bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of altering the invitation package on screening participation among never-screeners in the Flemish population-based cancer screening programs
Authors: Kellen Eliane , Meers Zoi , Pil Lore , Goossens Mathijs C.
Published: January 2024

Background

The total coverage of both the Flemish breast cancer and cervical screening program remain suboptimal, with approximately 63% for both. Of all the women invited to the breast cancer screening program, 14.1% never underwent any type of breast cancer screening (any type of mammogram, ultrasound, or clinical breast examination). For the cervical cancer screening, this proportion of ‘never-screeners’ is 12.1%. We conducted two randomized controlled trials to assess whether various communication and presentation styles in the invitation package, were effective at motivating women who had never participated to attend.

Methods

The study population was limited to never-screeners (women who had never participated in the screening program). The RCT embedded in the breast cancer screening consisted of seven intervention arms and one control arm (all of them included a fixed appointment by letter). The RCT embedded in the cervical cancer screening consisted of three intervention arms and two control arms. In both RCTs, several content and style adaptations were made to the invitation letter, information leaflet, and envelope.

Results

None of the intervention arms in either the breast cancer screening or the cervical cancer screening had a statistically significant impact on the participation rate compared to ‘usual care’ (the regular invitation package used in the screening program).

Conclusion

Sending adapted invitation packages to never-screeners, from the Flemish breast and cervical cancer screening program, does not seem to be effective in increasing the proportion of women screened. Innovative methods are needed to motivate never-screeners to be screened.
Dietary insulin indices and low-carbohydrate diet and the odds of colorectal cancer: a case-control study
Authors: Bahrami Alireza , Parastouei Karim , Taghdir Maryam , Ghadyani Mojtaba
Published: January 2024

Background

Regarding the role of insulin and insulin-inducing dietary factors in some cancers’ etiology, we hypothesized that the risk of colorectal cancer may be lessened by following a lower carbohydrate and insulinogenic diet. Therefore, we performed this study to explore the association between a low-carbohydrate diet and insulin indices and the odds of colorectal cancer.

Method

This hospital-based case-control study was conducted on 150 newly diagnosed colorectal cancer patients and 300 healthy age- and sex-matched hospitalized controls. A valid and reliable food frequency questionnaire was used to calculate the insulin indices and low-carbohydrate diet score. Multivariate logistic regression was used to estimate the association between insulin indices and low-carbohydrate diet and the odds of colorectal cancer.

Result

After adjusting for potential confounders, individuals in the highest tertile of insulin indices had a higher risk of colorectal cancer (ORinsulin index = 3.46; 95% CI, 2.00–5.96; ORinsulin load = 2; 95% CI, 1.17–3.41). No association was found between a low-carbohydrate diet and colorectal cancer (OR = 1.55; 95% CI, 0.85–2.84).

Conclusion

Current results demonstrated that a high insulinemic diet was associated with a higher risk of colorectal cancer.
Role of Sodium-Glucose Co-Transporter-2 Inhibitor During Anthracycline Use: An Updated Review
Authors: Basham Humzala Ali , Keswani Shiwani , Kumar Ashesh , Rahol Rai Saroop Kumar allies , Surkasha FNU , Kumari Aneesha , Malik Jahanzeb
Published: January 2024

The coalescence of anthracycline-induced cardiotoxicity and the evolving role of sodium-glucose co-transporter-2 (SGLT-2) inhibitors in oncology and cardiology has prompted a comprehensive review of their mechanisms, clinical implications, and future directions. Anthracyclines, potent chemotherapeutic agents, have been integral in cancer treatment, yet their potential for cardiac harm necessitates careful monitoring and management. We explore the multifactorial nature of anthracycline-induced cardiotoxicity, encompassing diverse patient populations, cumulative doses, and interplay with other treatments. While advancements in imaging and biomarker assessments aid in early detection, the lack of standardized criteria poses challenges. The emergent role of SGLT-2 inhibitors, initially developed for diabetes management, presents a novel avenue for cardioprotection. Beyond glycemic control, these inhibitors exhibit pleiotropic effects, including enhanced diuresis, anti-inflammatory actions, and modulation of energy sources. Consequently, SGLT-2 inhibitors are being investigated for their potential to mitigate cardiotoxic effects, promising an innovative approach in cardio-oncology. Despite these advancements, limitations in data interpretation and patient-specific considerations persist. The future of anthracycline-induced cardiotoxicity research lies in predictive biomarkers, precision medicine, multidisciplinary collaboration, and tailored treatment regimens. By navigating these challenges and harnessing emerging strategies, we aim to optimize cancer treatment efficacy while safeguarding cardiovascular health, ultimately paving the way for a new era of personalized and comprehensive oncologic care.
Retrospective Evaluation of Cystatin C as a Measure of Renal Function in Pediatric Hematopoietic Stem Cell Transplant Patients Receiving Foscarnet for Cytomegalovirus Reactivation
Authors: Pickett Logan R. , Daukshus Nicole P. , Camacho-Bydume Christine , Mathew Sherry , Mauguen Audrey , Cohen Nina , Cancio Maria
Published: January 2024

Background:

Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option that requires renal dose adjustment. Serum creatinine (SCr)-based estimated glomerular filtration rate (eGFR) equations are used to estimate renal function for patients receiving foscarnet, but cystatin C (cysC) has been shown as a possible alternative. Data examining cysC-based eGFR in this population is sparse. Our primary objective was to evaluate outcomes of patients treated with foscarnet dosed utilizing cysC-based eGFR versus SCr-based eGFR.

