bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological and molecular mechanisms associated with potato tuber dormancy
Authors: Dogramaci Munevver , Dobry Emily P , Fortini Evandro A , Sarkar Dipayan , Eshel Dani , Campbell Michael A
Published: April 2024

Tuber dormancy is an important physiological trait that impacts post-harvest storage and end-use qualities of potatoes. Overall, dormancy regulation of potato tubers is a complex process driven by genetic as well as environmental factors. Elucidation of the molecular and physiological mechanisms that influence different dormancy stages of tubers has wider potato breeding and industry-relevant implications. Therefore, the primary objective of this review is to present current knowledge of the diversity in tuber dormancy traits among wild relatives of potatoes and discuss how genetic and epigenetic factors contribute to tuber dormancy. Advancements in understanding of key physiological mechanisms involved in tuber dormancy regulation, such as apical dominance, phytohormone metabolism, and oxidative stress responses, are also discussed. This review highlights the impacts of common sprout suppressors on the molecular and physiological mechanisms associated with tuber dormancy and other storage qualities. Collectively, the literature suggests that significant changes in expression of genes associated with the cell cycle, phytohormone metabolism, and oxidative stress response influence initiation, maintenance, and termination of dormancy in potato tubers. Commercial sprout suppressors mainly alter the expression of genes associated with the cell cycle and stress responses and suppress sprout growth rather than prolonging tuber dormancy.
Searching for planet-driven dust spirals in ALMA visibilities
Authors: Stevenson Edward T , Ribas Álvaro , Speedie Jessica , Booth Richard A , Clarke Cathie J
Published: April 2024

Atacama Large Millimetre/submillimetre Array (ALMA) observations of the thermal emission from protoplanetary disc dust have revealed a wealth of substructures that could evidence embedded planets, but planet-driven spirals, one of the more compelling lines of evidence, remain relatively rare. Existing works have focused on detecting these spirals using methods that operate in image space. Here, we explore the planet detection capabilities of fitting planet-driven spirals to disc observations directly in visibility space. We test our method on synthetic ALMA observations of planet-containing model discs for a range of disc/observational parameters, finding it significantly outperforms image residuals in identifying spirals in these observations and is able to identify spirals in regions of the parameter space in which no gaps are detected. These tests suggest that a visibility-space fitting approach warrants further investigation and may be able to find planet-driven spirals in observations that have not yet been found with existing approaches. We also test our method on six discs in the Taurus molecular cloud observed with ALMA at 1.33 mm, but find no evidence for planet-driven spirals. We find that the minimum planet masses necessary to drive detectable spirals range from ≈0.03 to $0.5 \, M_{\text{Jup}}$ over orbital radii of 10–100 au, with planet masses below these thresholds potentially hiding in such disc observations. Conversely, we suggest that planets ≳0.5–1 MJup can likely be ruled out over orbital radii of ≈20–$60 \, \text{au}$ on the grounds that we would have detected them if they were present.
WISDOM Project – XIX. Figures of merit for supermassive black hole mass measurements using molecular gas and/or megamaser kinematics
Authors: Zhang Hengyue , Bureau Martin , Smith Mark D , Cappellari Michele , Davis Timothy A , Dominiak Pandora , Elford Jacob S , Liang Fu-Heng , Ruffa Ilaria , Williams Thomas G
Published: April 2024

The mass (MBH) of a supermassive black hole (SMBH) can be measured using spatially resolved kinematics of the region where the SMBH dominates gravitationally. The most reliable measurements are those that resolve the smallest physical scales around the SMBHs. We consider here three metrics to compare the physical scales probed by kinematic tracers dominated by rotation: the radius of the innermost detected kinematic tracer Rmin normalized by the SMBH’s Schwarzschild radius (RSchw ≡ 2GMBH/c2, where G is the gravitational constant and c the speed of light), sphere-of-influence (SOI) radius ($R_\mathrm{SOI}\equiv GM_\mathrm{BH}/\sigma _\mathrm{e}^2$, where σe is the stellar velocity dispersion within the galaxy’s effective radius), and equality radius [the radius Req at which the SMBH mass equals the enclosed stellar mass, MBH = M*(Req), where M*(R) is the stellar mass enclosed within the radius R]. All metrics lead to analogous simple relations between Rmin and the highest circular velocity probed Vc. Adopting these metrics to compare the SMBH mass measurements using molecular gas kinematics to those using megamaser kinematics, we demonstrate that the best molecular gas measurements resolve material that is physically closer to the SMBHs in terms of RSchw but is slightly farther in terms of RSOI and Req. However, molecular gas observations of nearby galaxies using the most extended configurations of the Atacama Large Millimeter/submillimeter Array can resolve the SOI comparably well and thus enable SMBH mass measurements as precise as the best megamaser measurements.
Electron-capture supernovae in NS + He star systems and the double neutron star systems
Authors: Guo Yun-Lang , Wang Bo , Chen Wen-Cong , Li Xiang-Dong , Ge Hong-Wei , Jiang Long , Han Zhan-Wen
Published: April 2024

