bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dietary protein level on intestinal function and inflammation in nursery pigs
Authors: Pearce Sarah C , Nisley Mitchell J , Kerr Brian J , Sparks Chris , Gabler Nicholas K
Published: March 2024

High crude protein (CP; 21% to 26%) diets fed during the first 21 to 28 d postweaning are viewed negatively because of a perceived increase in the incidence rates of diarrhea due to increased intestinal protein fermentation and/or augmented enteric pathogen burden. This is thought to antagonize nursery pig health and growth performance. Therefore, our objective was to evaluate the impact of low vs. high dietary CP on 21-day postweaned pig intestinal function. Analyzed parameters included ex vivo intestinal barrier integrity (ileum and colon), ileal nutrient transport, tissue inflammation, and fecal DM. One hundred and twenty gilts and barrows (average body weight) were randomly assigned to one of two diets postweaning. Diets were fed for 21 d, in two phases. Phase 1 diets: low CP (17%) with a 1.4% standardized ileal digestible (SID) Lys (LCP), or high CP (24%) with a 1.4% SID Lysine (HCP). Phase 2: LCP (17%) and a 1.35% SID lysine, or HCP (24%) formulated to a 1.35% SID lysine. Pig growth rates, feed intakes, and fecal consistency did not differ (P > 0.05) due to dietary treatment. Six animals per treatment were euthanized for additional analyses. There were no differences in colonic epithelial barrier function as measured by transepithelial electrical resistance (TER) and fluorescein isothiocyanate (FITC)-dextran transport between treatments (P > 0.05). Interleukins (IL)-1α, IL-1β, IL-1ra, IL-2 IL-4, IL-6, and IL-12 were not different between treatments (P > 0.05). However, IL-8 and IL-18 were higher in HCP- vs. LCP-fed pigs (P < 0.05). There were no differences in fecal dry matter (DM; P > 0.05) between treatments. In the ileum, there was a tendency (P = 0.06) for TER to be higher in HCP-fed pigs, suggesting a more robust barrier. Interestingly, glucose and glutamine transport were decreased in HCP- vs. LCP-fed pigs (P < 0.05). FITC-dextran transport was not different between treatments (P > 0.05). There were also no differences in ileal cytokine concentrations between diets (P > 0.05). Taken together, the data show that low CP does not negatively impact colonic barrier function, fecal DM, or inflammation. In contrast, ileal barrier function and nutrient transport were altered, suggesting a regional effect of diet on overall intestinal function.
Some results for min matrices associated with Chebyshev polynomials
Authors: Yilmaz Fatih , Arpaci Samet , Ertaş Aybüke
Published: March 2024

In the present study, inspired by the studies in the literature, we consider Min matrix and its Hadamard exponential matrix family whose elements are Chebyshev polynomials of the first kind. Afterwards, we examine their various linear algebraic properties and obtain some inequalities. Furthermore, we shed light on the results we obtained to boost the clarity of our paper with the illustrative examples. In addition to all these, we give two MATLAB-R2023a codes that compute the Min matrix and the Hadamard exponential matrix with Chebyshev polynomials of the first kind entries, as well as calculate some matrix norms.
Reconstruction of luminosity function from flux-limited samples
Authors: Lu Rui-Jing , Chen Wen-Hao , Liang Wen-Qiang , Peng Cheng-Feng
Published: March 2024

The properties of the progenitors of gamma-ray bursts and of their environment are encoded in their luminosity function and cosmic formation rate. They are usually recovered from a flux-limited sample based on Lynden-Bell’s $c^{-}$ method. However, this method is based on the assumption that the luminosity is independent of the redshift. Observationally, if correlated, people use non-parametric $\tau$ statistical method to remove this correlation through the transformation, $L^{\prime }=L/g(z)$, where z is the burst redshift, and $g(z)=(1+z)^{k}$ parametrizes the underlying luminosity evolution. However, the application of this method to different observations could result in very different luminosity functions. By the means of Monte Carlo simulation, in this paper, we demonstrate that the origin of an observed correlation, measured by the $\tau$ statistical method, is a complex combination of multiple factors when the underlying data are correlated. Thus, in this case, it is difficult to unbiasedly reconstruct the underlying population distribution from a truncated sample, unless the detailed information of the intrinsic correlation is accurately known in advance. In addition, we argue that an intrinsic correlation between luminosity function and formation rate is unlikely eliminated by a misconfigured transformation, and the $g(z)$, derived from a truncated sample with the $\tau$ statistical method, does not necessarily represent its underlying luminosity evolution.
Swift/UVOT discovery of Swift J221951−484240: a UV luminous ambiguous nuclear transient
Authors: Oates S R , Kuin N P M , Nicholl M , Marshall F , Ridley E , Boutsia K , Breeveld A A , Buckley D A H , Cenko S B , De Pasquale M , Edwards P G , Gromadzki M , Gupta R , Laha S , Morrell N , Orio M , Pandey S B , Page M J , Page K L , Parsotan T , Rau A , Schady P , Stevens J , Brown P J , Evans P A , Gronwall C , Kennea J A , Klingler N J , Siegel M H , Tohuvavohu A , Ambrosi E , Barthelmy S D , Beardmore A P , Bernardini M G , Bonnerot C , Campana S , Caputo R , Ciroi S , Cusumano G , D’Aì A , D’Avanzo P , D’Elia V , Giommi P , Hartmann D H , Krimm H A , Malesani D B , Melandri A , Nousek J A , O’Brien P T , Osborne J P , Pagani C , Palmer D M , Perri M , Racusin J L , Sakamoto T , Sbarufatti B , Schlieder J E , Tagliaferri G , Troja E , Xu D
Published: March 2024

