bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio exploration of low‐lying electronic states of linear and bent MNX+ (M = Ca, Sr, Ba, Ra; X = O, S, Se, Te, Po) and their origins
Authors: Ariyarathna Isuru R.
Published: July 2024

High‐level multireference and coupled cluster quantum calculations were employed to analyze low‐lying electronic states of linear‐MNX+ and side‐bonded‐M[NX]+ (M = Ca, Sr, Ba, Ra; X = O, S, Se, Te, Po) species. Their full potential energy curves (PECs), dissociation energies (Des), geometric parameters, excitation energies (Tes), and harmonic vibrational frequencies (ωes) are reported. The first three chemically bound electronic states of MNX+ and M[NX]+ are 3∑−, 1Δ, 1∑+ and 3A″, 1A′, 1A″, respectively. The 3∑−, 1Δ, 1∑+ of MNX+ originate from the M+(2D) + NX(2Π) fragments, whereas the 3A″, 1A′, 1A″ states of M[NX]+ dissociate to M+(2S) + NX(2Π) as a result of avoided crossings. The MNX+ and M[NX]+ are real minima on the potential energy surface and their interconversions are possible. The M2+NX−/M2+[NX]− ionic structure is an accurate representation for their low‐lying electronic states. The Des of MNX+ species were found to depend on the dipole moment (μ) of the corresponding NX ligands and a linear relationship between these two parameters was observed.
An improved DIIS method using a versatile residual matrix to accelerate SCF starting from a crude guess
Authors: Hu Linping , Sarwono Yanoar Pribadi , Ding Yonglong , He Fang , Zhang Rui‐Qin
Published: July 2024

The minimization of the commutator of the Fock and density matrices as the error matrix in the direct inversion of the iterative subspace (CDIIS) developed by Pulay is a powerful self‐consistent field (SCF) acceleration technique for the construction of optimum Fock matrix, if initiated with a fair initial guess. In this work, we present an alternative minimized error matrix to the commutator in the CDIIS, namely the residual or the gradient of the energy‐functional for a Slater determinant subject to the orthonormality constraints among orbitals, representing the search for a newly improved Fock matrix in the direction of the residual in the direct inversion of the iterative subspace (RDIIS). Implemented in the computational chemistry package GAMESS, the RDIIS is compared with the standard CDIIS and the second order SCF orbital optimization (SOSCF) for tested molecules started with a crude guess. As a result, the RDIIS stably and efficiently performs the SCF convergence acceleration. Furthermore, the RDIIS is considerably independent on the subspace size with the concentrated linear coefficients accounting proportionally for the Fock matrices close to the current iteration.
Identification and characterization of RAC1‐related immune and prognostic subtypes of hepatocellular carcinoma
Authors: Wang Wei , Xia Hui , Feng Pei , Dai Bin
Published: July 2024

Background

Hepatocellular carcinoma (HCC) is a malignant tumor with significant variability in prognosis among patients. Ras‐related C3 botulinum toxin substrate 1 (RAC1) is a key focus in the area of cancer research. However, the molecular mechanisms of RAC1 in HCC remain incompletely elucidated.

Materials and methods

In this study, bioinformatics analysis was used, and public databases were used to obtain information about HCC cases. The samples were categorized into two groups of high and low expression based on the expression level of RAC1 gene. The limma package was used to calculate the differentially expressed genes between the two groups, and univariate Cox regression analysis was used to screen the prognostic related factors. Consensus clustering analysis was performed using the ConsensusClusterPlus package to identify molecular subtypes of HCC patients. Immune cell infiltration and ESTIMATE scores were assessed using the single sample gene set enrichment analysis and ESTIMATE algorithms. The sensitivity of different isoforms to chemotherapeutic agents was predicted by the oncoPredict package. Finally, we also performed cell function experiments to validate the biological role of RAC1 in vitro. Initially, we classified patients into high and low expression groups based on RAC1 gene expression levels and identified 195 up‐regulated genes and 107 down‐regulated genes. Through univariate Cox regression analysis, we screened out 169 prognosis‐related factors. Furthermore, HCC patients were categorized into two subtypes. Subsequently, Kaplan–Meier survival curves showed that there was a significant difference in prognosis between the two molecular subtypes. Further analysis indicated substantial differences in gene expression levels and TIDE scores between two molecular subtypes. Moreover, these two subtypes exhibited varying sensitivity to chemotherapy drugs, as evidenced by differences in IC50 values. In addition, we found that the silence of RAC1 could effectively inhibit the migration and invasion of HCC cells in vitro.