Electron-capture-supernovae (EC-SNe) provide an alternative channel for producing neutron stars (NSs). They play an important role in the formation of double NS (DNS) systems and the chemical evolution of galaxies, and contribute to the NS mass distribution in observations. It is generally believed that EC-SNe originate from e-captures on $\rm ^{24}Mg$ and $\rm ^{20}Ne$ in the massive degenerate oxygen–neon (ONe) cores with masses close to the Chandrasekhar limit (MCh). However, the origin of EC-SNe is still uncertain. In this paper, we systematically studied the EC-SNe in NS + He star systems by considering the explosive oxygen burning that may occur in the near-MCh ONe core. We provided the initial parameter spaces for producing EC-SNe in the initial orbital period − initial He star mass (log$P_{\rm orb}^{\rm i}-M_{\rm He}^{\rm i}$) diagram, and found that both $M_{\rm He}^{\rm i}$ and minimum $P_{\rm orb}^{\rm i}$ for EC-SNe increase with metallicity. Then, by considering NS kicks added to the newborn NS, we investigated the properties of the formed DNS systems after the He star companions collapse into NSs, such as the orbital periods, eccentricities, and spin periods of recycle pulsars (Pspin), etc. The results show that most of the observed DNS systems can be produced by NS kicks of $\lesssim$50 km s−1. In addition, we found that NSs could accrete more material if the residual H envelope on the He star companions is considered, which can form the mildly recycled pulsars (Pspin ∼ 20 ms) in DNS systems.
A comprehensive analysis of pneumococcal two-component system regulatory networks
Authors: Pettersen Jens Sivkær , Nielsen Flemming Damgaard , Andreassen Patrick Rosendahl , Møller-Jensen Jakob , Jørgensen Mikkel Girke
Published: April 2024

Two-component systems are key signal-transduction systems that enable bacteria to respond to a wide variety of environmental stimuli. The human pathogen, Streptococcus pneumoniae (pneumococcus) encodes 13 two-component systems and a single orphan response regulator, most of which are significant for pneumococcal pathogenicity. Mapping the regulatory networks governed by these systems is key to understand pneumococcal host adaptation. Here we employ a novel bioinformatic approach to predict the regulons of each two-component system based on publicly available whole-genome sequencing data. By employing pangenome-wide association studies (panGWAS) to predict genotype-genotype associations for each two-component system, we predicted regulon genes of 11 of the pneumococcal two-component systems. Through validation via next-generation RNA-sequencing on response regulator overexpression mutants, several top candidate genes predicted by the panGWAS analysis were confirmed as regulon genes. The present study presents novel details on multiple pneumococcal two-component systems, including an expansion of regulons, identification of candidate response regulator binding motifs, and identification of candidate response regulator-regulated small non-coding RNAs. We also demonstrate a use for panGWAS as a complementary tool in target gene identification via identification of genotype-to-genotype links. Expanding our knowledge on two-component systems in pathogens is crucial to understanding how these bacteria sense and respond to their host environment, which could prove useful in future drug development.
Association between pro-inflammatory diet and abdominal pain: cross-sectional and case-control study from UK biobank and NHANES 2017–2020
Authors: Li Laifu , Zhuang Yan , Ran Yan , Chen Jiamiao , Wang Lianli , Lu Shiwei , Sun Yating , Ye Fangchen , Dai Fei
Published: April 2024

Background

There is a close association between diet and abdominal pain; however, relationship between inflammatory diet and characteristics of abdominal pain has not been characterized yet.

Methods

This study analyzed baseline data from the UK Biobank, 3-item DHQ-Abdominal Pain Questionnaire (DHQ-3Q), which including abdominal pain in the past 3 months, severity of abdominal pain, and frequency of abdominal pain, and data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Energy-adjusted Dietary Inflammatory Index (E-DII), constructed based on 26 or 27 nutrients, was analyzed using continuous or categorical methods. Logistic regression and restricted cubic spline analyses examined the association between E-DII and abdominal pain.

Results

In UK Biobank, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.12 (95% CI 1.02–1.24; P = .022), 1.05 (95% CI 1.00–1.09; P = .030), 1.26 (95% CI 1.17–1.36; P < .001), and 1.10 (95% CI 1.00–1.20; P = .044) for chronic abdominal pain, abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, respectively. In NHANES, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.46 (95% CI 1.20–1.77;P < .001), 1.75 (95% CI 1.20–2.60; P = .005), 1.45 (95% CI 1.14–1.87; P = .003), and 1.18 (95% CI 0.82–1.72; P = .380) for abdominal pain in the past year, upper left abdominal pain, upper middle abdominal pain, and upper right abdominal pain. Additionally, there was a nonlinear correlation between E-DII score and DHQ-3Q (P nonlinear <.001).

