bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microbiome-restorative potential of ibezapolstat for the treatment of
Clostridioides difficile
infection is predicted through variant PolC-type DNA polymerase III in Lachnospiraceae and Oscillospiraceae
Authors: McPherson Jacob K. , Hurdle Julian G. , Baker Matthew L. , Hussain Tahir , Kumar Ashok , Garey Kevin W. 
Published: February 2025

ABSTRACT

Ibezapolstat (IBZ), a first-in-class antibiotic targeting the PolC-type DNA polymerase III alpha-subunit (PolC) in low G + C bacteria, is in clinical development for the treatment of
Clostridioides difficile
infection (CDI). In the phase 2 trials, IBZ had potent activity against
C. difficile
while sparing or causing regrowth of Lachnospiraceae, Oscillospiraceae, and Erysipelotrichales, common commensal low G + C bacteria. The purpose of this study was to utilize
in silico
approaches to better interpret the narrower than expected IBZ spectrum of activity. IBZ susceptibility to human commensal microbiota was predicted using genomic analysis and PolC phylogenetic tree construction in relation to
C. difficile
and commensal low G + C bacteria. Protein structure prediction was performed using AlphaFold2 and binding pocket homology modeling was performed using Schrodinger Maestro and UCSF ChimeraX. An amino acid phylogenetic tree identified certain residues that were phylogenetically variant in Lachnospiraceae, Oscillospiraceae, and Erysipelotrichales and conserved in
C. difficile
. Chemical modeling showed that these residues ablated key PolC•IBZ predicted interactions including two lysine “
gates
” (
CdiPolC
Lys1148 and
CdiPolC
Lys1327) that “
latch
” onto the compound; an “
anchoring
” interaction (
CdiPolC
Thr1331) to the central moiety; and a stabilized set of
C. difficile
sensitizer residues (
CdiPolC
Thr1291 and
CdiPolC
Lys1292) that resulted in the prolonged inhibition of a catalytic residue (
CdiPolC
Asp1090). The observed IBZ sparing of Lachnospiraceae, Oscillospiraceae, and Erysipelotrichaceae/Coprobacillaceae was predicted using
in silico
techniques. Further studies that confirm a PolC structural basis for the IBZ narrower than expected activity are needed to confirm these
in silico
phylogenetic and chemical modeling data.
Record High Critical Temperature Among Bismuthides of the 122 Family: BaAg1.8Bi2 with a Monoclinically Distorted CaBe2Ge2 Structure
Authors: Sadakov A. V. , Usoltsev A. S. , Vlasenko V. A. , Gavrilkin S. Yu. , Shilov A. I. , Pervakov K. S. , Rakhmanov E. O. , Morozov I. V. 
Published: February 2025

A new superconductor BaAg1.8Bi2 with a previously unknown variant of the monoclinically distorted CaBe2Ge2 structure (space group C2/m) has been crystallized in the form of single crystals from a bismuth flux. The temperature and magnetic field dependences of the magnetic susceptibility and resistance have shown that this compound transits to a superconducting state at the temperature T
c = 5.4 K. According to the found Ginzburg–Landau parameter κ = 27, this compound is a type-II superconductor with the first and second critical fields H
c1(0) = 53 Oe and H
c2(0) = 2.1 × 104 Oe and the critical current density reaching 4.4 kA/cm2 at 2.5 K. It can be assumed that, similar to some superconducting 112 type bismuthides, superconductivity in this compound is due to the planar square bismuth sublattice contained in the fluorite-like [BiAg0.8] layer rather than to the [AgBi] layers where Ag atoms are locally disordered. This could explain the unusually high T
c value for bismuthides belonging to the CaBe2Ge2 structural type and its derivatives.
Association of genetic liability to allergic diseases with overall and early-onset colorectal cancer risk: a Mendelian randomization study
Authors: Alduhayh Saleh , Laskar Ruhina Shirin , Jiang Xia , Zhu Zhaozhong , Vincent Emma E. , Constantinescu Andrei-Emil , Buchanan Daniel D. , Grant Robert C. , Phipps Amanda I. , Brenner Hermann , Huang Wen-Yi , Kweon Sun-Seog , Li Li , Pearlman Rachel , Castellví-Bel Sergi , Gruber Stephen B. , Li Christopher I. , Pellatt Andrew , Platz Elizabeth A. , Van Guelpen Bethany , Zheng Wei , Chan Andrew T. , Figueiredo Jane C. , Ogino Shuji , Ulrich Cornelia M. , Gunter Marc J. , Haycock Philip , Severi Gianluca , Murphy Neil , Dimou Niki 
Published: February 2025