Methods:

We analyzed patients on the transplantation and cellular therapies service at Memorial Sloan Kettering Kids from January 2011 to September 2021 who received allogeneic hematopoietic cell transplantation and ≥14 days of foscarnet for CMV infection. Patients with cysC-based eGFR were compared to a historical cohort of patients who only had SCr-based eGFR. Outcomes included time to CMV clearance, death or change in anti-CMV therapy. Cumulative incidence curves and cause-specific hazards model were used for analysis.

Results:

In 61 analyzed patients, no differences were found between the cohorts in cumulative incidence of change in anti-CMV therapy (P = 0.17) or death (P = 0.69). After adjustment for multiple confounders, patients in the SCr cohort seemed to have a higher chance of CMV clearance compared with the cysC cohort, but the difference was not statistically significant (hazard ratio = 2.42, P = 0.089). Patients who received corticosteroids appeared to have lower incidence of CMV clearance (P = 0.056).

Conclusions:

We did not find differences in outcomes when dosing foscarnet using cysC versus SCr for treatment of CMV infection.
The Unneglectable Disease Burden of Otitis Media Among Children in China: A Systematic Review and Meta-analysis
Authors: Lin Wanjing , Wang Biying , Wang Mengzhen , Wang Yujie , Tuerdibieke Yelina , Qian Chen , Zhao Genming , Zhang Tao
Published: January 2024

Background:

Otitis media (OM) is one of the most commonly diagnosed infections among children yet with obscure disease burden.

Methods:

The literature published from 1980 to 2022 was retrieved in PubMed, Ovid-EMBASE, Web of Science, CNKI, Wanfang and VIP. Literature screening, quality assessment and data extraction were conducted by 2 independent reviewers. Heterogeneity and publication bias were detected by I
2, Egger’s and Begg’s tests. The data were pooled using the random-effects model. The number of OM cases was estimated by the multiplied model based on pooled results and the 2020 China census data.

Results:

A total of 28,378 literatures were identified with 67 finally included for data analysis. The OM incidence among children was 7.89% [95% confidence interval (CI): 5.43%–11.33%] and the prevalence of OM was 5.13% (95% CI: 3.49%–7.49%). The most common pathogen of the OM cases was Streptococcus pneumoniae (S. pneumoniae), with a positive rate of 33.52% (95% CI: 26.55%–41.29%). The most common serotypes of S. pneumoniae isolated from OM cases were serotypes 19F, 19A, 6B, 23F and 3, with 85.8% covered by the PCV13. We estimated that there were 8,950,797 (95% CI: 6,080,533–12,928,051) OM cases among under-fives in China in 2020, of which 3,374,451 (95% CI: 1,698,901–6,277,862) cases of OM were caused by S. pneumoniae.

Conclusions:

The burden of OM in China was considerable yet neglected. To date, S. pneumoniae was the most frequently detected bacterial pathogen of OM. Vaccination may be effective to protect young children from OM.
Sense of Coherence as a Mediator Between Functional Status and Health-Related Quality of Life in Patients With Heart Failure
Authors: LEE Hsiao-Ping , HSU Wen-Yu , LIU Yu-Hsuan , CHANG Yue-Cune , CHENG Shu-Meng , CHIANG Hui-Hsun
Published: January 2024

Background

Poor functional status relating to heart failure (HF) negatively affects health-related quality of life (HRQOL). Patients with HF, especially those with New York Heart Association (NYHA) Class III or IV HF, often exhibit poor HRQOL because of physical limitations and HF-related symptoms. Although sense of coherence (SOC) has been reported to be a determinant of HRQOL, its role as a mediator between functional status and HRQOL remains unclear, and few studies have explored the prevalence of HF in patients in NYHA Classes I and II.

Purpose

This study was designed to investigate SOC as a mediator between different functional status classes and HRQOL in patients with HF.

Methods

A cross-sectional study was conducted on patients with HF recruited from a hospital in northern Taiwan from April 2020 to September 2020. The Minnesota Living with Heart Failure Questionnaire and a questionnaire on sociodemographic characteristics; functional classification in terms of NYHA Classes I, II, and III; and SOC were administered. The PROCESS v3.5 (by Andrew F. Hayes) macro was applied to analyze the effects, and Model 4 was used to examine the mediating role of SOC on the relationship between NYHA functional class and HRQOL.

Results

Of the 295 participants, SOC was found to mediate the effects of functional status on HRQOL more significantly in patients in Class II than those in Class III but not more significantly in patients in Class I than those in Class III. A weaker mediating effect of SOC was noted on the relationship between functional status and HRQOL in patients with HF in NYHA Class II than those in Class III.