Conclusion

Following a pro-inflammatory diet is linked to a higher likelihood of experiencing abdominal pain, as well as increased severity and frequency of such pain. Therefore, further longitudinal studies are necessary to investigate this relationship.
Persistent microbial communities in hyperarid subsurface habitats of the Atacama Desert: Insights from intracellular DNA analysis
Authors: Horstmann Lucas , Lipus Daniel , Bartholomäus Alexander , Arens Felix , Airo Alessandro , Ganzert Lars , Zamorano Pedro , Schulze-Makuch Dirk , Wagner Dirk
Published: April 2024

Desert environments constitute one of the largest and yet most fragile ecosystems on Earth. Under the absence of regular precipitation, microorganisms are the main ecological component mediating nutrient fluxes by using soil components, like minerals and salts, and atmospheric gases as a source for energy and water. While most of the previous studies on microbial ecology of desert environments have focused on surface environments, little is known about microbial life in deeper sediment layers. Our study is extending the limited knowledge about microbial communities within the deeper subsurface of the hyperarid core of the Atacama Desert. By employing intracellular DNA extraction and subsequent 16S rRNA sequencing of samples collected from a soil pit in the Yungay region of the Atacama Desert, we unveiled a potentially viable microbial subsurface community residing at depths down to 4.20 m. In the upper 80 cm of the playa sediments, microbial communities were dominated by Firmicutes taxa showing a depth-related decrease in biomass correlating with increasing amounts of soluble salts. High salt concentrations are possibly causing microbial colonization to cease in the lower part of the playa sediments between 80 and 200 cm depth. In the underlying alluvial fan deposits, microbial communities reemerge, possibly due to gypsum providing an alternative water source. The discovery of this deeper subsurface community is reshaping our understanding of desert soils, emphasizing the need to consider subsurface environments in future explorations of arid ecosystems.
Causal association of genetically determined caffeine intake from tea or coffee with bone health: a two-sample Mendelian randomization study
Authors: Li Gloria Hoi-Yee , Tang Ching-Man , Wu Suet-Man , Cheung Ching-Lung
Published: April 2024

Background

Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata.

Methods

Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent.

Results

In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006–0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654–0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093–0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45–60 years, but we lacked evidence of association in other strata.

Conclusions

Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk.
republic: A variability-preserving systematic-correction algorithm for PLATO’s multi-camera light curves
Authors: Barragán Oscar , Aigrain Suzanne , McCormac James
Published: April 2024

Space-based photometry missions produce exquisite light curves that contain a wealth of stellar variability on a wide range of time-scales. Light curves also typically contain significant instrumental systematics – spurious, non-astrophysical trends that are common, in varying degrees, to many light curves. Empirical systematics-correction approaches using the information in the light curves themselves have been very successful, but tend to suppress astrophysical signals, particularly on longer time-scales. Unlike its predecessors, the PLAnetary Transits and Oscillations of stars (PLATO) mission will use multiple cameras to monitor the same stars. We present republic, a novel systematics-correction algorithm which exploits this multi-camera configuration to correct systematics that differ between cameras, while preserving the component of each star’s signal that is common to all cameras, regardless of time-scale. Through simulations with astrophysical signals (star spots and planetary transits), Kepler-like errors, and white noise, we demonstrate republic’s ability to preserve long-term astrophysical signals usually lost in standard correction techniques. We also explore republic’s performance with different number of cameras and systematic properties. We conclude that republic should be considered a potential complement to existing strategies for systematic correction in multi-camera surveys, with its utility contingent upon further validation and adaptation to the specific characteristics of the PLATO mission data.
Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques
Authors: Held Julia , Schwabl Christoph , Haschka David , Maier Sarah , Feuchtner Gudrun , Widmann Gerlig , Duftner Christina , Weiss Günter , Klauser Andrea
Published: April 2024

Objective

To determine the association of cardiovascular atherosclerotic plaque monosodium urate deposits with the occurrence of major cardiovascular events in gout and hyperuricemia patients.

Methods

This retrospective cohort study included patients with clinically suspicion of gout, who performed a dual energy computed tomography of the affected limb and thorax between 1 June 2012 and 5 December 2019. Clinical and laboratory parameters were retrieved from patients’ charts. Established cardiovascular risk factors were evaluated. Medical history review identified the presence of major adverse cardiac events with a median follow-up time of 33 months (range 0–108 months) after the performed computed tomography scan.

Results

Full data sets were available for 189 patients: 131 (69.3%) gout patients, 40 (21.2%) hyperuricemia patients and 18 (9.5%) controls. Patients with cardiovascular monosodium urate deposits (n = 85/189, 45%) revealed increased serum acute phase reactants, uric acid levels and calcium scores in computed tomography compared with patients without cardiovascular monosodium urate deposits. Major adverse cardiac events were observed in 35 patients (18.5%) with a higher prevalence in those patients revealing cardiovascular monosodium urate deposits (n = 22/85, 25.9%) compared with those without cardiovascular monosodium urate deposits (n = 13/104, 12.5%, OR 2.4, P = 0.018).