Conclusion

This study sheds light on the molecular intricacies of RAC1 in HCC and identifies patient populations that may benefit from immunotherapeutic interventions, with potential implications for tailored treatment strategies.
“Fast but not so furious”: A condensed step‐up dosing schedule of teclistamab for relapsed/refractory multiple myeloma
Authors: Graf Kevin C. , Davis James A , Cendagorta Alyssa , Granger Katelynn , Gaffney Kelly J. , Green Kimberly , Hess Brian T , Hashmi Hamza
Published: July 2024

Teclistamab is a B‐cell maturation antigen (BCMA)‐directed bispecific T‐cell engager approved for relapsed‐refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) and Immune effector cell‐associated neurotoxicity syndrome (ICANS) are well‐documented treatment ‐related adverse events of teclistamab. The prescribing information recommends step‐up dosing on days 1, 4, and 7 with 48–72 h of inpatient observation after each dose to monitor for CRS. This leads to a more than weeklong hospital stay, adding to the cost of therapy, resource utilization, and patient inconvenience. Here, we present a single center retrospective analysis addressing the safety and utility of a condensed step‐up dosing schedule for teclistamab. All patients who were treated with teclistamab from November 2022 to August 2023 at the Medical University of South Carolina were included in the analysis. Patients received subcutaneous (SC) teclistamab with step‐up doses (0.06 and 0.3 mg/kg) separated by either 2 or 3 (48–72 h) before the administration of the first full (1.5 mg/kg) dose (days 1, 3, and 5 ‘condensed’ schedule or days 1, 4, and 7 ‘standard’ schedule, respectively). All patients were hospitalized for the two step‐up doses and first full dose of teclistamab and received pre‐medications prior to each dose. Patients could be discharged after a minimum of 24 h following the full dose, if they did not have any CRS or ICANS. Relevant data regarding incidence, severity, and onset of CRS was collected. Statistical analysis was completed to assess the probability of fever with the first full dose of teclistamab based on incidence of fever with previous doses. A total of 25 patients were included in the analysis. Twenty‐eight percent (7/25) of patients underwent the standard step up while the remaining 72% (18/25) underwent a condensed step up of teclistamab. More than half (53%, 13/25) of the patients experienced CRS during step up dosing. Grades 1 and 2 CRS occurred in 48% (12/25) and 4% (1/25) patients, respectively. Of the 13 patients that experienced CRS, 30% (4/13) fevered with the first dose, 84% (11/13) fevered with the second dose, and one patient developed fever after the third dose. The negative predictive value of being ‘fever free’ after doses 1 and 2 and remaining ‘fever free’ throughout hospitalization was 0.92. The median length of hospital stay among the 1, 3, and 5 step up group was 6 days (6–25) and 70% (14/20) of patients were discharged from the hospital within 7 days of treatment initiation. This report demonstrates the utility of a condensed step‐up schedule for teclistamab initiation. The schedule was found to be safe and reduced hospital length of stay. These results should prompt consideration of shorter hospital stays for patients who do not experience CRS and raise the possibility of outpatient administration with close observation.
Fludarabine, busulfan, and melphalan conditioning regimen in allogeneic hematopoietic stem cell transplantation for adult patients with myeloid malignancies: A multicenter retrospective study
Authors: Jiang Jieling , Li Xiaofan , Wu Dong , Lu Quanyi , Miao Kourong , Wang Houcai , Li Xiaoping , Chen Yingnian , Zhou Shiyuan , Zhou Yali , Liao Guiping , Jiang Chuanhe , Yuan Xiaohong , Zhao Youshan , Chang Chunkang , Chen Jie , Zhu Han , Ma Ruye , Li Nainong , Yin Xiaolin , Wu Xiaojin , Wang Sanbin , Wang Chun , Hu Jiong
Published: July 2024

Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo‐HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS‐IB‐1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow‐up was 507 days for survivors. The 2‐year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT‐CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05‐60.03, p = 0.045; HR = 3.64, 95%CI 1.40‐9.44, p = 0.008; respectively), while post‐transplantation cyclophosphamide based graft‐versus‐host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11‐0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.
Brain Metabolite Differences in Fetuses With Cytomegalovirus Infection: A Magnetic Resonance Spectroscopy Study
Authors: Sadan Or R. , Avisdris Netanell , Rabinowich Aviad , Link‐Sourani Daphna , Krajden Haratz Karina , Garel Catherine , Hiersch Liran , Ben Sira Liat , Ben Bashat Dafna
Published: July 2024

Background

Cytomegalovirus (CMV) is the most common intrauterine infection and may be associated with unfavorable outcomes. While some CMV‐infected fetuses may show gross or subtle brain abnormalities on MRI, their clinical significance may be unclear. Conversely, normal development cannot be guaranteed in CMV‐infected fetuses with normal MRI.

Purpose

To assess brain metabolite differences in CMV‐infected fetuses using magnetic resonance spectroscopy (MRS).

Study type

Retrospective.