Conclusions

In patients with HF, poor functional status often reduces HRQOL significantly. SOC mediates the relationship between functional status and HRQOL more significantly in those in NYHA Class II than those in Class III. Nursing staff should work to increase patients' SOC by strengthening their coping capacity and improving their functional status to improve their HRQOL.
Hospital-Level Care at Home for Acutely Ill Adults in Rural Settings
Authors: Desai Meghna P. , Ross Joseph B. , Blitzer Stephanie , Como Natalie , Horton Devin John , Ostergar Jaimi , Hernández Carme , Levine David M.
Published: January 2024

Residents in rural areas face barriers to accessing acute care. Rural home hospital (RHH) or delivery of acute care at home could represent an important clinical care model. This study assessed the feasibility and acceptability of RHH as a substitute to traditional hospital care. Patients were cared for by a remote RHH attending physician and an RHH registered nurse deployed to the home. The study team conducted daily check-ins with RHH clinicians to assess workflows for completion. Surveys assessed patient experience and qualitative interviews assessed perceived acceptability, safety, and quality of care. We completed qualitative analysis of the interviews and coded qualitative data into domains and subdomains through an iterative process. RHH was successfully deployed to three acutely ill patients in rural Utah. RHH admission, daily care, and discharge processes were accomplished for each patient. From qualitative analysis, we identified four domains: (1) Perceived comfort level during RHH admission, (2) Perceived safety during RHH admission, (3) Perceived quality of care during RHH admission, and (4) Perception of RHH workflows. We found acute care was delivered to rural homes with satisfactory patient and clinician experience. Team dynamics, technology build, robust clinical and operational workflows, and care coordination were important to a successful admission. Learnings from this study can inform program design and training for RHH teams and startup for larger RHH evaluation. Home hospital care is expanding rapidly in the United States and RHH could represent an important clinical care model.
Improving outcomes in emergency general surgery: Construct of a collaborative quality initiative
Authors: Hemmila Mark R. , Neiman Pooja U. , Hoppe Beckie L. , Gerhardinger Laura , Kramer Kim A. , Jakubus Jill L. , Mikhail Judy N. , Yang Amanda Y. , Lindsey Hugh J. , Golden Roy J. , Mitchell Eric J. , Scott John W. , Napolitano Lena M.
Published: January 2024

BACKGROUND

Emergency general surgery conditions are common, costly, and highly morbid. The proportion of excess morbidity due to variation in health systems and processes of care is poorly understood. We constructed a collaborative quality initiative for emergency general surgery to investigate the emergency general surgery care provided and guide process improvements.

METHODS

We collected data at 10 hospitals from July 2019 to December 2022. Five cohorts were defined: acute appendicitis, acute gallbladder disease, small bowel obstruction, emergency laparotomy, and overall aggregate. Processes and inpatient outcomes investigated included operative versus nonoperative management, mortality, morbidity (mortality and/or complication), readmissions, and length of stay. Multivariable risk adjustment accounted for variations in demographic, comorbid, anatomic, and disease traits.

RESULTS

Of the 19,956 emergency general surgery patients, 56.8% were female and 82.8% were White, and the mean (SD) age was 53.3 (20.8) years. After accounting for patient and disease factors, the adjusted aggregate mortality rate was 3.5% (95% confidence interval [CI], 3.2–3.7), morbidity rate was 27.6% (95% CI, 27.0–28.3), and the readmission rate was 15.1% (95% CI, 14.6–15.6). Operative management varied between hospitals from 70.9% to 96.9% for acute appendicitis and 19.8% to 79.4% for small bowel obstruction. Significant differences in outcomes between hospitals were observed with high- and low-outlier performers identified after risk adjustment in the overall cohort for mortality, morbidity, and readmissions. The use of a Gastrografin challenge in patients with a small bowel obstruction ranged from 10.7% to 61.4% of patients. In patients who underwent initial nonoperative management of acute cholecystitis, 51.5% had a cholecystostomy tube placed. The cholecystostomy tube placement rate ranged from 23.5% to 62.1% across hospitals.

CONCLUSION

A multihospital emergency general surgery collaborative reveals high morbidity with substantial variability in processes and outcomes among hospitals. A targeted collaborative quality improvement effort can identify outliers in emergency general surgery care and may provide a mechanism to optimize outcomes.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Devosia rhodophyticola sp. nov. and Devosia algicola sp. nov., isolated from a marine red alga
Authors: Kim Jeong Min , Baek Woonhee , Choi Byeong Jun , Bayburt Hülya , Baek Ju Hye , Han Dong Min , Lee Sung Chul , Jeon Che Ok
Published: January 2024

Two Gram-stain-negative, obligately aerobic, motile rod bacteria, designated as G2-5T and G20-9T, exhibiting catalase- and oxidase-positive activities, were isolated from the phycosphere of a Chondrus species, a marine red alga. Strain G2-5T exhibited optimal growth at 30 °C and pH 5.0–6.0 and in the presence of 0.5–1.0% NaCl. In contrast, strain G20-9T demonstrated optimal growth at 25 °C and pH 6.0 and in the presence of 0.5–1.5% NaCl. Both strains contained ubiquinone-10, summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c), C18 : 0 and 11-methyl-C18 : 1
 ω7c, and diphosphatidylglycerol and phosphatidylglycerol as the major respiratory isoprenoid quinone, cellular fatty acids and polar lipids, respectively. The genomic DNA G+C contents were 57.2 mol% for strain G2-5T and 57.5 mol% for strain G20-9T. Strains G2-5T and G20-9T exhibited 98.2 % 16S rRNA gene sequence similarity, along with 82.3 % average nucleotide identity (ANI) and 25.0 % digital DNA–DNA hybridization (dDDH) values, indicating that they represent different species. Phylogenetic analyses based on both 16S rRNA gene and genome sequences revealed that strains G2-5T and G20-9T formed distinct phylogenic lineages within the genus