Conclusion

This is the first study demonstrating the higher hazard of major adverse cardiac events in patients with dual energy computed tomography-verified cardiovascular monosodium urate deposits. The higher prevalence of cardiac events in patients with cardiovascular monosodium urate deposits may facilitate risk stratification of gout patients, as classical cardiovascular risk scores or laboratory markers fail in their proper identification.
Exploring the impact of polystyrene microplastics on human health: unravelling the health implications of polystyrene microplastics (PS-MPs): a comprehensive study on cytotoxicity, reproductive health, human exposure, and exposure assessment
Authors: Dilip Bhandare Saurabh
Published: April 2024

This investigation explores the various impacts that polystyrene microplastics (PS-MPs) have on human health. As most of the plastic materials affect human health when they release leachable toxic substances that affect human health, this causes a negative effect that determines poor health conditions and leads to health hazards associated with plastic toxins routed in the human body, such as: Polychlorinated Biphenyls, Polybrominated Biphenyls etc. The study includes micro-plastic exposure assessment on testicular structure analysis, and cytotoxicity evaluations of different human cell types. The findings clarified the possible dangers of PS-MPs exposure from food, medications, and common products, emphasising the necessity of standard specimen handling procedures for precise biomonitoring.
Examining the Association between Immunosuppressants and Wound Healing: A Narrative Review
Authors: Appoo Aria , Christensen Brandon L. , Somayaji Ranjani
Published: April 2024

Objective

To review how different classes of immunosuppressants affect wound healing.

Data Sources

A literature search was conducted in PubMed, Google Scholar, and the University of Calgary Health Sciences Library.

Study Selection

The researchers initially screened article titles using key words such as “immunosuppressive medication,” “wound healing,” and “immunosuppression.” Articles in which the title and/or abstract contained these key words, that addressed wound healing related to immunosuppressant medications, and were published after 2000 were included in the review. When human data were not available for an immunosuppressant (class), animal studies were included.

Data Extraction

The 61 included articles underwent full text review and summarization.

Data Synthesis

All included studies were summarized descriptively including immunosuppressive mechanism of action, study participants or subjects, and evidence of effects on wound healing.

Conclusions

Corticosteroids and mechanistic target of rapamycin inhibitors most consistently demonstrate detrimental effects on wound healing. For other classes of immunosuppressants, evidence is limited with varying effects on wound healing described. Larger, high-quality studies are required to better understand the effects of immunosuppressants, including those with new mechanisms of action, to identify those with the most impact on wound healing.
The Effect of Stoma Site Marking on Stomal Complications: A Long-term Retrospective Study
Authors: Guler Sevil , Eyuboglu Gulcan , Baykara Zehra Gocmen , Hin Aysel Oren , Akdemir Hülya , Akar Emine , Leventoglu Sezai , Yuksel Osman
Published: April 2024

OBJECTIVE

To identify the effect of stoma site marking on stoma-related complications.

METHODS

The study sample included 639 individuals with stomas who were followed up in a stomatherapy unit in Turkey between January 1, 2017, and June 20, 2021. Researchers collected patient data from nursing records. Data were evaluated using number, percentage, χ
2, and logistic regression tests.

RESULTS

Of the individuals with stomas, 60.6% (n = 387) were men, and 72.6% (n = 464) had a cancer diagnosis. Their mean age was 60.16 (SD, 14.81) years. The stoma site was marked preoperatively in of 67.1% of patients (n = 429), and 17.1% (n = 109) developed stoma-related complications. The complication rate was higher in individuals with unmarked stoma sites (25.7%; P = .000), emergency surgeries (25.0%; P = .006), colostomies (23.9%; P = .042), and permanent stomas (28.3%; P = .002). The three most common complications were peristomal skin problems (56.9%), mucocutaneous separation (13.8%), and edema (9.2%).

CONCLUSIONS

The incidence of stoma-related complications in the postoperative period was higher in individuals with unmarked stoma sites. The authors recommend that stoma and wound care nurses mark the stoma site in individuals for whom stoma creation is planned.
Multicenter, Prospective, Observational Trial of Nonoperative Versus Operative Treatment for High-Energy Midshaft Clavicle Fractures
Authors: Jeray Kyle J. , Broderick J. Scott , Mullis Brian H. , Everhart Joshua , Tanner Stephanie L. , Snider Becky G. ,   On behalf of Southeastern Fracture Consortium
Published: April 2024

OBJECTIVES:

Evaluate if nonoperative or operative treatment of displaced clavicle fractures delivers reduced rates of nonunion and improved DASH scores

METHODS:

Design: Multicenter, prospective, observational

Setting:

Seven Level 1 Trauma Centers in the United States

Patient Selection Criteria:

Adults with closed, displaced (100% displacement/shortened >1.5cm) midshaft clavicle fractures (OTA 15.2) treated nonoperatively, with plates and screw fixation, or with intramedullary fixation from 2003-2018.

Outcome Measures and Comparisons:

DASH scores (2 weeks, 6 weeks, 3, 6, 12, and 24 months), reoperation, and nonunion were compared between the nonoperative, plate fixation, and intramedullary fixation groups.