Subjects

Out of a cohort of 149 cases, 44 with maternal CMV infection, amniocentesis results, and good‐quality MRS were included. CMV‐infected fetuses with positive polymerase chain reaction (PCR) (N = 35) were divided based on MRI results as follows: typical brain abnormalities (gross findings, N = 8), exclusive white matter hyperintense signal (WMHS) on T2‐weighted images (subtle findings, N = 7), and normal MRI (N = 20). Uninfected fetuses (negative PCR) with normal MRI were included as controls (N = 9).

Field Strength

3 T, T2‐weighted half Fourier single‐shot turbo spin‐echo (HASTE), T2‐weighted true fast imaging with steady‐state free precession (TrueFISP), T1‐ and T2*‐weighted fast low angle shot (FLASH), and 1H‐MRS single‐voxel point resolved spectroscopy (PRESS) sequences.

Assessment

MRI findings were assessed by three radiologists, and metabolic ratios within the basal ganglia were calculated using LCModel.

Statistical Tests

Analysis of covariance test with Bonferroni correction for multiple comparisons was used to compare metabolic ratios between groups while accounting for gestational age. A P‐value <0.05 was deemed significant.

Results

MRS was successfully acquired in 63% of fetuses. Substantial agreement was observed between radiologists (Fleiss' kappa [k] = 0.8). Infected fetuses with gross MRI findings exhibited significantly reduced tNAA/tCr ratios (0.64 ± 0.08) compared with infected fetuses with subtle MRI findings (0.85 ± 0.19), infected fetuses with normal MRI (0.8 ± 0.14) and controls (0.81 ± 0.15). No other significant differences were detected (P ≥ 0.261).

Conclusion

Reduced tNAA/tCr within the apparently normal brain tissue was detected in CMV‐infected fetuses with gross brain abnormalities, suggesting extensive brain damage. In CMV‐infected fetuses with isolated WMHS, no damage was detected by MRS.

Level of Evidence

3

Technical Efficacy

Stage 3
Different infliximab induction dosing regimens do not affect remission rates up to 1 year in children with Crohn's disease
Authors: Marshanski Tal , Fanous Eliana , Tal Noa , Perets Tsachi T. , Matar Manar , Weintraub Yael , Shamir Raanan , Shouval Dror S.
Published: July 2024

Objectives

Multiple studies in patients with Crohn's disease (CD) treated with anti‐tumor necrosis factor alpha agents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated (IFX) administration during induction resulted in improved outcomes.

Methods

This retrospective study included CD patients aged 5–17.9 years that were treated with IFX. We compared outcomes of patients treated during induction with 5–8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of IFX. Primary outcome was steroid‐free clinical remission by Week 52.

Results

Sixty‐eight patients were included, of whom seven discontinued IFX before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at IFX initiation. Despite receiving significantly more IFX, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn's disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5–20] vs. 5 [0–15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough IFX levels by Week 52.

Conclusion

Accelerated IFX dosing during induction did not result in improved outcomes up to 12 months follow‐up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied.
The “Halo Appearance” of Shear Wave Elastography in the Setting of Fat Necrosis
Authors: Zech John R. , Burke Christopher J. , Hoda Syed T. , Adler Ronald S.
Published: July 2024

Objective

To describe the morphologic sonographic appearances and frequency of the “halo sign” in the setting of fat necrosis on shear wave elastography (SWE).

Methods

Patients with clinically suspected fat necrosis were prospectively scanned using SWE in addition to standard gray‐scale and Doppler images. Cases were qualitatively grouped into one of three sonographic appearances: focal hypoechoic lesion with increased internal tissue stiffness (“focal stiffness”), focal hypoechoic lesion with isoechoic or hyperechoic periphery demonstrating increased tissue stiffness relative to the central hypoechoic lesion (“halo stiffness”), heterogeneously echogenic lesion with diffusely increased stiffness (“heterogeneous stiffness”).

Results

Exactly 19 patients met inclusion criteria (female n = 14; male n = 5). Shear wave velocities were recorded and retrospectively evaluated. The mean clinical follow‐up was 11.4 months (range 3.0–25.5). Lesions demonstrated higher average tissue stiffness than background tissue (overall mass shear wave velocity 3.26 m/s, background 1.42 m/s, P < .001; lesion Young's modulus 40.85 kPa vs background 7.22 kPa, P < .001). The halo sign was identified in 10/19 (55%) patients.