We report the discovery of Swift J221951−484240 (hereafter: J221951), a luminous slow-evolving blue transient that was detected by the Neil Gehrels Swift Observatory Ultraviolet/Optical Telescope (Swift/UVOT) during the follow-up of gravitational wave alert S190930t, to which it is unrelated. Swift/UVOT photometry shows the UV spectral energy distribution of the transient to be well modelled by a slowly shrinking blackbody with an approximately constant temperature of T ∼ 2.5 × 104 K. At a redshift z = 0.5205, J221951 had a peak absolute magnitude of Mu,AB = −23 mag, peak bolometric luminosity $L_{max}=1.1\times 10^{45}~{\rm erg\, s}^{-1}$ and a total radiated energy of E > 2.6 × 1052 erg. The archival Wide-field Infrared Survey Explorer IR photometry shows a slow rise prior to a peak near the discovery date. Spectroscopic UV observations display broad absorption lines in N  v and O  vi, pointing towards an outflow at coronal temperatures. The lack of emission in the higher H α lines, N i and other neutral lines is consistent with a viewing angle close to the plane of the accretion or debris disc. The origin of J221951 cannot be determined with certainty but has properties consistent with a tidal disruption event and the turn-on of an active galactic nucleus.
Deprojection and stellar dynamical modelling of boxy/peanut bars in edge-on discs
Authors: Dattathri Shashank , Valluri Monica , Vasiliev Eugene , Wheeler Vance , Erwin Peter
Published: March 2024

We present a new method to infer the 3D luminosity distributions of edge-on barred galaxies with boxy-peanut/X (BP/X) shaped structures from their 2D surface brightness distributions. Our method relies on forward modelling of newly introduced parametric 3D density distributions for the BP/X bar, disc and other components using an existing image fitting software package (imfit). We validate our method using an N-body simulation of a barred disc galaxy with a moderately strong BP/X shape. For fixed orientation angles, the derived 3D BP/X-shaped density distribution is shown to yield a gravitational potential that is accurate to at least 5 per cent and forces that are accurate to at least 15 per cent, with average errors being $\sim 1.5~{{\ \rm per\ cent}}$ for both. When additional quantities of interest, such as the orientation of the bar to the line of sight, its pattern speed, and the stellar mass-to-light ratio are unknown they can be recovered to high accuracy by providing the parametric density distribution to the Schwarzschild modelling code FORSTAND. We also explore the ability of our models to recover the mass of the central supermassive black hole. This method is the first to be able to accurately recover both the orientation of the bar to the line of sight and its pattern speed when the disc is perfectly edge-on.
Correlated Allele Frequency Changes Reveal Clonal Structure and Selection in Temporal Genetic Data
Authors: Li Yunxiao , Barton John P
Published: March 2024

In evolving populations where the rate of beneficial mutations is large, subpopulations of individuals with competing beneficial mutations can be maintained over long times. Evolution with this kind of clonal structure is commonly observed in a wide range of microbial and viral populations. However, it can be difficult to completely resolve clonal dynamics in data. This is due to limited read lengths in high-throughput sequencing methods, which are often insufficient to directly measure linkage disequilibrium or determine clonal structure. Here, we develop a method to infer clonal structure using correlated allele frequency changes in time-series sequence data. Simulations show that our method recovers true, underlying clonal structures when they are known and accurately estimate linkage disequilibrium. This information can then be combined with other inference methods to improve estimates of the fitness effects of individual mutations. Applications to data suggest novel clonal structures in an E. coli long-term evolution experiment, and yield improved predictions of the effects of mutations on bacterial fitness and antibiotic resistance. Moreover, our method is computationally efficient, requiring orders of magnitude less run time for large data sets than existing methods. Overall, our method provides a powerful tool to infer clonal structures from data sets where only allele frequencies are available, which can also improve downstream analyses.
Stability in Folk Song Transmission
Authors: Janssen Berit , van Kranenburg Peter
Published: March 2024

In folk song traditions, melodies are circulated through transmission. In this process, parts of melodies may change, while other parts remain stable. Stability has been a long-standing point of interest in folk song research: how can stability be quantified, and can we predict which parts of a melody are stable? We review previous research studying stability in folk song melodies, and present two approaches by which we analyze and predict stability in a corpus of 4120 Dutch folk song melodies. This corpus has been categorized into tune families, or groups of closely related variants. Our first approach quantifies stability through pattern matching of folk song phrases within tune families. Our second approach makes use of annotated characteristic motifs in a subset of 360 folk songs. In both approaches, our hypotheses explain between 5% and 10% of the variation, constituting a medium-sized effect.
Chimeric mutations in grapevine ENHANCED DISEASE RESISTANCE1 improve resistance to powdery mildew without growth penalty
Authors: Yu Xue-Na , Guo Ye , Yang Qianling , Yu Haiyan , Lu Meng-Jiao , Zhao Liang , Jin Zhuo-Shuai , Xu Xiang-nan , Feng Jia-Yue , Wen Ying-Qiang
Published: March 2024

