG1 in the active, intermediate, and inactive states, as well as exploring different states of the peptide agonists IP15 and P7 during dissociation. Therefore, our PPI-GaMD simulations have revealed dynamic mechanisms of peptide agonist dissociation and deactivation of ADGRG1 and ADGRG2, which will facilitate rational design of peptide regulators of the two receptors and other ADGRs.