RESULTS:

412 patients were enrolled, with 203 undergoing plate fixation, 26 receiving intramedullary fixation, and 183 treated nonoperatively. The average age of the nonoperative group was 40.1 (range 18-79) years versus 35.8 (range 18-74) in the plate group and 39.3 (range 19-56) in the intramedullary fixation group (p=0.06). 140 (76.5%) patients in the nonoperative group were male compared to 154 (75.9%) in the plate group and 18 (69.2%) in the intramedullary fixation group (p=0.69). All groups showed similar DASH scores at 2 weeks, 12 and 24 months (p>0.05). Plate fixation demonstrated better DASH scores (median=20.8) than nonoperative (median=28.3) at 6 weeks (p=0.04). Intramedullary fixation had poorer DASH scores at 6 weeks, 3 and 6 months than plate fixation and worse DASH scores than nonoperative at 6 months (p<0.05). The nonunion rate for nonoperative treatment (14.6%) was significantly higher than the plate group (0%) (p<0.001).

CONCLUSION:

Operative treatment of displaced clavicle fractures provided lower rates of nonunion than nonoperative treatment. Except at 6 weeks, no difference was observed in DASH scores between plate fixation and nonoperative treatment. Intramedullary fixation resulted in worse DASH scores than plate fixation at 6 weeks, 3 and 6 months, and worse DASH scores than nonoperative at 6 months. Implant removal was the leading reason for reoperation in the plate and intramedullary fixation groups, while surgery for nonunion was the primary reason for surgery in the nonoperative group.

LEVEL OF EVIDENCE:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Characteristics and Outcomes of Occult Infections in Presumed Aseptic Nonunions: A Retrospective Cohort Study
Authors: Wagner Robert Kaspar , Emmelot Mees P. , van Trikt Clinton , Visser Caroline E. , Peters Edgar J.G. , Janssen Stein J. , Kloen Peter
Published: April 2024

OBJECTIVES:

To determine (1) the rate of positive cultures in presumed aseptic nonunions, (2) the rate and microbial spectrum of positive cultures that represented occult infection, and (3) rates of nonunion healing.

METHODS:

Design:

Retrospective cohort study.

Setting:

Tertiary referral center.

Patients Selection Criteria:

Adult patients with a presumed aseptic nonunion treated with single-stage revision between 2002 and 2022.

Outcome Measures and Comparisons:

The rate of positive cultures compared for 2 protocols: old: 1–2 samples cultured 7 days versus new: 5 samples cultured 14 days. The rate of positive cultures meeting occult infection criteria with the new protocol (≥2 samples with phenotypically indistinguishable microorganisms, or ≥1 sample with a high virulent microorganism). Nonunion healing rates between protocols and between groups based on culture results with the new protocol.

RESULTS:

One hundred seventy-nine patients were included. The rate of positive cultures was 14% (n = 15/105) with the old protocol and 51% (n = 38/74) with the new protocol (P < 0.001). With the new protocol, the rate of positive cultures meeting occult infection criteria was 19% (n = 14/74), and coagulase-negative staphylococci (48%) and Cutibacterium acnes (38%) were the most common microorganisms. Nonunion healing rates after the primary revision did not differ between protocols (old: 82% vs. new: 86%, P = 0.41) and groups based on culture result (sterile: 86% vs. occultly infected: 93%, P = 0.66). The final overall nonunion healing rate was 97%.

CONCLUSIONS:

Occult infections were identified in 1 in 5 presumed aseptic nonunions using a standardized protocol with 5 intraoperative samples cultured 14 days and were predominantly caused by slow growing, gram-positive microorganisms. The local spectrum and antimicrobial sensitivity of occult infections should be considered when developing empiric antimicrobial protocols. Patients with presumed aseptic nonunions can expect high healing rates, regardless of the culture result.

LEVEL OF EVIDENCE:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
JFH1-based Core-NS2 genotype variants of HCV with genetic stability in vivo and in vitro: Important tools in the evaluation of virus neutralization
Authors: Collignon Laura , Holmbeck Kenn , Just Ashley , Verhoye Lieven , Velázquez-Moctezuma Rodrigo , Fahnøe Ulrik , Carlsen Thomas H. R. , Law Mansun , Prentoe Jannick , Scheel Troels K. H. , Gottwein Judith M. , Meuleman Philip , Bukh Jens
Published: April 2024

Background and Aims:

HCV infection continues to be a major global health burden despite effective antiviral treatments. The urgent need for a protective vaccine is hindered by the scarcity of suitable HCV-permissive animal models tractable in vaccination and challenge studies. Currently, only antibody neutralization studies in infectious cell culture systems or studies of protection by passive immunization of human liver chimeric mice offer the possibility to evaluate the effect of vaccine-induced antibodies. However, differences between culture-permissive and in vivo–permissive viruses make it a challenge to compare analyses between platforms. To address this problem, we aimed at developing genotype-specific virus variants with genetic stability both in vitro and in vivo.

Approach and Results:

We demonstrated infection of human liver chimeric mice with cell culture–adapted HCV JFH1-based Core-NS2 recombinants of genotype 1–6, with a panel of 10 virus strains used extensively in neutralization and receptor studies. Clonal re-engineering of mouse-selected mutations resulted in virus variants with robust replication both in Huh7.5 cells and human liver chimeric mice, with genetic stability. Furthermore, we showed that, overall, these virus variants have similar in vitro neutralization profiles as their parent strains and demonstrated their use for in vivo neutralization studies.