Grapevine (Vitis vinifera L.) incurs severe quality degradation and yield loss from powdery mildew, a major fungal disease caused by Erysiphe necator. ENHANCED DISEASE RESISTANCE1 (EDR1), a Raf-like mitogen-activated protein kinase kinase kinase, negatively regulates defense responses against powdery mildew in Arabidopsis (Arabidopsis thaliana). However, little is known about the role of the putatively orthologous EDR1 gene in grapevine. In this study, we obtained grapevine VviEDR1-edited lines using CRISPR/Cas9. Plantlets containing homozygous and bi-allelic indels in VviEDR1 developed leaf lesions shortly after transplanting into the soil and died at the seedling stage. Transgenic plants expressing wild-type VviEDR1 and mutant Vviedr1 alleles as chimera (designated as VviEDR1-chi) developed normally and displayed enhanced resistance to powdery mildew. Interestingly, VviEDR1-chi plants maintained a spatiotemporally distinctive pattern of VviEDR1 mutagenesis: while almost no mutations were detected from terminal buds, ensuring normal function of the apical meristem, mutations occurred in young leaves and increased as leaves matured, resulting in resistance to powdery mildew. Further analysis showed that the resistance observed in VviEDR1-chi plants was associated with callose deposition, increased production of salicylic acid and ethylene, H2O2 production and accumulation, and host cell death. Surprisingly, no growth penalty was observed with VviEDR1-chi plants. Hence, this study demonstrated a role of VviEDR1 in the negative regulation of resistance to powdery mildew in grapevine and provided an avenue for engineering powdery mildew resistance in grapevine.
Distribution of Three Verticillium dahliae Races in Coastal California and Evaluation of Resistance in Lettuce
Authors: Mandal Mihir K. , Koike Steven T. , Tsuchida Cayla , Stanghellini Hanane , Guerrero Jennifer , Sandoya Germán V. , Klosterman Steven J. , Simko Ivan , Subbarao Krishna V.
Published: March 2024

Verticillium wilt, caused by Verticillium dahliae, is one of the most devastating soilborne diseases of lettuce (Lactuca sativa L.). There are three races of V. dahliae, and each race has been characterized by markers representing race-specific effectors. Race 1 is differentiated by the presence of the functional secretory Ave1 effector. Similarly, races 2 and 3 are differentiated by effectors VdR2e and VdR3e, respectively. Although the presence of race 1 in coastal California was well established, the presence of effector-based races 2 and 3 was uncertain. This study therefore focused on characterizing 727 isolates collected from 142 ranches of symptomatic lettuce and other crops from coastal California. Based on this evaluation, 523 isolates were designated as race 1, 20 isolates as race 2, 23 isolates as race 3, and 17 as race undefined. Isolates representing other Verticillium species totaled 110, and 34 were non-Verticillium fungal species. Because the use of resistant cultivars is a key strategy to manage this disease, we evaluated 48 lettuce germplasm lines and 1 endive (Cichorium endivia L.) line, comprising commercial cultivars and breeding lines, including the race 1–resistant heirloom cultivar La Brillante and the susceptible cultivar Salinas as controls. Resistance against races 1, 2, and 3 along with VdLs17, a virulent isolate of V. dahliae from lettuce that is currently not assigned to a race, was evaluated in replicated greenhouse experiments. Two crisphead lettuce lines, HL28 and HL29, exhibited resistance against race 1 and a partial resistance against race 2, whereas all other lines were highly susceptible to races 1 and 2 and VdLs17. The majority of lines exhibited higher resistance to race 3 relative to the other two races. This study documents the current distribution of the different races in coastal California. In addition, the sources of resistance currently being developed should be effective or partially effective against these races for targeted deployment as soon as they are available.
Preventing Surgical Site Infections in Geriatric Ankle Fracture Surgery with Closed-Incision Vacuum Therapy: A Pilot Study
Authors: van de Voort Jan C. , Brekelmans Wouter , Ritchie Ewan D. , Leijnen Michiel
Published: March 2024

Background

Ankle fractures are among the most common fractures in older adult patients that need surgical treatment. The risk of surgical site infections (SSIs) after ankle fracture surgery ranges between 0.5% and 30%; SSI incidence is higher among older adults. Further, SSIs have significant consequences for subjective functional outcomes and create a need for prolonged intravenous antibiotic therapy and wound care. Accordingly, it is critical to determine risk factors for and establish optimal postoperative wound care to prevent SSIs.

Objective

The aim of the pilot study was to examine the feasibility of closed-incision vacuum therapy (CIVT) to reduce rates of SSI in older adults.

Methods

The authors performed a pilot study of a CIVT system in a population of 10 older adult patients after ankle fracture surgery.

Results

Nine patients experienced uncomplicated wound healing of the lateral incision. One patient (10%) developed an SSI after premature removal of the vacuum system because of technical failure. Six weeks postoperation, overall satisfaction with the CIVT was high; none of the participants complained of incapacitating discomfort or disruptive limitations in postsurgical recovery.

Conclusions

The authors conclude that CIVT is a feasible, safe, and generally well-tolerated therapy to prevent SSIs in postoperative wound healing after open reduction and internal fixation in older adult patients after ankle fracture.
Preoperative Fascia Iliaca Blocks Associated with Decreased Opioid Consumption in Femoral Shaft and Distal Femur Fractures
Authors: Kolodychuk Nicholas , Dubé Michael , DiNicola Nicholas
Published: March 2024

Objectives:

To examine the impact of fascia iliaca (FI) blocks performed in the emergency department on femoral shaft and distal femur fracture patients on opioid consumption, length of stay, and readmission rate.