Abstract
Background: Tumor immunosurveillance theory supports that allergic conditions could decrease cancer risk. However, observational evidence yielded inconsistent results for the association between allergic diseases and colorectal cancer risk. We used Mendelian randomization (MR) to examine potential causal associations of allergies with risk of overall and early-onset colorectal cancer. Methods: Genome-wide association study summary statistic data were used to identify genetic variants associated with allergic diseases (Nvariants=65) and individual allergic conditions (asthma, hay fever/allergic rhinitis, eczema). Using two-sample MR, we examined these variants in relation to incident overall (Ncases=52,775 cases) and early-onset colorectal cancer (Ncases=6,176). The mediating role of white blood cells was examined using multivariable MR. Results: In inverse-variance weighted models, genetic liability to allergic diseases was inversely associated with overall (ORper log(odds)= 0.90 [95% CI= 0.85-0.96]; P&lt; 0.01) and early-onset colorectal cancer (OR= 0.83 [95% CI= 0.73-0.95]; P= 0.01). Similar inverse associations were found for hay fever/allergic rhinitis or eczema, while no evidence of association was found between liability to asthma-related phenotypes and colorectal cancer risk. Multivariable MR adjustment for eosinophils weakened the inverse associations for liability to allergic diseases for overall (OR= 0.96 [95% CI= 0.89-1.03]; P= 0.26) and early-onset colorectal cancer (OR= 0.86 [95% CI= 0.73-1.01]; P= 0.06). Conclusions: Our study supports a potential causal association between liability to allergic diseases, specifically hay fever/allergic rhinitis or eczema, and colorectal cancer, possibly at least in part mediated via eosinophil counts. Impact: Our results provide evidence that allergic responses may also have a role in immunosurveillance against colorectal cancer.
Landfall-induced changes in Tropical Cyclone Veronica’s surface winds
Authors: Kepert Jeffrey D. 
Published: February 2025

Abstract
Severe Tropical CycloneVeronica impacted theAustralian northwest coast in March 2019. Synthetic-aperture radar observations showed that the eyewall wind maximum shifted from the left forward quadrant, characteristic of the motion-induced asymmetry for Southern Hemisphere storms, to the right forward quadrant as Veronica approached land. Analysis of a large body of similar observations showed that the majority of cyclones within 200 km of land have an eyewall surface wind asymmetry with the strongest winds in the offshore-flow semicircle, similar to that in Veronica, rather than an asymmetry consistent with motion. In contrast, cyclones further from land mostly have the expected motion-induced asymmetry. Simulations with a dynamical tropical cyclone boundary layer demonstrate that the rightwards shift of the wind maximum in Veronica was consistent with asymmetric surface friction due to the proximity to land. Analysis of the simulated vertical structure revealed that the asymmetry comprised two counter-rotating spirals, similar to those described in a companion paper. The effect of this change in surface wind asymmetry on storm impact is argued to be likely modest, because it occurs largely in the offshore flow, usually away from people and infrastructure.
An easier way to die?—A qualitative interview study on specialist palliative care team members’ views on dying under sedation
Authors: Bazata Jeremias , Meesters Sophie , Bozzaro Claudia , Handtke Violet , Schildmann Jan , Heckel Maria , Ostgathe Christoph , Bausewein Claudia , Schildmann Eva ,   For the SedPall Study Group
Published: February 2025

Background: Professionals’ personal perceptions of sedated patients in the context of palliative care may influence their opinion on sedation as treatment option. However, little is known of palliative care professionals’ perception of patients dying under sedation. Aim: To explore German specialist palliative care team members’ views on and perception of the dying process under sedation. Design: Qualitative phenomenological study using semi-structured interviews ( n = 59). Interviews took place in-person after recruitment via a contact person and were transcribed verbatim. Framework Analysis was used for analysis. Setting/participants: Physicians, nurses, psychologists, physical therapists, chaplains, and social workers from 10 palliative care units and 7 specialist palliative homecare teams across 12 German cities. Results: Participants’ views on patients dying under sedation can be grouped into: (i) those who perceived an influence of sedation on the dying process with and without positive and/or negative connotations and (ii) those who saw no difference between dying with or without sedation. Positive connotations referred to the perception of sedation providing an easier path. Concerns were mainly related to the deprivation of patients regarding a conscious dying. The metaphorical description of sedation as “sleep” was common among participants. Conclusions: The wide range of perceptions of patients dying under sedation may be rooted in different judgements regarding aspects of a good death. Clarifying ideals of a good death with professionals, patients, and relatives before sedation may support transparent decision-making and help avoid conflicts or moral distress.
Percutaneous cryoablation of renal tumors adjacent to critical structures: impact of adjacent organ type on local tumor control
Authors: Ozawa Mizuki , Sone Miyuki , Sugawara Shunsuke , Itou Chihiro , Kimura Shintaro , Kusumoto Masahiko , Matsui Yoshiyuki 
Published: February 2025