Conclusions:

These mouse-selected HCV recombinants enable the triage of new vaccine-relevant antibodies in vitro and further allow characterization of protection from infection in vivo using identical viruses in human liver chimeric mice. As such, these viruses will serve as important resources in testing novel antibodies and can thus guide strategies to develop an efficient protective vaccine against HCV infection.
Prevalence and Predictors of Follow-up Endoscopic Biopsy in Patients With Celiac Disease in the United States
Authors: Venkat Manu V. , Chen Ling , Wright Jason D. , Lebwohl Benjamin
Published: April 2024

Objective:

To characterize the frequency and predictors of follow-up endoscopic biopsy in patients with celiac disease.

Background:

The utility of routine follow-up biopsy in patients after a diagnosis of celiac disease is uncertain, especially in patients whose symptoms resolve on the gluten-free diet.

Patients and Methods:

Using the Merative MarketScan U.S. commercial insurance and Medicare databases, we identified 30,737 patients with biopsy-diagnosed celiac disease. We followed them until they had a second duodenal biopsy (our primary outcome) or insurance coverage ended.

Results:

Among the patients with celiac disease we identified, 5976 (19.4%) underwent a follow-up biopsy. The median time between initial and follow-up biopsies was 16.8 months. Compared with younger patients, those aged 20 years or older had an increased likelihood of undergoing a follow-up biopsy (cumulative incidence rate at 5 y for patients age ≥20 y was 36.0%, 95% CI: 35.0%-37.1% vs 21.9%, 95% CI: 20.5%-23.4% in patients age ≤19 y). Follow-up biopsies occurred less frequently in more recent calendar years. Follow-up biopsy was more common among patients with an Elixhauser Comorbidity Index of 1 (hazard ratio: 1.09; 95% CI: 1.01-1.17) or ≥2 (hazard ratio: 1.28; 95% CI: 1.20-1.37) compared with patients with an index of zero. Among patients who had a follow-up biopsy, 57% had a celiac disease-related symptom recorded in the 30 days before the procedure.

Conclusions:

Follow-up duodenal biopsy is performed in a substantial minority of U.S. patients with celiac disease. Adult age and increased comorbidity burden were associated with a greater likelihood of follow-up biopsy. Just under half of follow-up biopsies are performed for routine surveillance, in the absence of persistent symptoms.
Nomogram predicting survival in patients with lymph node-negative hepatocellular carcinoma based on the SEER database and external validation
Authors: Li Ziqiang , Hong Qingyong , Li Kun
Published: April 2024

Background

The relationship between lymph node (LN) status and survival outcome in hepatocellular carcinoma (HCC) is a highly controversial topic. The aim of this study was to investigate the prognostic factors in patients without LN metastasis (LNM) and to construct a nomogram to predict cancer-specific survival (CSS) in this group of patients.

Methods

We screened 6840 eligible HCC patients in the Surveillance, Epidemiology and End Results（SEER）database between 2010 and 2019 and randomized them into a training cohort and an internal validation cohort, and recruited 160 patients from Zhongnan Hospital of Wuhan University as an external validation cohort. Independent prognostic factors obtained from univariate and multivariate analysis were used to construct a nomogram prediction model. The concordance index (C-index), area under curve (AUC), calibration plots and decision curve analysis (DCA) were used to assess the predictive power and clinical application of the model.

Results

Univariate and multivariate analysis revealed age, gender, bone metastasis, lung metastasis, AFP, T stage, surgery and chemotherapy as independent prognostic factors. The C-index of the constructed nomogram for the training cohort, internal validation cohort and external validation cohort are 0.746, 0.740, and 0.777, respectively. In the training cohort, the AUC at 1-, 3-, and 5-year were 0.81, 0.800, and 0.800, respectively. Calibration curves showed great agreement between the actual observations and predictions for the three cohorts. The DCA results suggest that the nomogram model has more clinical application potential.

Conclusion

We constructed a nomogram to predict CSS in HCC patients without LNM. The model has been internally and externally validated to have excellent predictive performance and can help clinicians determine prognosis and make treatment decisions.
Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease
Authors: Evenepoel Pieter , Jørgensen Hanne Skou
Published: April 2024

Purpose of review

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD.

Recent findings

Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness.

In summary

Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.
Characterizing autoimmune uveitis to systemic diseases: a retrospective study from a Syrian tertiary reference center
Authors: Kudsi Maysoun , Al-Darwish Lama , Khalayli Naram , Abouharb Dani , Abouharb Lana , Almajzoub Rahaf , Deeb Haya
Published: April 2024

Background:

Uveitis, a notable cause of severe visual impairment, is frequently characterized as infectious or noninfectious autoimmune uveitis (AU), the latter of which is commonly associated with younger individuals and systemic diseases. Despite the condition’s widespread impact, there are substantial gaps in the comprehension of its pathogenesis, clinical presentation, and therapeutic response, particularly concerning systemic disease-associated uveitis.

Aim of the study:

The current study aims to bridge these gaps through an extensive examination of demographic and clinical features in AU patients, thereby informing future research, and therapeutic strategies, and improving patient outcomes.