Devosia

. Strains G2-5T and G20-9T were most closely related to

Devosia limi

DSM 17137T and

Devosia beringensis

S02T with 97.7 and 96.9 % 16S rRNA gene sequence similarities, respectively. The ANI and dDDH values between strains G2-5T and G20-9T and other

Devosia

species were lower than 73.9 and 19.2 %, respectively, suggesting that they constitute novel species within the genus

Devosia

. Based on their distinct phenotypic, chemotaxonomic, and molecular characteristics, strains G2-5T and G20-9T represent two novel species of the genus

Devosia

, for which the names Devosia rhodophyticola sp. nov. (G2-5T=KACC 22601T=JCM 35404T) and Devosia algicola sp. nov. (G20-9T=KACC 22650T=JCM 35405T) are proposed, respectively.
Multiple independent losses of sporulation and peptidoglycan in the Mycoplasmatales and related orders of the class Bacilli
Authors: Field Christian J. , Bowerman Kate L. , Hugenholtz Philip
Published: January 2024

Many peptidoglycan-deficient bacteria such as the

Mycoplasmatales

are known host-associated lineages, lacking the environmental resistance mechanisms and metabolic capabilities necessary for a free-living lifestyle. Several peptidoglycan-deficient and non-sporulating orders of interest are thought to be descended from Gram-positive sporulating

Bacilli

through reductive evolution. Here we annotate 2650 genomes belonging to the class

Bacilli

, according to the Genome Taxonomy Database, to predict the peptidoglycan and sporulation phenotypes of three novel orders, RFN20, RF39 and ML615J-28, known only through environmental sequence surveys. These lineages are interspersed between peptidoglycan-deficient non-sporulating orders including the

Mycoplasmatales

and

Acholeplasmatales

, and more typical Gram-positive orders such as the

Erysipelotrichales

and Staphylococcales. We use the extant genotypes to perform ancestral state reconstructions. The novel orders are predicted to have small genomes with minimal metabolic capabilities and to comprise a mix of peptidoglycan-deficient and/or non-sporulating species. In contrast to expectations based on cultured representatives, the order

Erysipelotrichales

lacks many of the genes involved in peptidoglycan and endospore formation. The reconstructed evolutionary history of these traits suggests multiple independent whole-genome reductions and loss of phenotype via intermediate transition states that continue into the present. We suggest that the evolutionary history of the reduced-genome lineages within the class

Bacilli

is one driven by multiple independent transitions to host-associated lifestyles, with the degree of reduction in environmental resistance and metabolic capabilities correlated with degree of host association.
Pharmacogenomic discovery of genetically targeted cancer therapies optimized against clinical outcomes
Authors: Truesdell Peter , Chang Jessica , Villa Doris Coto , Dai Meiou , Zhao Yulei , McIlwain Robin , Young Stephanie , Hiley Shawna , Craig Andrew W. , Babak Tomas
Published: January 2024

Despite the clinical success of dozens of genetically targeted cancer therapies, the vast majority of patients with tumors caused by loss-of-function (LoF) mutations do not have access to these treatments. This is primarily due to the challenge of developing a drug that treats a disease caused by the absence of a protein target. The success of PARP inhibitors has solidified synthetic lethality (SL) as a means to overcome this obstacle. Recent mapping of SL networks using pooled CRISPR-Cas9 screens is a promising approach for expanding this concept to treating cancers driven by additional LoF drivers. In practice, however, translating signals from cell lines, where these screens are typically conducted, to patient outcomes remains a challenge. We developed a pharmacogemic (PGx) approach called “Clinically Optimized Driver Associated PGx” (CODA-PGx) that accurately predicts genetically targeted therapies with clinical-stage efficacy in specific LoF driver contexts. Using approved targeted therapies and cancer drugs with available real-world evidence and molecular data from hundreds of patients, we discovered and optimized the key screening principles predictive of efficacy and overall patient survival. In addition to establishing basic technical conventions, such as drug concentration and screening kinetics, we found that replicating the driver perturbation in the right context, as well as selecting patients where those drivers are genuine founder mutations, were key to accurate translation. We used CODA-PGX to screen a diverse collection of clinical stage drugs and report dozens of novel LoF genetically targeted opportunities; many validated in xenografts and by real-world evidence. Notable examples include treating STAG2-mutant tumors with Carboplatin, SMARCB1-mutant tumors with Oxaliplatin, and TP53BP1-mutant tumors with Etoposide or Bleomycin.