Conclusion

The halo sign is a potentially useful sign in the setting of fat necrosis seen in the majority of clinically suspected cases.
Theoretical study on gas‐phase reactions during chemical vapor deposition of TixAl1–xN from TiCl4, AlCl3, and NH3
Authors: Sato Noboru , Yamaguchi Jun , Koto Masahiro , Kubo Hayato , Sugiyama Takanori , Tanibuchi Takahito , Deura Momoko , Momose Takeshi , Shimogaki Yukihiro
Published: July 2024

Fcc‐TixAl1–xN (TiAlN) coatings synthesized via chemical vapor deposition (CVD) reduce cutting tool wear. Although CVD conditions reportedly influence coating quality, no quantitative guidelines are yet available. To quantitatively study the film‐forming mechanism of TiAlN CVD, the gas composition over the surface must be known. Therefore, we developed a gas‐phase elementary reaction model for TiAlN CVD derived from TiCl4/AlCl3/NH3. First, we constructed a novel thermodynamic dataset including molecules that contained both Ti and Al, and calculated the equilibrium composition. Thermal equilibrium calculations in the gas phase showed that the most stable species were AlCl3 and TiCl3 rather than TiCl4. An elementary reaction model was constructed based on the kinetics of the gas‐phase species that were generated. Kinetic analysis revealed that gas‐phase reactions were largely absent under our reactor conditions. The thermal equilibrium calculations indicated that TiCl4 may have given rise to TiCl3. Thus, other reaction pathways of TiCl4 to TiCl3 were explored. We calculated the reaction rate constants of 12 reactions of Ti species and added them to the model, which revealed that TiCl4 decomposed to TiCl3 via TiCl3NH2. Under our conditions, TiCl4 and TiCl3NH2 are the major Ti species and AlCl3 and AlCl2NH2 are the major Al species, which suggests that some of these species may form films. Unlike in the earlier reaction model, NH2 and H radicals were produced, which may have contributed to the surface reactions. For reactors with large Surface/Volume ratio of reactor, the effects of gas‐phase reactions should be considered. Our reaction model enables estimation of the partial pressures of reactor gas species and will therefore aid study of the TiAlN deposition mechanism.
Surgical Nonresponders in Zenker Diverticulum and Lower Esophageal Pathology (POUCH Collaborative)
Authors: Brown Johnathan , McCoy Nicole , Allen Jacqui , Altaye Mekibib , Amin Milan , Bayan Semirra , Belafsky Peter , DeSilva Brad , Dion Greg , Ekbom Dale , Friedman Aaron , Fritz Mark , Giliberto John Paul , Guardiani Elizabeth , Johnson Christopher , Kasperbauer Jan , Kim Brandon , Krekeler Brittany N. , Kuhn Maggie , Kwak Paul , Ma Yue , Madden Lyndsay L. , Matrka Laura , Mayerhoff Ross , Piraka Cyrus , Rosen Clark A. , Tabangin Meredith , Wahab Shaun , Wilson Keith , Wright Carter , Young VyVy N. , Postma Gregory , Howell Rebecca J.
Published: July 2024

Objective

To identify characteristics of patients who have poor improvement in symptoms following surgical management of Zenker Diverticulum (ZD).

Methods

Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgical repair of ZD between August 2017 and January 2024. Patient demographics, esophagrams, and the 10‐item Eating Assessment Tool (EAT‐10) pre‐ and post‐procedure were obtained from a REDCap database. t‐tests, Wilcoxon rank sum tests, Chi‐square or Fisher's exact tests were used to compare the characteristics. Patients with <50% improvement in their EAT‐10 scores were deemed surgical nonresponders (SNRs). Those with ≥50% improvement in their EAT‐10 scores were deemed surgical responders (SRs).

Results

A total of 184 patients were prospectively followed after undergoing either open or endoscopic surgical management. Twenty‐two patients (12%) were deemed SNRs. Preoperative presence of a hiatal hernia was statistically significant characteristic between the SNRs (63.6%) and SRs (32.1%) (p = 0.004). Size of the ZD and history of previous ZD surgery was not a significant characteristic. The length of stay and complication rate were not statistically different between the groups.

Conclusion

Coexistent esophageal pathology may lead to poor symptomatic improvement following ZD surgery. Preoperative workup of other esophageal disorders is recommended to detect likely SNRs. For SNRs, further esophageal workup may be necessary to evaluate for other esophageal causes related to poor symptomatic improvement following ZD surgery.

Level of Evidence

3 Laryngoscope, 134:4897–4902, 2024
Significance and the Use of Legumes in Developing Weaning Foods With a Balanced Nutrition—A Review
Authors: Anwar Rimsha , Borbi Makafui , Rakha Allah
Published: July 2024

Weaning is a crucial stage in an infant's development when they gradually move from being breastfed to receiving complementary foods. The typical age for introducing weaning foods is 4–6 months. This period is often characterized by rapid weight gain, so proper nutrition essential for optimal growth and development. Foods with a balanced nutrition are very important for regulating metabolism for healthy growth of children. Cereal grains and legumes have a major role in both commercial and homemade weaning foods. In developing countries, cereals and legumes are the optimal choices for producing nutrient‐dense, high‐protein, and high‐energy weaning foods. It is crucial to research and develop composite legume blends for their expanded utilization as weaning foods. Understanding the importance of complementary foods and introducing them appropriately are critical to the health and development of the infant. Furthermore, fortification and supplementation with minerals and vitamins can play a vital role in such foods. This article provides an overview of recommendations made by health authorities in relation to the onset of weaning, types/combination of foods, and infant dietary requirements and highlights the importance of including legumes in the weaning diet to address nutrient deficiencies, particularly in regions with high rates of malnutrition.
Gray‐tone appearances on 4‐hour delayed gadolinium‐enhanced magnetic resonance imaging indicate severe inner ear pathology and symptoms in sudden sensorineural hearing loss
Authors: Koizumi Toshizo , Seo Toru , Saito Kazuya , Fujita Hiroto , Kitahara Tadashi
Published: July 2024