Methods:

This retrospective observational study analyzed 261 patients with systemic disease-associated uveitis from January 2018 to December 2022 in Damascus, Syria. With diagnoses made using the Standardization of Uveitis Nomenclature Working Group Criteria, the study evaluated tailored treatment efficacy at the 24-month post-treatment mark, alongside comprehensive ophthalmic examinations, laboratory evaluations, and radiographic assessments.

Results:

In our study, included 87 patients with Systemic Disease-Associated Autoimmune Uveitis (SDA-AU). Women represented 64.36% of this group, and the mean age at diagnosis was 39.8±17.9 years (range 7–71) for men and 43.8±15.4 years (range 11–69). The most reported symptom was a painful red eye (52.87%). The onset of symptoms was sudden for 32.18% of patients, while 67.81% reported gradual development. Complications occurred in 33.33% of patients, including cataracts (41.37% of those with complications) and glaucoma (17.24%). Laboratory evaluations showed elevated inflammation markers in 66.66% of patients. Upon the 24-month assessment, 48.27% of patients achieved complete remission, 37.93% showed significant improvement, while disease worsened in 13.79% of cases.

Conclusion:

Our findings demonstrated that the presentation of AU in this cohort frequently precedes the diagnosis of systemic diseases, affirming the vital role of an early and accurate diagnosis of uveitis for the detection of underlying systemic conditions. In conclusion, our study underlines the significance of a comprehensive and multidisciplinary approach in the management of SD-AU, leading to improved prognosis and quality of life for patients.
Identification of important symptoms and diagnostic hypothyroidism patients using machine learning algorithms
Authors: Rakhshani Rad Salahuddin , Mohammadi Zahra H. , Zadeh Mahdieh J. , Mosleh-Shirazi Mohammad A. , Dehesh Tania
Published: April 2024

Background:

Hypothyroidism is one of the most common endocrine diseases. It is, however, usually challenging for physicians to diagnose due to nonspecific symptoms. The usual procedure for diagnosis of Hypothyroidism is a blood test. In recent years, machine learning algorithms have proved to be powerful tools in medicine due to their diagnostic accuracy. In this study, the authors aim to predict and identify the most important symptoms of Hypothyroidism using machine learning algorithms.

Method:

In this cross-sectional, single-center study, 1296 individuals who visited an endocrinologist for the first time with symptoms of Hypothyroidism were studied, 676 of whom were identified as patients through thyroid-stimulating hormone testing. The outcome was binary (with Hypothyroidism /without Hypothyroidism). In a comparative analysis, random forest, decision tree, and logistic regression methods were used to diagnose primary Hypothyroidism.

Results:

Symptoms such as tiredness, unusual cold feeling, yellow skin (jaundice), cold hands and feet, numbness of hands, loss of appetite, and weight Hypothyroidism gain were recognized as the most important symptoms in identifying Hypothyroidism. Among the studied algorithms, random forest had the best performance in identifying these symptoms (accuracy=0.83, kappa=0.46, sensitivity=0.88, specificity=0.88).

Conclusions:

The findings suggest that machine learning methods can identify Hypothyroidism patients who show relatively simple symptoms with acceptable accuracy without the need for a blood test. Greater familiarity and utilization of such methods by physicians may, therefore, reduce the expense and stress burden of clinical testing.
Effects on ondansetron of postdural puncture headache after cesarean section under spinal anesthesia
Authors: Baharvand Forough , Vahabi Sepideh , Beiranvand Siavash
Published: April 2024

Background:

Spinal anesthesia is commonly performed for cesarean section, however, postdural puncture headache (PDPH) is one of its most common adverse effects. Ondansetron is an antiemetic for cancer treatment and analgesia-induced nausea and vomiting. In this study, the authors aim to evaluate the effect of postoperative ondansetron on PDPH.

Methods:

In this randomized controlled clinical trial study, 120 pregnant patients are ASA ll, undergoing elective cesarean section, were randomized into two groups (placebo or study). The patients in the study group, immediately after the birth of a baby and 24 h after the operation, received ondansetron 4 mg IV while the placebo group received a placebo. The severity and incidence of headache, postoperative nausea and vomiting, dizziness, neck and lower back pain, and the use of analgesia was assessed in the two groups.

Results:

The significant meaning of the time effect (P<0.001) indicated that regardless of the group, for each unit increase in time, the chance of developing a headache increased by 23%, which was statistically significant. Also, the significant meaning of the group effect indicated that regardless of time, patients who did not take indomethacin had ~4.11 times higher chances of developing a headache compared to those who received the medication, which was statistically significant (P=0.004).

Conclusion:

The administration of ondansetron significantly reduces the occurrence of postspinal anesthesia headaches and neck pain. There was no significant difference in headache severity between the two study groups.
What is the materno-fetal prognosis of adrenal insufficiency and pregnancy in low-resource setting? a case report
Authors: Soumana Diaouga Hamidou , Ziberou Assadick Oumar , Chaibou Yacouba Maimouna , Oumara Maina , Guédé Salamatou , Adamou Abdoulkader , Adehossi Eric O. , Mahamane Sani Mahamane A. , Nayama Madi
Published: April 2024

Introduction and importance:

Adrenal insufficiency is a rare chronic disease with a prevalence of 39 to 60 cases per million peoples in Europe. However, the prevalence is higher in sub-saharian Africa. The occurrence of pregnancy in adrenal insufficiency is rare but associated with high maternal and perinatal morbidity and mortality. For this reason, the management of pregnancy in adrenal insufficiency patient must be provided by a multidisciplinary team.