One Sentence Summary

We identified principles of pharmacogenomic screening that predict clinical efficacy in cancer patients with specific driver mutations.
Protecting Allogeneic Pancreatic Islet Grafts by Engineered Veto
Authors: Qi Yan , Zhang Xianghua , Konigsberg Paula , Cull Janae , McCoy Patrick , Cruz Coral , Dahl Kevin , Staerz Uwe
Published: January 2024

In today’s clinical practice, general immune suppression regimens are used to prevent transplant rejection. Though highly effective, they impair a patient’s protection against infectious challenges. Strategies are being sought that prevent graft rejection without inhibiting beneficial immune functions. One such approach is based on the classical veto effect that employs donor-derived CD8+T cells to inhibit cellular immune responses. Yet, allogeneic grafts may only be partially protected by classical veto as CD8+T cells may fail to remove organ-specific alloreactive T cells. To induce transplant specific immune unresponsiveness, if not tolerance, it may be necessary to endow grafted tissues with veto. Adenoviral vectors were designed that expressed the CD8 α-chain as transgene and thus conferred the immune inhibitory veto function to cells of grafted tissues. In the present model, adenoviral vector vectors protected transduced allogeneic pancreatic islets from rejection in fully immune competent recipients. These studies demonstrated that a tissue-engineering approached could be used to create universally acceptable transplants.
Effect of Artificial Lung Fiber Bundle Geometric Design on Micro- and Macro-scale Clot Formation
Authors: Lai Angela , Omori Natsuha , Napolitano Julia E. , Antaki James F. , Cook Keith E.
Published: January 2024

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen and carbon dioxide to and from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow range of parameters that determine gas exchange efficiency and blood flow resistance, such as fiber packing density, path length, and frontal area. However, these parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3-D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro-rods (380 micron diameter) arranged with varying packing densities (40, 50, and 60%) and path lengths (2 and 4 cm). Blood was pumped through the device corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of fiber bundle enhances deposition upstream, and consequently (3) greater path length provides more clot-free fiber surface area for gas exchange than a shorter path length. These results can be used to create less thrombogenic, more efficient artificial lung designs.

Translational Impact Sentence

Fiber bundle parameters, such as decreased packing density, increased blood flow velocity, and a longer path length, can be used to design a less thrombogenic, more efficient artificial lung to extend functionality.
Development and validation of a subject-specific integrated finite element musculoskeletal model of human trunk with ergonomic and clinical applications
Authors: Ghezelbash Farshid , Eskandari Amir Hossein , Shirazi-Adl Aboulfazl , Larivière Christian
Published: January 2024

Background and Objectives

Biomechanical modeling of the human trunk is crucial for understanding spinal mechanics and its role in ergonomics and clinical interventions. Traditional models have been limited by only considering the passive structures of the spine in finite element (FE) models or incorporating active muscular components in multi-body musculoskeletal (MS) models with an oversimplified spine. This study aimed to develop and validate a subject-specific coupled FE-MS model of the trunk that integrates detailed representation of both the passive and active components for biomechanical simulations.

Methods

We constructed a parametric FE model of the trunk, incorporating a realistic muscle architecture, personalized through imaging datasets and statistical shape models. To validate the model, we compared tissue-level responses with in vitro experiments, and muscle activities and intradiscal pressures versus in vivo measurements during various physical activities. We further demonstrated the versatility of the proposed personalized integrated framework through additional applications in ergonomics (i.e., wearing an exoskeleton) and surgical interventions (e.g., nucleotomy and spinal fusion).

Results

The model demonstrated satisfactory agreement with experimental data, showcasing its validity to predict tissue- and disc-level responses accurately, as well as muscle activity and intradiscal pressures. When simulating ergonomics scenarios, the exoskeleton-wearing condition resulted in lower intradiscal pressures (1.9 MPa vs. 2.2 MPa at L4-L5) and peak von Mises stresses in the annulus fibrosus (2.2 MPa vs. 2.9 MPa) during forward flexion. In the context of surgical interventions, spinal fusion at L4-L5 led to increased intradiscal pressure in the adjacent upper disc (1.72 MPa vs. 1.58 MPa), whereas nucleotomy minimally influenced intact disc pressures but significantly altered facet joint loads and annulus fibrosus radial strains.

Conclusions

The integrated FE-MS model of the trunk represents a significant advancement in biomechanical simulations, providing insights into the intricate interplay between active and passive spinal components. Its predictive capability extends beyond that of conventional models, enabling detailed risk analysis and the simulation of varied surgical outcomes. This comprehensive tool has potential implications for the design of ergonomic interventions and the optimization of surgical techniques to minimize detrimental effects on spinal mechanics.
A universal molecular mechanism driving aging
Authors: Jin Wan , Zheng Jing , Xiao Yu , Ju Lingao , Chen Fangjin , Fu Jie , Jiang Hui , Zhang Yi
Published: January 2024

How cell replication ultimately results in aging and the Hayflick limit are not fully understood. Here we show that clock-like accumulation of DNA G-quadruplexes (G4s) throughout cell replication drives conserved aging mechanisms. G4 stimulates transcription-replication interactions to delay genome replication and impairs DNA re-methylation and histone modification recovery, leading to loss of heterochromatin. This creates a more permissive local environment for G4 formation in subsequent generations. As a result, G4s gradually accumulate on promoters throughout mitosis, driving clock-like DNA hypomethylation and chromatin opening. In patients andin vitromodels, loss-of-function mutations in the G4-resolving enzymes WRN, BLM and ERCC8 accelerate the erosion of the epigenomic landscape around G4. G4-driven epigenomic aging is strongly correlated with biological age and is conserved in yeast, nematodes, insects, fish, rodents, and humans. Our results revealed a universal molecular mechanism of aging and provided mechanistic insight into how G-quadruplex processor mutations drive premature aging.
Shaping up genomes: Prokaryotic roots and eukaryotic diversification of SMC complexes
Authors: van Hooff Jolien J.E. , Raas Maximilian W.D. , Tromer Eelco C. , Eme Laura
Published: January 2024