Methods:

Design:

Prospective cohort study

Setting:

Community-based level 1 trauma center

Patient Selection Criteria:

Patients with isolated low energy femoral shaft or distal femur fractures (OTA/AO 32 and 33) presenting from January 1, 2020 to May 31, 2022 were included.

Outcome Measures and Comparisons:

Opioid consumption, length of stay, discharge disposition, and 30-day readmission rate were compared between patients undergoing fascia iliaca compartment block and not receiving the block.

Results:

136 patients were included. Twenty-four received fascia iliaca block. Both cohorts were primarily female gender 66.7% and 66.9%, respectively for the FI block and no FI block cohort. The majority of the FI block cohort (62.5%) had femoral shaft fractures, while the no FI block cohort had mostly distal femur fractures (56.2%). Mean body mass index, fracture type, and surgical procedure were similar between patients undergoing FI block and not receiving FI block The FI block group had significantly lower opioid consumption pre-operatively (36.1 vs 55.3 morphine milliequivalents (MMEs), p=0.030), post-operatively (71.7 vs 130.6 MMEs, p=0.041), over total hospital stay (107.9 vs 185.9 MMEs), and mean opioid consumption per day of hospital stay (25.9 vs 48.4 MMEs, p=0.003). There was no significant difference in length of stay (4.9 vs 5.0 days, p=0.900), discharge disposition destination (p=0.200), or 30 day readmissions (12.5% vs 4.5%, p=0.148) between groups.

Conclusions:

Undergoing fascia iliaca block in the emergency department was associated with decreased opioid consumption in patients with femoral shaft or distal femur fractures. There was no associated difference in length of stay, discharge disposition, or 30-day readmissions.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Novel Technologies in Artificial Intelligence and Telemedicine for Glaucoma Screening
Authors: Christopher Mark , Hallaj Shahin , Jiravarnsirikul Anuwat , Baxter Sally L. , Zangwill Linda M.
Published: March 2024

Purpose:

To provide an overview of novel technologies in telemedicine and artificial intelligence (AI) approaches for cost-effective glaucoma screening.

Methods/Results:

A narrative review was performed by summarizing research results, recent developments in glaucoma detection and care, and considerations related to telemedicine and AI in glaucoma screening. Telemedicine and AI approaches provide the opportunity for novel glaucoma screening programs in primary care, optometry, portable, and home-based settings. These approaches offer several advantages for glaucoma screening, including increasing access to care, lowering costs, identifying patients in need of urgent treatment, and enabling timely diagnosis and early intervention. However, challenges remain in implementing these systems, including integration into existing clinical workflows, ensuring equity for patients, and meeting ethical and regulatory requirements. Leveraging recent work towards standardized data acquisition as well as tools and techniques developed for automated diabetic retinopathy screening programs may provide a model for a cost-effective approach to glaucoma screening.

Conclusion:

Leveraging novel technologies and advances in telemedicine and AI-based approaches to glaucoma detection show promise for improving our ability to detect moderate and advanced glaucoma in primary care settings and target higher individuals at high risk for having the disease.
Self-rated health and HIV outcomes among adults with diagnosed HIV — Medical Monitoring Project, United States
Authors: Cholli Preetam A. , Buchacz Kate M. , Harris Norma S. , Crim Stacy M. , Yuan Xin , Tie Yunfeng , Koenig Linda J. , Beer Linda
Published: March 2024

Objective(s):

To evaluate associations between self-rated health (SRH) and care outcomes among United States adults with diagnosed HIV infection.

Design:

We analyzed interview and medical record data collected during June 2020–May 2021 from the Medical Monitoring Project, a complex, nationally representative sample of 3692 people with HIV (PWH). Respondents reported SRH on a 5-point Likert type scale (poor to excellent), which we dichotomized into “good or better” and “poor or fair”. We computed weighted percentages with 95% confidence intervals (CIs) and age-adjusted prevalence ratios (aPRs) to investigate associations between SRH and HIV outcomes and demographic, psychosocial, and behavioral characteristics.

Results:

Nationally, 72% of PWH reported “good or better” SRH. PWH with the following characteristics had a lower prevalence of “good or better” SRH, compared with those without: any missed HIV care appointment in the last 12 months (aPR 0.86, 95% CI: 0.81–0.91), symptoms of moderate or severe depression (aPR 0.51, 95% CI: 0.43–0.59) and anxiety (aPR 0.60, 95% CI: 0.54–0.68), unstable housing or homelessness (aPR 0.77, 95% CI: 0.71–0.82), and hunger or food insecurity (aPR 0.74, 95% CI: 0.69–0.80), as well as having a mean CD4 count <200 cells/mm3 vs. CD4+ >500 cells/mm3 (aPR 0.70, 95% CI: 0.57–0.86).

Conclusions:

Though SRH is a holistic measure reflective of HIV outcomes, integrated approaches addressing needs beyond physical health are necessary to improve SRH among PWH in the United States. Modifiable factors like mental health, unstable housing or homelessness, and food insecurity warrant further study as potential high-yield targets for clinical and policy interventions to improve SRH among PWH.
Trends Over Time in Recurrence Patterns and Survival Outcomes after Neoadjuvant Therapy and Surgery for Pancreatic Cancer
Authors: Cass Samuel H. , Tzeng Ching-Wei D. , Prakash Laura R. , Maxwell Jessica , Snyder Rebecca A. , Kim Michael P. , Huey Ryan W. , Smaglo Brandon G. , Pant Shubham , Koay Eugene J. , Wolff Robert A. , Lee Jeffery E. , Katz Matthew H. G. , Ikoma Naruhiko
Published: March 2024

Objective:

We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).