Case presentation:

The authors report the case of a 34-year-old pregnant woman followed for adrenal insufficiency secondary to prolonged corticosteroid therapy. Treatment consisted to an obstetrical and endocrinological follow-up and corticosteroid replacement therapy with hydrocortisone. A prophylactic cesarean section at 38 weeks resulted in the birth of a newborn male weighing 3395 g. Maternal and perinatal prognosis was good.

Clinical discussion:

Pregnancy in adrenal insufficiency is a therepeutic challenge in developing countries. Through this case, the authors discuss the therapeutic and prognostic aspects of adrenal insufficiency in our setting.

Conclusion:

With the introduction of gluco-corticosteroid replacement therapy, pregnancy in adrenal insufficiency can progress normally.
Malignancy and “Violated Neck” Rates in Consecutive Cohort of 79 Adult Patients With Solitary Cystic Neck Mass—Lessons Learned and Recommendations for Clinical Practice Guidelines
Authors: Pupić-Bakrač Jure , Jayasekara Sandeep , Peiris Prasangi M. , Jayasinghe Liyanaarachchige A.H. , Kapugama Kanchana , Jayasuriya Nadeena S.S. , Wijekoon Parakrama , Attygalla Manjula
Published: April 2024

Objective:

The neck region is a common site for solitary cystic neck mass (SCNM) of various etiologies, including congenital, inflammatory, and neoplastic. In adults, the primary focus is excluding malignancy. The objective of this study was to retrospectively analyze the accuracy of available diagnostic technologies for the differentiation of benign and malignant SCNM in adult patients. The study aimed to develop new clinical practice guidelines for evaluating and managing SCNM.

Methods:

The primary predictive variables were the diagnostic utilities of fine-needle aspiration cytology (FNAC), ultrasound (U/S), multislice computed tomography, and magnetic resonance imaging. The study’s endpoint was the overall diagnostic accuracy in differentiating between benign and malignant SCNM. The final diagnosis was based on histopathology.

Results:

The study included 79 adult patients: 55 (69.62%) male and 24 (30.38%) female (P<0.05). The mean age at presentation was 42.1 years (range: 18–84 years). Solitary cystic neck mass was distributed in the anterior neck region in 30 (37.97%) patients and the posterolateral neck regions in 49 (62.03%) patients (P<0.05). The posterolateral neck regions had a significantly higher rate of malignant SCNM than the anterior neck region [19/49 (38.78%) versus 1/30 (3.33%)] (P<0.05). There was no statistically significant difference between the U/S+FNAC and U/S+FNAC+multislice computed tomography and/or magnetic resonance imaging groups in differentiating benign and malignant SCNM (40/42 versus 36/37, P>0.05). “Violated neck” was recorded in 2 cases.

Conclusion:

A systematic investigation protocol should be applied to evaluate adult patients with SCNM.
Bisphenol A and its Analogues Alter Appetite Control in Zebrafish
Authors: Karim Silvia , Bondesson Maria
Published: April 2024

The regulation of appetite is of growing interest due to the significant rise in global obesity rates. Hunger and satiety are controlled by two hormones with functional activity in the brain; leptin, which is produced in adipocytes and suppresses food intake, and ghrelin, which is produced and released mainly by the stomach and functions as an appetite-stimulatory signal. In this study, zebrafish-basedin vivoassays were used to examine whether BPA and five of its analogues, BPAF, BPE, BPC, BPC-CL, and BPS affect appetite regulation. The effect of bisphenol exposure on eating behavior was first examined. Four to six days old zebrafish larvae were exposed to a concentration range of the bisphenols and 17β-estradiol, followed by being fed a stained egg yolk powder at day six. After an hour of feeding, the feed in the gut was imaged by microscopy. Quantitative PCR was used to analyze the gene expression ofleptinandghrelin, as well as eleven other genes involved in appetite control. Exposures to BPA, BPAF, BPE, BPC, BPC-Cl and BPS, resulted in increased amounts of feed in the gut of the larvae in a concentration dependent manner. The qPCR results suggested thatleptinmRNA expression was downregulated with the increasing concentrations of BPA, BPAF and BPC-Cl, whereasghrelinmRNA expression was upregulated. The expression of several additional anorexigenic genes were downregulated by BPAF and BPC-Cl exposure, whereas orexigenic genes were upregulated. In conclusion, bisphenol exposures resulted in an increased eating behavior in zebrafish larvae, which correlated to increased mRNA expression of appetite-stimulatory genes and decreased expression of satiety-inducing genes. In addition, the results suggest that zebrafish larvae can be used to efficiently assess obesogenic capacity of environmental pollutants.