Objective

Hybrid of reversed image of positive endolymph signal and negative image of perilymph signal (HYDROPS) in delayed gadolinium‐enhanced magnetic resonance imaging (MRI) typically depicts normal inner ear as “white‐tone” and endolymphatic hydrops as “black‐transparent” appearances, whereas ears with auditory and vestibular disorders are occasionally depicted as “gray‐tone.” This study aimed to investigate the pathological basis of sudden sensorineural hearing loss (SSNHL) patients with “gray‐tone” appearances on HYDROPS.

Methods

Delayed gadolinium‐enhanced MRI examinations were conducted on 29 subjects with unilateral SSNHL. We mainly analyzed positive perilymph image (PPI) and positive endolymph image (PEI), which were components HYDROPS.

Results

On PPI, signal intensity (SI) values extracted from the cochlear and vestibular region of interest (ROI) were higher in the SSNHL ears with dizziness/vertigo symptom at the first visit compared to the healthy ear. Additionally, the PPI/PEI enhancement pattern in the vestibule was associated with a high prevalence of hearing and vestibular deteriorations at the first visit and poor hearing improvement after treatment.

Conclusion

Enhancement on PPI/PEI may result from leakage of gadolinium into the inner ear following breakdown of the blood‐labyrinth barrier, with high SI being correlated with the amount of leakage. Particularly, a significant leakage into the endolymphatic space, defined as PPI+/PEI+, indicates severe inner ear pathology. Ultimately, we emphasize that the “gray‐tone” appearance in the inner ear on HYDROPS comprises enhancements on both PPI and PEI and propose a new classification for evaluating SSNHL Peri‐ and Endolymphatic image Enhancement pattern in Delayed gadolinium‐enhanced MRI (SPEED).

Level of Evidence

4.
Utility of chest x‐ray for tracheostomy tube placement in pediatric patients
Authors: Zhao Oliver S. , Peterson April , Patel Kalpnaben , Wilcox Lyndy
Published: July 2024

Objective

To evaluate the utility of ordering chest x‐rays after pediatric tracheostomy tube placement in identifying acute, post‐operative complications and how it impacts clinical decision‐making.

Methods

In this retrospective cohort study, we identified tracheostomies performed in 139 pediatric patients through CPT codes over a 5‐year period from 2013 to 2018. Manual chart review was performed for demographic and clinical characteristics, pre‐procedure and post‐procedure chest x‐ray interpretations, and the presence of complications. Each complication was reviewed to see if action was taken due to post‐procedure chest x‐ray findings. Multivariable logistic regression was performed to determine associations with changes in pre‐procedure versus post‐procedure chest x‐rays.

Results

In a cohort of 139 pediatric patients with pre‐procedure and post‐procedure chest x‐rays, 40 (28.8%) of patients had new significant post‐procedure chest x‐ray findings compared to pre‐procedure chest x‐ray findings. Of these 40 instances of changes in pre‐procedure versus post‐procedure chest x‐ray findings, only eight resulted in action being taken due to the observed findings. Among these eight instances of action being taken, only one instance involved in invasive action being taken with a bronchoscopy. With multivariable regression analysis, patient age, race, gender, and the presences of genetic syndromes, were not found to be significant risk factors in predicting changes in pre‐procedure versus post‐procedure chest x‐ray.

Conclusion

In our study, post‐procedure chest x‐ray after tracheostomy tube placement did not significantly impact clinical decision making. It may be worth reconsidering the value in routine chest x‐rays after tracheostomy tube placement in pediatric patients.
Transverse Inscription of Silicon Waveguides by Picosecond Laser Pulses
Authors: Blothe Markus , Alberucci Alessandro , Alasgarzade Namig , Chambonneau Maxime , Nolte Stefan
Published: July 2024

In this work, picosecond laser inscription of segmented waveguides in crystalline silicon based on a deterministic single‐pulse modification process is demonstrated. Pulses of 43 ps duration at 1.55 wavelength are used to transversely inscribe periodic structures with a pulse‐to‐pulse pitch of ≈2 . Infrared shadowgraphy images and Raman spectroscopy measurements indicate that the modifications exhibit a spherical shape. Characterization of waveguide performance at 1.55  for various pulse energies and periods is carried out. Direct comparison with numerical simulations confirms the presence of graded index waveguides, encompassing a micrometer core size and a maximum refractive index change of . This short‐pulse inscription approach can pave the way for 3D integrated photonic devices in the bulk of silicon.
Chemical space exploration with Molpher: Generating and assessing a glucocorticoid receptor ligand library
Authors: Agea M. Isabel , Čmelo Ivan , Dehaen Wim , Chen Ya , Kirchmair Johannes , Sedlák David , Bartůněk Petr , Šícho Martin , Svozil Daniel
Published: July 2024

Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery of new biologically active compounds. In this study, we present a detailed analysis of the chemical library of potential glucocorticoid receptor (GR) ligands generated by the molecular generator, Molpher. To generate the targeted GR library and construct the classification models, structures from the ChEMBL database as well as from the internal IMG library, which was experimentally screened for biological activity in the primary luciferase reporter cell assay, were utilized. The composition of the targeted GR ligand library was compared with a reference library that randomly samples chemical space. A random forest model was used to determine the biological activity of ligands, incorporating its applicability domain using conformal prediction. It was demonstrated that the GR library is significantly enriched with GR ligands compared to the random library. Furthermore, a prospective analysis demonstrated that Molpher successfully designed compounds, which were subsequently experimentally confirmed to be active on the GR. A collection of 34 potential new GR ligands was also identified. Moreover, an important contribution of this study is the establishment of a comprehensive workflow for evaluating computationally generated ligands, particularly those with potential activity against targets that are challenging to dock.
Stability analysis for wave equations with variable exponents and acoustic boundary conditions
Authors: Park Sun‐Hye , Kang Jum‐Ran
Published: July 2024

In this paper, we consider a wave equation with nonlinearities of variable exponents and acoustic boundary conditions. Using the multiplier method, we establish general stability results to the equation when the damping term has a time‐dependent coefficient and the exponent has extended range.
Approximation error estimates by noise‐injected neural networks
Authors: Akiyama Keito
Published: July 2024

One‐hidden‐layer feedforward neural networks are described as functions having many real‐valued parameters. Approximation properties of neural networks are established (universal approximation property), and the approximation error is related to the number of parameters in the network. The essentially optimal order of approximation error bounds was already derived in 1996. We focused on the numerical experiment that indicates the neural networks whose parameters contain stochastic perturbations gain better performance than ordinary neural networks and explored the approximation property of neural networks with stochastic perturbations. In this paper, we derived the quantitative order of variance of stochastic perturbations to achieve the essentially optimal approximation order and verified the justifiability of our theory by numerical experiments.
Improvement of medication adherence for desmopressin by adjusting the prescription dosage in male patients with overactive bladder: A claims database analysis
Authors: Tsubouchi Kazuna , Maeda Toshiki , Emoto Taiki , Aoyagi Chikao , Matsuoka Wataru , Yamazaki Fumihiro , Nakagawa Chizuru , Fukuhara Yuichiro , Tominaga Kosuke , Gunge Naotaka , Miyazaki Takeshi , Okabe Yu , Matsuzaki Hiroshi , Nakamura Nobuyuki , Arima Hisatomi , Haga Nobuhiro
Published: July 2024

Objectives

Desmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence.

Methods

Patients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan–Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin.

Results

The study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high‐adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC.

Conclusion

Desmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.
Dopamine production in neurotensin receptor 1 neurons is required for diet‐induced obesity and increased day eating on a high‐fat diet
Authors: Farahmand Firozeh , Sidikpramana Michael , Gomez Alyssa R. , Rivera Luis J. , Trzeciak Jacqueline R. , Sharif Sarah , Tang Qijun , Leinninger Gina M. , Güler Ali D. , Steele Andrew D.
Published: July 2024

Objective

This study aimed to determine a dopaminergic circuit required for diet‐induced obesity in mice.

Methods

We created conditional deletion mutants for tyrosine hydroxylase (TH) using neurotensin receptor 1 (Ntsr1) Cre and other Cre drivers and measured feeding and body weight on standard and high‐fat diets. We then used an adeno‐associated virus to selectively restore TH to the ventral tegmental area (VTA) Ntsr1 neurons in conditional knockout (cKO) mice.

Results

Mice with cKO of Th using Vglut2‐Cre, Cck‐Cre, Calb1‐Cre, and Bdnf‐Cre were susceptible to obesity on a high‐fat diet; however, Ntsr1‐Cre Th cKO mice resisted weight gain on a high‐fat diet and did not experience an increase in day eating unlike their wild‐type littermate controls. Restoration of TH to the VTA Ntsr1 neurons of the Ntsr1‐Cre Th cKO mice using an adeno‐associated virus resulted in an increase in weight gain and day eating on a high‐fat diet.