Background Renal cell carcinomas (RCCs) adjacent to critical structures can be safely treated using percutaneous cryoablation with adjunctive techniques. However, there are only a few reports describing the factors affecting local tumor control after percutaneous cryoablation for such RCCs. Purpose To evaluate the factors affecting local tumor control in the percutaneous cryoablation of RCCs adjacent to critical structures. Material and Methods A total of 403 tumors from 328 patients were retrospectively reviewed. Patients with histologically proven RCCs adjacent to critical structures with at least 1 year of follow-up after treatment were included. Hereditary RCCs were excluded. Of the 403 tumors, 40 met the criteria. Owing to the tumor location, all procedures were performed using adjunctive techniques. Baseline, perioperative, and follow-up data were collected and factors affecting local tumor progression were evaluated. Comparisons between groups with and without local tumor progression were performed using Fisher's exact test or Wilcoxon's rank sum test. Results The median follow-up was 1289.5 days. Local tumor progression was observed in 7/40 (17.5%) patients. Univariate analysis revealed that significant factors affecting local tumor progression were situated adjacent to the ureter ( P = 0.005), requiring adjunctive techniques other than hydro- and/or pneumo-dissection ( P = 0.005), as well as the distance between tumors and critical structures ( P = 0.04). The ice-ball margin tended to be smaller in the group with local tumor progression but this was not significant ( P = 0.07). Conclusion Renal tumors adjacent to the ureter may result in local tumor progression after cryoablation compared with tumors adjacent to other organs.
Association of low-grade proteinuria with changes of lupus nephritis in kidney biopsy in SLE patients
Authors: Timlin Homa , Koirala Abbal , Gross Matthew , Geetha Duvuru , Kamel Ihab , Atta Mohamed G. 
Published: February 2025

Background A kidney biopsy is essential for definitive histopathological diagnosis in lupus nephritis, informing therapeutic strategies. Current guidelines (ACR and EULAR/ERA-EDTA) do not include a kidney biopsy for patients with isolated proteinuria of less than 500 mg/g. We explored the histopathologic findings in patients with SLE with proteinuria ≤500 mg/g. Methods We conducted a retrospective review of 27 biopsies of lupus patients with proteinuria ≤500 mg/g who underwent a kidney biopsy at Johns Hopkins. Clinical and laboratory data were obtained from a review of the medical records. The study was approved by the Office of Human Subjects Research and Institutional Review Board. Results Most individuals were females (93%) and African American (56%), with a mean age of 42.1 (12.4) years at the time of biopsy. Twelve individuals had no prior history of lupus nephritis. The average creatinine at the biopsy was 1.05 mg/dl, and UPCR was 0.27 grams/gram. Most patients (100%) were on hydroxychloroquine, 41% were on prednisone, and 33% were on mycophenolate mofetil. Kidney biopsies were most commonly performed based on extra-renal disease activity, new-onset or worsening proteinuria (88.9%) and worsening dsdNA levels (55.6%). At the time of biopsy, 55.6% of patients presented with extrarenal lupus, most commonly arthritis or arthralgias and mucosal ulcers. Of the 27 patients, 23 patients had evidence of lupus nephritis (85.1%), including class III (33%), V (30%), III/V (7%), class II (4%) and class I (11%). Nine patients had a UPCR of 200 mg/g or lower. Among these patients, 22% did not show signs of lupus nephritis in the kidney biopsy, 44% had class V LN, and 11% had class I and III LN. Kidney biopsy was well tolerated, with the majority (93%) not developing post-biopsy complications. Conclusions We identified patients with proteinuria ≤500 mg/g who had lupus nephritis, with the majority ranging from Class III to V with only one class II. This study supports that normal or low UPCR <500 mg/g lacks the sensitivity to detect early lupus nephritis. Better biomarkers for the cutoff of biopsy are needed to improve kidney outcomes and trial design.
Improving safety performance through a user-centric knowledge-based system for fall risk assessment
Authors: Chellappa Vigneshkumar , Salve Urmi Ravindra 
Published: February 2025