Across the tree of life, SMC complexes organize, segregate and regulate DNA. In contrast to prokaryotes, which often possess one SMC complex, eukaryotes usually have four such complexes. This expanded set is involved in managing the considerably larger nuclear genomes of eukaryotes, which are distributed across multiple chromosomes. Despite their essential functions, SMC complexes exhibit variations across model eukaryotes, suggesting an even greater variety of these complexes that remains unexplored. Here, we aimed to uncover the diversity and evolution of SMC complexes across eukaryotes, and their deeper, prokaryotic evolutionary origins. For this, we conducted in-depth comparative genomic and phylogenetic analyses of SMC complexes. We show that the last eukaryotic common ancestor (LECA) likely had fully-fledged versions of all four complexes and that the condensin II complex was later lost at least 30 times in eukaryotes. We report evidence that proteins previously designated as functional analogs in various model organisms (e.g., Sororin, Securin, Nse5 and Nse6) are in fact genuine orthologs. Finally, we traced the prokaryotic origins of these complexes and propose that a single SMC complex duplicated in an early archaeon. Altogether, we provide a comprehensive overview of eukaryotic SMC complex diversity and evolution, both addressing and generating questions about their functioning in ancestral and contemporary organisms.
Reprogramming neuroblastoma by diet-enhanced polyamine depletion
Authors: Cherkaoui Sarah , Yang Lifeng , McBride Matthew , Turn Christina S. , Lu Wenyun , Eigenmann Caroline , Allen George E. , Panasenko Olesya O. , Zhang Lu , Vu Annette , Liu Kangning , Li Yimei , Gandhi Om H. , Surrey Lea , Wierer Michael , White Eileen , Rabinowitz Joshua D. , Hogarty Michael D. , Morscher Raphael J.
Published: January 2024

Neuroblastoma is a highly lethal childhood tumor derived from differentiation-arrested neural crest cells1,2. Like all cancers, its growth is fueled by metabolites obtained from either circulation or local biosynthesis3,4. Neuroblastomas depend on local polyamine biosynthesis, with the inhibitor difluoromethylornithine showing clinical activity5. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumor differentiation, and profound survival gains in the TH-MYCNmouse model. Specifically, an arginine/proline-free diet decreases the polyamine precursor ornithine and augments tumor polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at adenosine-ending codons. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by the diet-drug combination, favors a pro-differentiation proteome. These results suggest that the genes of specific cellular programs have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of pediatric cancers.

Graphical Abstract

Highlights

- Extra-tumoral conversion of arginine feeds tumor ornithine via uptake from circulation in MYCN-neuroblastoma.

- A proline and arginine free diet enhances pharmacological polyamine depletion via reduced ornithine substrate availability.

- Polyamine depletion disrupts oncogenic translation to induce a pro-differentiation proteome causing neuroblast differentiation and prolonged survival in the TH-MYCN mouse model.

- Genes of specific cellular programs have evolved codon usage preferences that enable coherent translational rewiring in response to metabolic stress, such as polyamine depletion.
Chromosome-scale genome assembly ofCamellia crapnellianaprovides insights into the fatty acid biosynthesis
Authors: Zhang Fen , Feng Li-ying , Lin Pei-fan , Jia Ju-jin , Gao Li-zhi
Published: January 2024

Camellia crapnellianaTutch., belonging to the Theaceae family, is an excellent landscape tree species with high ornamental value. It is particularly an important woody oil-bearing plant with high ecological, economic, and medicinal values. Here, we first report the chromosome-scale reference genome ofC. crapnellianawith integrated technologies of SMRT, Hi-C and Illumina sequencing platforms. The genome assembly had a total length of ∼2.94 Gb with contig N50 of ∼67.5 Mb, and ∼96.34% of contigs were assigned to 15 chromosomes. In total, we predicted 37,390 protein-coding genes, ∼99.00% of which were functionally annotated. Comparative genomic analysis showed that theC. crapnellianagenome underwent a whole-genome duplication event shared across theCamelliaspecies and an γ -WGT event that was shared by all core eudicot plants. Furthermore, we identified the major genes involved in the biosynthesis of oleic acids and terpenoids inC. crapnelliana. The chromosome-scale genome ofC. crapnellianawill become valuable resources for understanding the genetic basis of the fatty acid biosynthesis, and greatly facilitate the exploration and conservation ofC. crapnelliana.
Protein deuteration via algal amino acids to overcome proton back-exchange for fast-MAS solid-state NMR of large proteins
Authors: Aucharova Hanna , Klein Alexander , Gomez Sara Medina , Söldner Benedikt , Vasa Suresh K. , Linser Rasmus
Published: January 2024