Background:

Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival.

Methods:

Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018.

Results:

The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7 mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6 mo; 3-year rate, 7%, 10%, and 20%; P < 0.005).

Conclusions:

We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.
Burn Patients and Mental Health
Authors: Kang-Auger Gabrielle , Borsuk Daniel E. , Low Nancy , Ayoub Aimina , Auger Nathalie , Buteau Stéphane
Published: March 2024

Objective:

To determine the association between burns and hospitalization for mental health disorders up to three decades later.

Summary Background Data:

Burns are associated with pain, disability, and scarring, but the long-term impact on mental health is unclear.

Methods:

We analyzed a cohort of 23,726 burn patients aged ≥10 years who were matched to 223,626 controls from Quebec, Canada, between 1989 and 2022. The main exposure was admission for a burn. We followed patients during 3,642,206 person-years of follow-up to identify future hospitalizations for psychiatric disorders, substance use disorders, and suicide attempts. We estimated adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between burns and subsequent mental health hospitalization using Cox proportional hazards regression.

Results:

Burn patients had 1.76 times greater risk of mental health hospitalization over time (95% CI 1.72-1.81), compared with controls. Associations were present regardless of burn site, but were greatest for burns covering ≥50% of the body (HR 3.29, 95% CI 2.61-4.15), third degree burns (HR 2.04, 95% CI 1.94-2.14), and burns requiring skin grafts (HR 2.00, 95% CI 1.90-2.10). Compared with controls, burn patients had more than two times the risk of hospitalization for eating disorders (HR 3.14, 95% CI 2.50-3.95), psychoactive substance use disorders (HR 2.27, 95% CI 2.17-2.39), and suicide attempts (HR 2.42, 95% CI 2.23-2.62). Risks were particularly elevated within 5 years of the burn, but persisted throughout follow-up.

Conclusions:

Burns are associated with an increased risk of hospitalization for mental health disorders up to 30 years later.
Genetically identical mice express alternative reproductive tactics depending on social conditions in the field
Authors: Zipple Matthew N. , Vogt Caleb C. , Sheehan Michael J.
Published: March 2024

In many species, establishing and maintaining a territory is critical to survival and reproduction, and an animal's ability to do so is strongly influenced by the presence and density of competitors. Here we manipulate social conditions to study the alternative reproductive tactics displayed by genetically identical, age-matched laboratory mice competing for territories under ecologically realistic social environmental conditions. We introduced adult males and females of the laboratory mouse strain C57BL/6J into a large, outdoor field enclosure containing defendable resource zones under one of two social conditions. We first created a low-density social environment, such that the number of available territories exceeded the number of males. After males established stable territories, we introduced a pulse of intruder males and observed the resulting defensive and invasive tactics employed. In response to this change in social environment, males with large territories invested more in patrolling but were less effective at excluding intruder males as compared with males with small territories. Intruding males failed to establish territories and displayed an alternative tactic featuring greater exploration as compared with genetically identical territorial males. Alternative tactics did not lead to equal reproductive success—males that acquired territories experienced greater survival and had greater access to females.
Crystal structure of the ATPase domain of porcine circovirus type 2 Rep protein
Authors: Guan Shuaiyin , Li Zhen , Han Yang , Tian Ang , Zhou Saisai , Chen Huanchun , Peng Guiqing , Song Yunfeng
Published: March 2024

PCV2 belongs to the genus Circovirus in the family Circoviridae, whose genome is replicated by rolling circle replication (RCR). PCV2 Rep is a multifunctional enzyme that performs essential functions at multiple stages of viral replication. Rep is responsible for nicking and ligating single-stranded DNA and unwinding double-stranded DNA (dsDNA). However, the structure and function of the Rep are still poorly understood, which significantly impedes viral replication research. This study successfully resolved the structure of the PCV2 Rep ATPase domain (PRAD) using X-ray crystallography. Homologous structure search revealed that Rep belonged to the superfamily 3 (SF3) helicase, and multiple conserved residues were identified during sequence alignment with SF3 family members. Simultaneously, a hexameric PRAD model was generated for analysing characteristic structures and sites. Mutation of the conserved site and measurement of its activity showed that the hallmark motifs of the SF3 family influenced helicase activity by affecting ATPase activity and β-hairpin just caused the loss of helicase activity. The structural and functional analyses of the PRAD provide valuable insights for future research on PCV2 replication and antiviral strategies.
In vitro and in silico assessment of anti-biofilm and anti-quorum sensing properties of 2,4-Di-tert butylphenol against Acinetobacter baumannii
Authors: Jha Nisha Kumari , Gopu Venkadesaperumal , Sivasankar Chandran , Singh Satya Ranjan , Devi Palanisamy Bruntha , Murali Ayaluru , Shetty Prathapkumar Halady
Published: March 2024

Introduction.
Acinetobacter baumannii is a nosocomial pathogen with a high potential to cause food-borne infections. It is designated as a critical pathogen by the World Health Organization due to its multi-drug resistance and mortalities reported. Biofilm governs major virulence factors, which promotes drug resistance in A. baumannii. Thus, a compound with minimum selection pressure on the pathogen can be helpful to breach biofilm-related virulence.