Background Fall from height (FFH) incidents remain a significant concern in the construction industry worldwide. Experts suggested integrating the knowledge management (KM) concept into safety risk assessment (RA) to improve safety performance. However, a notable gap exists regarding a dedicated KM system for fall RA, particularly for formwork operations. Objective This study aims to develop and evaluate a knowledge-based system that facilitates fall RA for vertical formwork operations in Indian construction projects. Methodology A mixed-method approach was adopted to develop and evaluate the knowledge-based system. First, the Delphi survey was adopted to acquire knowledge from the thirteen experts on causes of falls, individuals at risk, safety risk levels, and preventive measures. Next, the document analysis was conducted to acquire the best safety practices, accident records, research publications, and guidelines/standards for vertical formwork operations. Once the knowledge was captured, a knowledge-based system was designed to store and reuse the acquired knowledge. The proposed system was then evaluated using a survey with the 20 potential end-users based on three criteria: effectiveness, system benefits, and challenges the system addresses. The inter-rater reliability was analyzed using Krippendorff's alpha, a statistical measure assessing consistency among multiple raters. Additionally, the researchers conducted a descriptive statistical analysis of the data. Results The results indicate that the proposed system offers numerous benefits to builders in (1) ensuring that end-users, regardless of their site location, have easy access to vertical formwork safety knowledge; (2) helping users with job site learning of safety RA skills; (3) effectively sharing safety knowledge; (4) facilitating the fall RA process on-the-job for safety heads; (5) helping to improve safety performance; and (6) saving time that is spent on RA. Conclusion The proposed knowledge-based system is anticipated to assist users in making decisions in the construction organizations during vertical formwork activities during fall RA.
Complication Rates and Cost of Endoscopic and Open Surgical Approaches to Management of Craniosynostosis: A Large, National, Inpatient Cohort Evaluation
Authors: Kwon Daniel Y. , Villavisanis Dillan F. , Choe Allison , Seyidova Nargiz , Oleru Olachi , Shamamian Peter , Wang Carol , Sarosi Alex , Taub Peter J. 
Published: February 2025

To compare outcomes, complications, and costs between endoscopic and open surgical approaches in the management of craniosynostosis using a large national database. Retrospective cohort study. National Inpatient Sample database, including inpatient hospital discharge data from 2018 to 2021 across 48 states and Washington, D.C. The present study included 1099 patients admitted with a primary diagnosis of craniosynostosis. Among them, 183 (16.6%) underwent endoscopic surgery and 916 (83.3%) underwent open surgery. Surgical management of craniosynostosis, classified as either an endoscopic or open approach. Length of hospital stay, total procedure costs, and rates of inpatient complications, including surgical and medical complications. Endoscopic surgery was associated with a significantly shorter length of stay (mean 1.6 days vs 3.7 days, P < .001) and lower total costs ($ 66 815.90 vs $ 146 271.21, P < .001) compared to open procedures. It demonstrated lower rates of surgical complications (0.5% vs 7.9%, P < .001) and neurologic complications, primarily dural tears (0.5% vs 7.0%, P < .001). There were no differences in inpatient mortality between groups. Endoscopic approaches to craniosynostosis offer advantages over open techniques, including reduced length of stay, costs, and complications. The present findings support the increasing adoption of endoscopic methods for craniosynostosis management. Future studies should assess the long-term impact on head shape durability and neurodevelopmental outcomes.
Sloughing Esophagitis in the Pediatric Age Group: Clinicopathologic Characteristics of 12 Cases
Authors: Rubrecht Ashlie , Saulino David , Nasri Elham , Esnakula Ashwini K. , Gonzalo David H. , Feely Michael M. , Beasley Genie L , Shenoy Archana 
Published: February 2025