Conclusions

Ntsr1‐Cre Th cKO mice failed to increase day eating on a high‐fat diet, offering a possible explanation for their resistance to diet‐induced obesity. These results implicate VTA Ntsr1 dopamine neurons as promoting out‐of‐phase feeding behavior on a high‐fat diet that could be an important contributor to diet‐induced obesity in humans.
Megaprojects from the lens of business and management studies: A systematic literature review
Authors: Cottafava Dario , Corazza Laura , Shams Esfandabadi Zahra , Torchia Daniel
Published: July 2024

Megaprojects serve as the foundation of societal progress, providing essential infrastructure for a country's development and meeting its societal needs. There is a growing interest within the academic community to untangle the complex nature of megaprojects. This study conducts a comprehensive systematic literature review on megaprojects from the perspective of business, management, and accounting studies to provide a general map of the research conducted in this field and to highlight gaps for future research. The findings reveal thematic areas, including (i) sustainable development and decision‐making, (ii) governance approach, (iii) project management, (iv) risk assessment, and (v) economic and social effects/social responsibility. Moreover, identified gaps encompass limited consideration of the use/operation and end‐of‐life phases, inadequate evaluation of environmental and social impacts in economic terms, insufficient focus on sustainability reporting, inclusive governance, and using novel methodologies for complex system analysis in the field of megaprojects.
Cultural stewardship in urban spaces: Reviving Indigenous knowledge for the restoration of nature
Authors: Walker Erana , Jowett Tim , Whaanga Hēmi , Wehi Priscilla M.
Published: July 2024

Relationships to nature are important for the health and well‐being of peoples globally and should be actively protected. Indigenous Māori people in Aotearoa New Zealand recognize this important relationship to nature through narratives of lineage and express this through concepts such as kaitiakitanga; a cultural place‐based practice of stewardship that intertwines relationships of responsibility between people, nature and culture. However, many Māori now live outside of tribal areas in urban settings, putting relationships with nature into question.

We asked how urban Māori people practice kaitiakitanga, and what factors might predict flourishing relationships with nature. We surveyed 214 urban Māori who shared their perceptions of kaitiakitanga, cultural practices and restoration activities. The data were analysed by identifying qualitative themes and using linear mixed effect models.

Māori who were exposed to kaitiakitanga as children were more likely to attend marae and family restoration activities, and less likely to attend events led by local councils. Pressingly, young people in urban areas were more at risk of losing cultural knowledge and opportunities to practice cultural practices in urban areas. Age, distance from tribal area and early exposure all affected decision‐making and expression of kaitiakitanga in urban areas.

Knowledge associated with kaitiakitanga can create inclusive and effective urban restoration activities. We suggest that partnership between Māori groups including local marae, and local councils, may provide accessible, best practice urban restoration models that attract local Māori and act to support cultural knowledge, in turn encouraging diverse pathways to nature restoration to develop in urban areas. Likewise, such partnerships will ensure that Māori in cities are supported to express and maintain cultural knowledge and practice into the future.

Read the free Plain Language Summary for this article on the Journal blog.
Informing parents of newborns with sickle cell trait detected at neonatal screening: A northern France experience
Authors: Freppel Malo , Mention Karine , Renom Gilles , Lambilliotte Anne , Barbati Mélissa
Published: July 2024

Neonatal screening for sickle cell disease (SCD) in France, targeted since 1995, indirectly detects newborns with sickle cell trait (SCT). Information about carrier status must be communicated to families in accordance with the 2006 National Consultative Ethics Committee recommendations; however, no national protocol for this exists. In the departments of Nord and Pas‐de‐Calais, the Regional Neonatal Screening Center transmits this information through a general practitioner (GP). This study aimed to assess the success rate of local practices in transmitting SCT information to parents. The secondary objectives included explaining transmission failures, evaluating post‐information couple screening rates, and conducting a nationwide evaluation of SCT information dissemination. In this retrospective, multicenter study, family doctors were surveyed regarding newborns screened for SCT between January 1 and December 31, 2020, in the Nord and Pas‐de‐Calais departments. Among the 260 screened newborns, 197 were eligible for analysis. Results showed that 31.2% of newborns with SCT had their GP definitively sharing information with their parents. Based on this information, subsequent parental screening accounted for 13.6% of cases. The reasons cited by the GP for failing to convey information included elusive families (52.5%), unfamiliarity or refusal of the role (35%), limited SCD knowledge (25%), and ethical considerations (12.5%). This study highlights the difficulty and heterogeneity in transmitting carrier status information to parents of newborns with SCT. Our findings could serve as a foundation for the development of new methods for information transmission, given the generalization of neonatal screening for SCD by the French National Authority for Health.
Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study
Authors: Emiralioğlu Nagehan , Çakır Banu , Sertçelik Ahmet , Yalçın Ebru , Kiper Nural , Şen Velat , Altıntaş Derya Ufuk , Serbes Mahir , Çokuğraş Haluk , Kılınç Ayşe Ayzıt , Başkan Azer Kılıç , Hepkaya Evrim , Yazan Hakan , Türel Özden , Kafi Hale Molla , Yılmaz Aslı İmran , Ünal Gökçen , Çağlar Tuğçe , Damadoğlu Ebru , Irmak İlim , Demir Esen , Öztürk Gökçen , Bingöl Ayşen , Başaran Erdem , Sapan Nihat , Aslan Ayşe Tana , Asfuroğlu Pelin , Harmancı Koray , Köse Mehmet , Hangül Melih , Özdemir Ali , Tuğcu Gökçen , Polat Sanem Eryılmaz , Özcan Gizem , Gayretli Zeynep Gökçe , Keskin Özlem , Bilgiç Sevgi , Yüksel Hasan , Özdoğan Şebnem , Topal Erdem , Çaltepe Gönül , Can Demet , Ekren Pervin Korkmaz , Kılıç Mehmet , Süleyman Ayşe , Eyüboğlu Tuğba Şişmanlar , Cinel Güzin , Pekcan Sevgi , Çobanoğlu Nazan , Çakır Erkan , Özçelik Uğur , Doğru Deniz
Published: July 2024