Hypothesis/Gap Statement. To identify anti-biofilm and anti-virulent metabolites from extracts of wild Mangifera indica (mango) brine pickle bacteria that diminishes pathogenesis and resistance of A. baumannii.

Aim. This study reports anti-biofilm and anti-quorum sensing (QS) efficacy of secondary metabolites from bacterial isolates of fermented food origin.

Method. Cell-free supernatants (CFS) of 13 bacterial isolates from fermented mango brine pickles were screened for their efficiency in inhibiting biofilm formation and GC-MS was used to identify its metabolites. Anti-biofilm metabolite was tested on early and mature biofilms, pellicle formation, extra polymeric substances (EPS), cellular adherence, motility and resistance of A. baumannii. Gene expression and in silico studies were also carried out to validate the compounds efficacy.

Results. CFS of TMP6b identified as Bacillus vallismortis, inhibited biofilm production (83.02 %). Of these, major compound was identified as 2,4-Di-tert-butyl phenol (2,4-DBP). At sub-lethal concentrations, 2,4-DBP disrupted both early and mature biofilm formation. Treatment with 2,4-DBP destructed in situ biofilm formed on glass and plastic. In addition, key virulence traits like pellicle (77.5 %), surfactant (95.3 %), EPS production (3-fold) and cell adherence (65.55 %) reduced significantly. A. baumannii cells treated with 2,4-DBP showed enhanced sensitivity towards antibiotics, oxide radicals and blood cells. Expression of biofilm-concomitant virulence genes like csuA/B, pgaC, pgaA, bap, bfmR, katE and ompA along with QS genes abaI, abaR significantly decreased. The in silico studies further validated the higher binding affinity of 2,4-DBP to the AbaR protein than the cognate ligand molecule.

Conclusion. To our knowledge, this is the first report to demonstrate 2,4- DBP has anti-pathogenic potential alone and with antibiotics by in vitro, and in silico studies against A. baumannii. It also indicates its potential use in therapeutics and bio-preservatives.
High transferability of neutralizing antibodies against SARS-CoV-2 to umbilical cord blood in pregnant women with BNT162b2 XBB.1.5 vaccine - a retrospective cohort study
Authors: Hayashi Takuma , Sano Kenji , Konishi Ikuo
Published: March 2024

Coronavirus disease 2019 (COVID-19), when contracted by pregnant women, can lead to severe respiratory illness, rapid disease progression, and higher rates of intensive care unit admission. COVID-19 infection during pregnancy is associated with an increased risk of preterm delivery, cesarean section, fetal dysfunction, preeclampsia, and perinatal death. Additionally, vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from pregnant women to their fetuses has been observed. While severe infections in neonates and infants are rare, newborns can experience serious consequences from COVID-19, despite their suboptimal humoral immune system protection. The amino acids in the structural proteins of SARS-CoV-2 are subjected to constant mutation. Since around January 2023, COVID-19, caused by infection with omicron-type SARS-CoV-2 variants, has been prevalent globally. Omicron-type SARS-CoV-2 variants can evade the immune response triggered by traditional mRNA-based COVID-19 vaccines, such as BNT162b2. Therefore, vaccination with a vaccine (BNT162b2 XBB.1.5) that can provide protection against omicron-type SARS-CoV-2 variants is recommended. Therefore, we examined the titers of anti-spike glycoprotein of SARS-CoV-2 IgG and IgA in the blood and umbilical cord blood obtained from pregnant women vaccinated with BNT162b2 XBB.1.5. The results showed that anti-spike glycoprotein of SARS-CoV-2 IgG and IgA titers were highest in the blood and cord blood obtained from pregnant women vaccinated with BNT162b2 XBB.1.5 at late gestational age (28-34 weeks). No serious side effects or adverse events caused by vaccination of pregnant women with BNT162b2 XBB.1.5 were observed in either pregnant women or newborns. In the future, to validate our findings, large cohort clinical studies involving numerous pregnant women must be conducted.
Strong heterologous electron sink outcompetes alternative electron transport pathways in photosynthesis
Authors: Hubáček Michal , Wey Laura T. , Kourist Robert , Malihan-Yap Lenny , Nikkanen Lauri , Allahverdiyeva Yagut
Published: March 2024

Improvement of photosynthesis requires a thorough understanding of electron partitioning under both natural and strong electron sink conditions. We applied a wide array of state-of-the-art biophysical and biochemical techniques to thoroughly investigate the fate of photosynthetic electrons in the engineered cyanobacteriumSynechocystissp. PCC 6803, a blueprint for photosynthetic biotechnology, expressing the heterologous gene for ene-reductase, YqjM. This recombinant enzyme catalyses the reduction of an exogenously added substrate into the desired product by utilising photosynthetically produced NAD(P)H, enabling whole-cell biotransformation. Through coupling the biotransformation reaction with biophysical measurements, we demonstrated that the strong artificial electron sink, outcompetes the natural electron valves, the flavodiiron protein-driven Mehler-like reaction, and cyclic electron transport. These results show that ferredoxin-NAD(P)H-oxidoreductase (FNR) is the preferred route for delivering photosynthetic electrons from reduced ferredoxin and the cellular NADPH/NADP+ ratio as a key factor in orchestrating photosynthetic electron flux. These insights are crucial for understanding molecular mechanisms of photosynthetic electron transport and harnessing photosynthesis for sustainable bioproduction by engineering the cellular source/sink balance. Furthermore, we conclude that identifying the bioenergetic bottleneck of a heterologous electron sink is a crucial prerequisite for targeted engineering of photosynthetic biotransformation platforms.