With perdeuteration, a current standard for solid-state NMR spectroscopy, large proteins suffer from incomplete amide-proton back-exchange. Using a 72 kDa micro-crystalline protein, we show that deuteration exclusively via deuterated amino acids, largely suppressing sidechain protonation, provides spectral resolution comparable to perdeuterated preparations at intermediate spinning frequencies without proton back-exchange obstacles.
The conserved σDstress response monitors multiple aspects of envelope integrity in corynebacteria
Authors: Hart Elizabeth M. , Lyerly Evan , Bernhardt Thomas G.
Published: January 2024

The cell envelope fortifies bacterial cells against antibiotics and other insults. Species in theMycobacterialesorder have a complex envelope that includes an outer layer of mycolic acids called the mycomembrane (MM) and a cell wall composed of peptidoglycan and arabinogalactan. This envelope architecture is unique among bacteria and contributes significantly to the virulence of pathogenicMycobacterialeslikeMycobacterium tuberculosis. Characterization of pathways that govern envelope biogenesis in these organisms is therefore critical in understanding their biology and for identifying new antibiotic targets. To better understand MM biogenesis, we developed a cell sorting-based screen for mutants defective in the surface exposure of a porin normally embedded in the MM of the model organismCorynebacterium glutamicum.The results revealed a requirement for the conserved σDenvelope stress response in porin export and identified MarPas the site-1 protease, respectively, that activate the response by cleaving the membrane-embedded anti-sigma factor. A reporter system revealed that the σDpathway responds to defects in mycolic acid and arabinogalactan biosynthesis, suggesting that the stress response has the unusual property of being induced by activating signals that arise from defects in the assembly of two distinct envelope layers. Our results thus provide new insights into howC. glutamicumand related bacteria monitor envelope integrity and suggest a potential role for members of the σDregulon in protein export to the MM.

AUTHOR SUMMARY

Bacteria within theMycobacterialesorder, which includes the pathogenMycobacterium tuberculosis,have a unique multilayered cell surface architecture. How they sense and respond to defects in the construction of this distinct envelope to maintain homeostasis remains poorly understood. Here, we used the model organismCorynebacterium glutamicumto reveal that the conserved σDenvelope stress response pathway responds to two distinct signals resulting from defects in different envelope layers. The results provide new insight into how members of theMycobacterialesmonitor the integrity of their surface and pave the way for the identification of novel vulnerabilities in envelope biogenesis that may be useful for targeting with antibiotics.
“Ca. Nitrosocosmicus” members are the dominant archaea associated with pepper (Capsicum annuumL.) and ginseng (Panax ginsengC.A. Mey.) plants’ rhizospheres
Authors: Lee Ui-Ju , Gwak Joo-Han , Choi Seungyeon , Jung Man-Young , Lee Tae Kwon , Ryu Hojin , Awala Samuel Imisi , Wanek Wolfgang , Wagner Michael , Quan Zhe-Xue , Rhee Sung-Keun
Published: January 2024

Background

Although archaea are widespread in terrestrial environments, little is known about the selection forces that shape their composition, functions, survival, and proliferation strategies in the rhizosphere. The ammonia-oxidizing archaea (AOA), which are abundant in soil environments, catalyze the first step of nitrification and have the potential to influence plant growth and development significantly.

Results

Based on archaeal 16S rRNA andamoAgene (encoding the ammonia monooxygenase subunit A) amplicon sequencing analysis, distinct archaeal communities dominated by AOA were found to be associated with the root systems of pepper (Capsicum annuumL.) and ginseng (Panax ginsengC.A. Mey.) plants compared to bulk soil not penetrated by roots. AOA related to “CandidatusNitrosocosmicus”, which, unlike most other AOA, harbor genes encoding manganese catalase (MnKat), dominated rhizosphere soils, and thus contributed to the development of distinct archaeal communities in rhizospheres. Accordingly, for both plant species, the copy number ratios of AOA MnKat genes toamoAgenes were significantly higher in rhizosphere soils than in bulk soils. In contrast to MnKat-negative strains from other AOA clades, the catalase activity of a representative isolate of “Ca.Nitrosocosmicus” was demonstrated. Members of this clade were enriched in H2O2-amended bulk soils, and constitutive expression of their MnKat gene was observed in both bulk and rhizosphere soils.

Conclusions

Due to their abundance, “Ca.Nitrosocosmicus” members can be considered key players mediating the nitrification process in rhizospheres. The selection of this MnKat-containing AOA in rhizospheres of several agriculturally important plants hints at a previously overlooked AOA-plant interaction. For additional mechanistic analyses of the interaction, this key clade of AOA with cultured representatives can be employed.
Fibronectin 1 is a novel biomarker of obstetric antiphospholipid syndrome
Authors: Xu Jinfeng , Chung Tenchi , Hu Zhe , Tian Yuan , Ling Qiao , Wang Xiaodong , Peng Bing
Published: January 2024

Objective

To investigate novel biomarkers and the mechanism of obstetric antiphospholipid syndrome (OAPS).

Methods

HTR8/SVneo cells line were treated with plasma from OAPS (OAPS group) and healthy (NC group) pregnant women, respectively. The changes induced by plasma treatment at the transcriptome level were examined by RNA sequencing of the cells. Results were analyzed with bioinformatics tools to elucidate the potential biomarkers. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, hematoxylin and eosin (HE), immunohistochemistry (IHC), and immunofluorescence (IF) were used for subsequent validation.