Background

The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1.

Methods

A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow‐up was extracted from the national CF registry for years 2017–2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors.

Results

A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was −0.97% (95% confidence interval [CI] = −0.02 to −1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40–69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26–2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06‐8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort.

Conclusions

This data analysis recommends close follow‐up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.
EFG‐CS: Predicting chemical shifts from amino acid sequences with protein structure prediction using machine learning and deep learning models
Authors: Gu Xiaotong , Myung Yoochan , Rodrigues Carlos H. M. , Ascher David B.
Published: July 2024

Nuclear magnetic resonance (NMR) crystallography is one of the main methods in structural biology for analyzing protein stereochemistry and structure. The chemical shift of the resonance frequency reflects the effect of the protons in a molecule producing distinct NMR signals in different chemical environments. Apprehending chemical shifts from NMR signals can be challenging since having an NMR structure does not necessarily provide all the required chemical shift information, making predictive models essential for accurately deducing chemical shifts, either from protein structures or, more ideally, directly from amino acid sequences. Here, we present EFG‐CS, a web server that specializes in chemical shift prediction. EFG‐CS employs a machine learning‐based transfer prediction model for backbone atom chemical shift prediction, using ESMFold‐predicted protein structures. Additionally, ESG‐CS incorporates a graph neural network‐based model to provide comprehensive side‐chain atom chemical shift predictions. Our method demonstrated reliable performance in backbone atom prediction, achieving comparable accuracy levels with root mean square errors (RMSE) of 0.30 ppm for H, 0.22 ppm for Hα, 0.89 ppm for C, 0.89 ppm for Cα, 0.84 ppm for Cβ, and 1.69 ppm for N. Moreover, our approach also showed predictive capabilities in side‐chain atom chemical shift prediction achieving RMSE values of 0.71 ppm for Hβ, 0.74–1.15 ppm for Hδ, and 0.58–0.94 ppm for Hγ, solely utilizing amino acid sequences without homology or feature curation. This work shows for the first time that generative AI protein models can predict NMR shifts nearly comparable to experimental models. This web server is freely available at https://biosig.lab.uq.edu.au/efg_cs, and the chemical shift prediction results can be downloaded in tabular format and visualized in 3D format.
DrugDomain: The evolutionary context of drugs and small molecules bound to domains
Authors: Medvedev Kirill E. , Schaeffer R. Dustin , Grishin Nick V.
Published: July 2024

Interactions between proteins and small organic compounds play a crucial role in regulating protein functions. These interactions can modulate various aspects of protein behavior, including enzymatic activity, signaling cascades, and structural stability. By binding to specific sites on proteins, small organic compounds can induce conformational changes, alter protein–protein interactions, or directly affect catalytic activity. Therefore, many drugs available on the market today are small molecules (72% of all approved drugs in the last 5 years). Proteins are composed of one or more domains: evolutionary units that convey function or fitness either singly or in concert with others. Understanding which domain(s) of the target protein binds to a drug can lead to additional opportunities for discovering novel targets. The evolutionary classification of protein domains (ECOD) classifies domains into an evolutionary hierarchy that focuses on distant homology. Previously, no structure‐based protein domain classification existed that included information about both the interaction between small molecules or drugs and the structural domains of a target protein. This data is especially important for multidomain proteins and large complexes. Here, we present the DrugDomain database that reports the interaction between ECOD of human target proteins and DrugBank molecules and drugs. The pilot version of DrugDomain describes the interaction of 5160 DrugBank molecules associated with 2573 human proteins. It describes domains for all experimentally determined structures of these proteins and incorporates AlphaFold models when such structures are unavailable. The DrugDomain database is available online: http://prodata.swmed.edu/DrugDomain/.