Significance statement

We coupled the photosynthetic and biocatalytic (whole-cell biotransformation) performance of model cyanobacteria. We employed a heterologous NAD(P)H utilising enzyme, as a strong artificial electron sink, allowing us to gain a comprehensive understanding of photosynthetic electron partitioning. We demonstrated that the strong electron sink outcompetes natural electron sinks and cyclic electron transport.
Control of Medical Digital Twins with Artificial Neural Networks
Authors: Böttcher Lucas , Fonseca Luis L. , Laubenbacher Reinhard C.
Published: March 2024

The objective of personalized medicine is to tailor interventions to an individual patient’s unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data collected over time. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations. Instead, they are often multi-scale, stochastic, and hybrid. This poses a challenge to existing model-based control and optimization approaches that cannot be readily applied to such models. Recent advances in automatic differentiation and neural-network control methods hold promise in addressing complex control problems. However, the application of these approaches to biomedical systems is still in its early stages. This work introduces dynamics-informed neural-network controllers as an alternative approach to control of medical digital twins. As a first use case for this method, the focus is on agent-based models, a versatile and increasingly common modeling platform in biomedicine. The effectiveness of the proposed neural-network control method is illustrated and benchmarked against other methods with two widely-used agent-based model types. The relevance of the method introduced here extends beyond medical digital twins to other complex dynamical systems.
Sagittal balance of the spine - lumbar lordosis or lumbosacral lordosis?
Authors: Song Kai , Chi Pengfei , Yang Qiang , Yang Cao , Wang Bing , Li Fangcai , Zhu Zezhang , Li Weishi , Zhang Jianguo , Wang Zheng
Published: March 2024

Objective

To investigate sagittal spinal alignment from the perspective of the overall curvature of the “S” curve of the human spine, and explore the roles of pelvic incidence (PI) and maximal thoracolumbar vertebral tilt(TLmax) in the classification of the sagittal spinal aligment.

Methods

The tilt of the sacral, lumbar, and thoracic vertebrae (from Co1, S5, S4… to C7) were measured. The minimal sacral vertebral tilt(Smin), maximal thoracolumbar vertebral tilt(TLmax), and minimal thoracic vertebral tilt (Tmin) were recorded. The concept of lumbosacral lordosis (LSL) was introduced, and the Ferguson method was utilized to measure sagittal spinal parameters both in anatomical segmentation (Ferguson L1-S2, Ferguson T1-T12) and functional segmentation (Ferguson LSLmax, Ferguson TKmax). The subjects were grouped based on pelvic incidence (PI) and TLmax separately, and the mean and standard deviation of each parameter were calculated. Chi-square tests were conducted for statistical analysis.

Results

1. Based on PI grouping: PI for all subjects was 45.4 ± 9.5° (21.7-86.4°). Group A consisted of 117 subjects with a mean PI of 34.7 ± 4.4°, Group B had 158 subjects with a mean PI of 45.2 ± 2.9°, and Group C included 113 subjects with a mean PI of 56.7 ± 5.8°. No statistically significant differences were found in tilt of S2, L1, T1, TLmax, Tmin, and Ferguson L1-S2, Ferguson T1-T12, and Ferguson TKmax among Groups A, B, and C. 2. Based on TLmax grouping: TLmax for all subjects was 110.5 ± 5.5° (94.4-132.0°). Group A had 91 subjects with a mean TLmax of 104.0 ± 2.3°, Group B comprised 216 subjects with a mean TLmax of 110.2 ± 2.1°, and Group C included 81 subjects with a mean TLmax of 118.6 ± 3.8°. Significant statistical differences were observed in tilt of S2, L1, T1, Smin, TLmax, Tmin, and Ferguson L1-S2, Ferguson T1-T12, Ferguson LSLmax, and Ferguson TKmax among Groups A, B, and C.

Conclusion

There were no differences in the magnitude of LSL and TK among subjects with different PI, indicating that PI does not affect the overall curvature of the “S” curve in the sagittal spinal aligment. In contrast, TLmax effectively distinguishes the overall curvature of the “S” curve.
The Landscape of RAD51D in Chinese Ovarian Cancer Patients: Prevalence, Correlation with HRD Score, and Correlation with Efficacy
Authors: Sun Tianqi , Zhang Mengpei , Xu Xinyun , Liang Yiming , Chen Jinghong , Li Qingli , Zeng Jing , Li Zhe , Dong Yu , Yin Rutie
Published: March 2024

Human genome is continuously threatened by endogenous and exogeneous sources of DNA damage, DNA damage repair (DDR) mechanisms are vital for genome instability and cancer prevention. Homologous recombination repair (HRR) is one of the most important DDR mechanisms because of its high-fidelity. BRCA1/2 have long been the best characterized HRR genes, but other non-BRCA1/2 HRR genes should not be overlooked. In this study, we illustrate that RAD51D is an important non-BRCA1/2 HRR gene in Chinese ovarian cancer patients, from perspectives including prevalence (2.9% patients mutated in RAD51D, 72.7% of RAD51D mutations were bi-allelic loss-of-function [BILOF]), correlation with HRD score (P=0.295 for RAD51D mutation, P=0.087 for RAD51D BILOF), and correlation with efficacy (progression-free survival: HR=0.685 P=0.069 for RAD51D mutation, HR=0.571 P=0.054 for RAD51D BILOF).
A diverse gut virome fromDrosophila melanogaster
Authors: Ansari Mina Hojat , Staubach Fabian , Alacatli Nurper , Obbard Darren J
Published: March 2024