Background: Sloughing esophagitis (esophagitis dissecans superficialis) is a benign, self-limited condition of uncertain etiology. It is most common in adults; pediatric literature is limited. Methods: Ten years of records were queried for esophageal biopsies containing terms “sloughing” and/or “dissecans.” Histologic inclusion criteria were “two-tone” appearance, sloughing/flaking of superficial epithelium, and parakeratosis. Degree of inflammation was documented and medical records were reviewed. Results: Fourteen patients were identified ranging from 1 to 19 years (mean = 14 years) and included 3 males and 11 females. Two patients were excluded due to lack of histologic criteria/unavailability of slides for review. Of the 12 cases evaluated, 6 showed a classic inflammation pattern, 5 had minimal or no inflammation, and 1 displayed severe acute inflammation. Endoscopy did not correlate with histology. Sloughing esophagitis is traditionally associated with Selective serotonin reuptake inhibitors (SSRI) use; though 5/12 patients were taking medication for anxiety or depression, only 3 were taking SSRIs. Five patients had marijuana/cannabinoid exposure. Conclusion: Sloughing esophagitis can present in the pediatric population across a wide age range. Similar to the adult population, etiology may be linked to medications. Additional associations such as marijuana/cannabinoid exposure need further clinical investigation. A subset of patients had a history of or subsequently developed eosinophilic esophagitis.
Evaluation of intraocular pressure and mean ocular perfusion pressure changes following intravitreal anti-VEGF injections
Authors: Colizzi Benedetta , Romano Dario , Lunardon Sofia , Sabbatini Lorenzo , Rossetti Luca Mario 
Published: February 2025

Objective To evaluate changes in intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) following intravitreal anti-VEGF injections (IVI) and to assess influencing factors. Methods In a prospective study, 119 eyes received anti-VEGF IVI, with 60 eyes treated in the supine position and 59 eyes in the seated position. IOP was assessed using an iCare IC200 rebound tonometer before, immediately after, and at 5 and 30 min post-injection. MOPP was calculated at the same time points. Ocular biometric and demographic data were collected to analyze their impact on IOP changes. Results IOP increased from 15.76 ± 4.34 mmHg at baseline to 49.79 ± 15.73 immidiately post-IVI, then decreased to 29.96 ± 10.55 at 5 min and 21.80 ± 7.36 at 30 min. MOPP dropped from 54.02 ± 10.7 mmHg to 35.7 ± 19.7 mmHg immediately post-IVI, recovering to 40.68 ± 15.9 at 5 min and 51.08 ± 12.2 at 30 min. Supine patients exhibited higher IOP, but maintained higher MOPP compared to seated patients. Only 25% of glaucoma patients returned to baseline IOP within 30 min, compared to 48.9% of non-glaucomatous patients (p = 0.02). Phakic patients have greater IOP changes across time, with significant differences at 5 min ( p = 0.03). Conclusion IVI induced IOP increases and MOPP decreases are significant but normalized to baseline +2SD within 30 min in 67.77% and 97.52% of patients. Glaucomatous and phakic patients are at higher risk for prolonged IOP elevation, requiring careful management.
Clinical prediction model for gangrenous appendicitis: A retrospective single-center study
Authors: Suzuki Toshiyuki , Matsumoto Akiyo , Sugiki Daisuke , Akao Takahiko , Matsumoto Hiroshi 
Published: February 2025

Background and aims: Gangrenous appendicitis, a type of complicated appendicitis, is an indication of emergency surgery due to a high risk of perforation. However, it can be challenging to diagnose preoperatively. This study aimed to validate the predictive factors of patients with gangrenous appendicitis and develop a novel scoring model based on objective parameters. Methods: This retrospective single-center study included 171 of 302 consecutive patients undergoing appendectomy between April 2014 and December 2023. Patients with perforation, chronic appendicitis, and appendicitis presenting with an abscess were excluded from the analysis. In other words, the study targeted Grades 1 and 2 on the American Association for the Surgery of Trauma (AAST) severity assessment scale. Computed tomography (CT) scan value was defined as the average value of fluid in the appendix lumen on plain CT scan. Univariate and multivariate analyses were performed to identify the independent objective predictors of gangrenous appendicitis. A new scoring model was developed based on the logistic regression coefficients of the independent predictors. The scores were then classified into three categories, and the probability of gangrenous appendicitis for each category was evaluated. Results: Overall, 46 (27%) and 125 (73%) patients presented with gangrenous appendicitis (=AAST Grade 2) and non-gangrenous (uncomplicated) appendicitis (=AAST Grade 1), respectively. The independent predictive factors of gangrenous appendicitis included a CT value of ≥24 HU, an appendiceal diameter of ≥12 mm, the presence of cecal mucosal edema, and a C-reactive protein level of ≥5.4 mg/dL. The scoring model, based on these four independent predictors, ranged from 0 to 4. The probability values of gangrenous appendicitis were 0%, 15%, and 97% in the low (0)-, moderate (1, 2)-, and high (3, 4)-risk categories, respectively. Conclusion: Our scoring model may assist in decision-making concerning emergency surgery and appendicitis management.