Results

Bioinformatic analysis revealed the expression of Fibronectin 1 (FN1) was significantly increased in OAPS group. On analyzing molecular function, OAPS plasma exposure mainly affected the expression of the genes related to extracellular matrix (ECM) structural constituent. Compared to the NC group, differently expressed genes were mainly annotated to the collagen-containing ECM matrix and the ECM organization. In OAPS group, the protein expression of FN1 was also increased in blood (p<0 .05). The mRNA and protein expression of FN1 in placenta tissue were increased (p<0 .05) in OAPS group. Massive degeneration and atrophy can be seen in placental villi, with a significant reduction or disappearance of syncytiotrophoblasts and excessive fibrinoid deposition in the villous stroma of OAPS placenta. Both IHC and IF results showed the staining area and intensity of FN1 in the placental villi and stroma were significantly higher in OAPS group.

Conclusions

FN1 may play a potential role in the pathogenic mechanisms of OAPS.

Highlights
Role of isotopes in microturbulence from linear to saturated Ohmic confinement regimes
Authors: Qi Lei , Kwon Jae-Min , Hahm T. S. , Leconte M. , Yi Sumin , Cho Y. W. , Seo Janghoon
Published: January 2024

The first-principle gyrokinetic numerical experiments investigating the isotopic dependence of energy confinement achieve a quantitative agreement with experimental empirical scalings, particularly in Ohmic and L-mode tokamak plasmas. Mitigation of turbulence radial electric field intensity |δEr|2 and associated poloidal δE×B fluctuating velocity with the radial correlation length lcr∝Mi0.11 strongly deviating from the gyro-Bohm scaling is identified as the principal mechanism behind the isotope effects. Three primary contributors are classified: the deviation from gyro-Bohm scaling, zonal flow, and trapped electron turbulence stabilization. Zonal flow enhances isotope effects primarily through reinforcing the inverse dependence of turbulence decorrelation rate on isotope mass with ωc∝Mi−0.76, which markedly differs from the characteristic linear frequency. The findings offer insights into isotope effects, providing critical implications for energy confinement optimization in tokamak plasmas.

Published by the American Physical Society
2024
Inductive and Capacitive Hysteresis of Current-Voltage Curves: Unified Structural Dynamics in Solar Energy Devices, Memristors, Ionic Transistors, and Bioelectronics
Authors: Bisquert Juan
Published: January 2024

Hysteresis observed in the current-voltage curves of both electronic and ionic devices is a phenomenon where the curve's shape is altered on the basis of the measurement speed. This effect is driven by internal processes that introduce a time delay in the response to an external stimulus, leading to measurements being dependent on the history of the past disturbances. This hysteresis effect has posed challenges, particularly in solution-processed photovoltaic devices such as halide perovskite solar cells, where it significantly complicates the evaluation of performance quality. In other devices, such as memristors and organic electrochemical transistors for neuromorphic applications, hysteresis is an inherent aspect of their functionality, facilitating transitions between different conductivity states. Natural and artificial ionically conducting channels also exhibit pronounced hysteresis, a crucial component for generating action potentials in neurons. In this study, we aim to categorize various forms of hysteresis by identifying shared elements among diverse physical, chemical, and biological conducting systems. Our method involves examining hysteresis from multiple angles, using simplified models that capture essential response types. We analyze system behavior using techniques such as linear sweep voltammetry and impedance spectroscopy and transient currents resulting from small voltage steps. Our investigation reveals two primary hysteresis types based on how current responds to rapid sweep rates: capacitive hysteresis and inductive hysteresis. These terms correspond to the dominant component in the equivalent circuit, determining the transient time response. Remarkably, these concepts provide insights into vastly different systems, spanning solar cells, capacitors, transistors, electrofluidic nanopores, and protein ion channels. The consistency in electrical responses across the different cases enables the identification of the primary cause of hysteresis. We also elucidate the frequency dependence of hysteresis and the stepwise responses of solar cells, illustrating how fundamental relaxations contribute to the overall surplus or deficit of current during extensive voltage sweeps that define the current-voltage curve.

Published by the American Physical Society
2024
Employees' perceptions of responsible leadership in private security: a mediation model
Authors: Üzüm Burcu , Özkan Osman Seray , Huertas-Valdivia Irene
Published: January 2024

Purpose

A quantitative study sought to better understand responsible leadership (RL) style in the private security sector. The authors analyzed RL’s mediating role in the relationship between rules climate (RC) and employees' perceived organizational support (POS).

Design/methodology/approach

The data were collected through an online questionnaire administered to full-time private guards in Ankara (Turkey). A mediation model was proposed, and research hypotheses were tested with structural equation modeling (SEM).

Findings

The results indicate a significant positive relationship between the company’s RC and managers' RL, and a positive significant relationship between managers' RL and employees' POS. RL mediates the relationship between company’s RC and employees' POS.

Research limitations/implications

The theoretical framework draws on conservation of resources (COR) theory to consider RL an effective resource. The organization’s RC was a key factor the affecting leader’s responsible behaviors.

Originality/value

This study explores a thriving leadership style, gaining research attention across fields. To the authors' knowledge, no prior research has studied this leadership style in the security sector. The authors use COR to increase understanding of an important antecedent (company’s RC) and consequence (employees' POS) of RL, highlighting this emerging style’s mediating role.