Drosophila melanogasteris not only one of the most important models of antiviral immunity in invertebrates, but is also a powerful model for research of the gut microbiome. Although recent studies have continued to improve our knowledge of the fly gut microbiota, the viral component of the microbiome has remained unexplored. Here we explore the viral component of theDrosophila melanogastergut microbiome using deep metagenomic DNA sequencing. We recovered 3035 phage sequences, resulting in 167 viral Metagenome-Assembled Genomes. The majority of these sequences are potentially novel bacteriophages from the orderCaudovirales, which mainly target major gut bacteria ofD. melanogaster, includingLactobacillus,Acetobacter, andGluconobacter. Our functional annotation and discovery of auxiliary metabolic genes showed that these bacteriophages have the potential to influence microbial metabolism and genetic information processing. We also identified evidence of known fly pathogens Drosophila Kallithea nudivirus, Vesanto bidna-like virus, and Viltain densovirus, some of which were common in our studied populations. Our findings reveal a complex and diverse phage community in theD. melanogastergut microbiome, paving the way to study host-phage related research in the natural microbial communities.
Microbial abundance estimation and metagenomic studies of holcomb creosote superfund site soil sample
Authors: Kishore D.S , Prasantha C.N , Rambabu Majji , Vasudevann Karthick , Dasegowda K.R.
Published: March 2024

The use of genomic sequencing has greatly improved our ability to profile the microbial communities associated with the environment and host. Among the most common applications of metagenomics is assessing microbiome biodiversity. Holcomb Creosote Superfund Site Soil is located in the North Carolina area, 16s metagenomic Sequencing was carried out from the soil of Holcomb Creosote Superfund Site. To describe the taxonomic diversity and functional profiles of this environment, metagenomic DNA sequence was extracted from a metagenomics library generated from the Holcomb Creosote Superfund Site Soil by 16s metagenomic Sequencing. The DNA was shotgun-sequenced using Illumina and analysed using the MG-RAST server. A soil sample from a large metagenomes sequence collection acquired from shotgun sequencing was investigated for Duke University. Overall sequences in the dataset were 1,34,00,509 comprising a total read length of 4,03,05,03,377 base pairs. The categorization of 8 species was based on the analysis of taxonomic data. The metagenome sequence was submitted by Duke University, Alexander McCumber to NCBI database and can be accessed with the SRA accession number SRX8095153. An online metagenome server (MG RAST) using the subsystem database revealed bacteria had the highest diversity profile revealed that the most abundant domain was 92.3% of bacteria, 5.6% of Eukaryota, 0.1 % of viruses, 1.4% of archaea, and 0.6% of unclassified sequences.The most abundant were Firmicutes (20.5%), and Proteobacteria (10.3%) followed by Actinobacteria (18.4%) and Acidobacteria (7.5%). The functional profile showed an abundance of genes related to subsystems (16.9%), carbohydrates (19.5%), cell wall and capsule (6%), miscellaneous (8.8%), protein metabolism (10%), amino acids and derivatives (14.7%), DNA metabolism (3.4%), cofactors, vitamins, prosthetic groups, pigments (9.2%), membrane transport (1.9%), RNA metabolism (4.4%) and fatty acids, lipids, and isoprenoids (3.6%). This dataset is useful in bioprospecting studies with application in biomedical sciences, biotechnology and microbial, population, and applied ecology fields.
Chemotherapy induces myeloid-driven spatial T-cell exhaustion in ovarian cancer
Authors: Launonen Inga-Maria , Erkan Erdogan Pekcan , Niemiec Iga , Junquera Ada , Hincapié-Otero María , Afenteva Daria , Liang Zhihan , Salko Matilda , Szabo Angela , Perez-Villatoro Fernando , Falco Matias M. , Li Yilin , Micoli Giulia , Nagaraj Ashwini , Haltia Ulla-Maija , Kahelin Essi , Oikkonen Jaana , Hynninen Johanna , Virtanen Anni , Nirmal Ajit J. , Vallius Tuulia , Hautaniemi Sampsa , Sorger Peter , Vähärautio Anna , Färkkilä Anniina
Published: March 2024

To uncover the intricate, chemotherapy-induced spatiotemporal remodeling of the tumor microenvironment, we conducted integrative spatial and molecular characterization of 97 high-grade serous ovarian cancer (HGSC) samples collected before and after chemotherapy. Using single-cell and spatial analyses, we identify increasingly versatile immune cell states, which form spatiotemporally dynamic microcommunities at the tumor-stroma interface. We demonstrate that chemotherapy triggers spatial redistribution and exhaustion of CD8+ T cells due to prolonged antigen presentation by macrophages, both within interconnected myeloid networks termed “Myelonets” and at the tumor stroma interface. Single-cell and spatial transcriptomics identifies prominent TIGIT-NECTIN2 ligand-receptor interactions induced by chemotherapy. Using a functional patient-derived immuno-oncology platform, we show that CD8+T-cell activity can be boosted by combining immune checkpoint blockade with chemotherapy. Our discovery of chemotherapy-induced myeloid-driven spatial T-cell exhaustion paves the way for novel immunotherapeutic strategies to unleash CD8+ T-cell-mediated anti-tumor immunity in HGSC.