bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Fibrosis‐4 index and vibration‐controlled transient elastography‐derived liver stiffness measurement for patients with metabolic dysfunction‐associated steatotic liver disease in health check‐up
Authors: Ogawa Yuji , Tomeno Wataru , Imamura Yasushi , Baba Masaru , Ueno Takato , Kobayashi Takashi , Iwaki Michihiro , Nogami Asako , Kessoku Takaomi , Honda Yasushi , Notsumata Kazuo , Fujikawa Hirotoshi , Kaai Megumi , Imajo Kento , Kawanaka Miwa , Hyogo Hideyuki , Hisatomi Mitsurou , Takeuchi Mamiko , Hakamada Taku , Honda Takashi , Tatsuta Miwa , Morishita Asahiro , Mikami Shigeru , Furuya Ken , Manabe Noriaki , Kamada Tomoari , Kawaguchi Takumi , Yoneda Masato , Saito Satoru , Nakajima Atsushi
Published: October 2024

Aims

The multisociety consensus nomenclature has introduced steatotic liver disease (SLD) with diverse subclassifications, which are metabolic dysfunction‐associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol‐associated steatotic liver disease (MetALD), alcohol‐associated liver disease (ALD), specific etiology, and cryptogenic. We investigated their prevalence, as per the new definition, in individuals undergoing health check‐ups. Additionally, we analyzed the distribution of Fibrosis‐4 (FIB‐4) index and vibration‐controlled transient elastography (VCTE)‐derived liver stiffness measurement (LSM) for MASLD.

Methods

In this cross‐sectional study, 6530 subjects undergoing a health check‐up in Japan were included. Conventional B‐mode ultrasound was carried out on all 6530 subjects, and those with MASLD underwent VCTE.

Results

The prevalence of SLD was 39.5%, comprising MASLD 28.7%, MetALD 8.6%, ALD 1.2%, specific etiology SLD 0.3%, and cryptogenic SLD 0.7%. Subjects with VCTE‐derived LSM ≥8 kPa constituted 2.1% of MASLD. FIB‐4 ≥1.3 showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value for diagnosing VCTE‐derived LSM ≥8 kPa were 60.6%, 77.0%, 5.3%, and 98.9%, respectively. The referral rate to specialists was 23.8% using FIB‐4 ≥1.30. “FIB‐4 ≥1.3 in subjects <65 years and FIB‐4 ≥2.0 in subjects ≥65 years” showed higher PPV (6.7%) and lower referral rate (17.1%) compared with FIB‐4 ≥1.3, but the sensitivity (54.5%) did not show adequate diagnostic capability as a noninvasive test for diagnosing VCTE‐derived LSM ≥8 kPa.

Conclusions

Acknowledging the selection bias in hepatology centers, we undertook this prospective health check‐up study. Although the FIB‐4 index proves to be a convenient marker, it might not perform well as a primary screening tool for liver fibrosis in the general population (UMIN Clinical Trials Registry No. UMIN000035188).
Persistent acute kidney injury: Postoperative impact and predictors in patients undergoing liver resection
Authors: Doi Shunsuke , Yasuda Satoshi , Nagai Minako , Nakamura Kota , Matsuo Yasuko , Terai Taichi , Kohara Yuichiro , Sakata Takeshi , Sho Masayuki
Published: October 2024

Aim

Persistent acute kidney injury (AKI) has not been investigated in patients undergoing liver resection. We aimed to identify the predictors of persistent AKI, its effect on postoperative outcomes and long‐term renal function in patients following liver resection, and its impact on survival in patients with hepatocellular carcinoma (HCC).

Methods

We examined 990 patients who underwent liver resection, including a subgroup analysis of 384 patients with curative resection for initial HCC. Persistent AKI was defined as residual impairment of serum creatinine ≥ 0.3 mg/dL or ≥50% from baseline 1 month after surgery.

Results

The persistent AKI group had significantly worse postoperative outcomes, including overall morbidity, major morbidity, longer hospital stay, and 90‐day mortality. In the subgroup analysis of patients with HCC, persistent AKI was associated with a significantly poorer overall survival (OS) rate (p < 0.001), and the multivariate analysis confirmed persistent AKI as an independent poor prognostic factor for OS (p = 0.005). The long‐term postoperative estimated glomerular filtration rate decline was significantly greater in the persistent AKI group than in the no AKI and transient AKI groups (p < 0.001 for both). Chronic kidney disease, albumin–bilirubin grade ≥2, and anatomical resection were independent predictors of persistent AKI (p = 0.001, p = 0.039, and p = 0.015, respectively).

Conclusions

Persistent AKI adversely affects postoperative outcomes and long‐term renal function in patients undergoing liver resection. Furthermore, it is associated with poor prognosis in patients with HCC. Therapeutic strategies to prevent persistent AKI are critical for improving postoperative outcomes in these patients.
Mechanical and dielectric properties of porous Si3N4 ceramics prepared by modified water‐based gel casting
Authors: Zhang Heng , Yao Dongxu , Xia Yongfeng , Zeng Yu‐Ping
Published: October 2024

Porous Si3N4 ceramics were prepared using the low‐toxicity monomer HEMA (2‐hydroxyethyl methacrylate) via a modified gel casting method. The rheological properties of Si3N4 slurries were investigated. Triethanolamine with high activity was used as a catalyst and modifier for gelation reactions, effectively improving the curing rate and suppressing the inherent surface oxygen inhibition in such process systems. With an increase in solid loading of the slurry, the drying shrinkage (12.3% to 5.4%) significantly decreased, while the green body density (44.0%–49.0%) and flexural strength (9.65–16.46 MPa) increased, demonstrating an excellent mechanical strength. After sintering at 1700°C, the porous Si3N4 ceramics prepared with 24–36 vol% solid loading slurry exhibited a flexural strength of 144.39–193.66 MPa and a porosity of 55.8% to 49.0%. The dielectric constant and loss tangent at 30 GHz ranged from 2.88 to 3.38 and 1.17–1.56 × 10−3, respectively. These ceramics show promising potential applications in high‐performance structural ceramics and high‐temperature wave‐transparent materials.
Antimicrobial effects of a multimodal wound matrix against methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa in an in vitro and an in vivo porcine wound model
Authors: Gil Joel , Solis Michael , Strong Ryan , Cassagnol Roger , Jozic Ivan , Davis Stephen C.
Published: October 2024

Chronic non‐healing wounds pose significant challenges due to an elevated inflammatory response caused in part by bacterial contamination (Physiol Rev. 2019;99:665). These wounds lead to billions being spent in the health care system worldwide (N Engl J Med. 2017;376:2367, Int J Pharm. 2014;463:119). We studied the in‐vitro and in‐vivo antimicrobial effects of a multimodal wound matrix (MWM) against two common wound pathogens, Methicillin‐Resistant Staphylococcus aureus (MRSA USA300) and Pseudomonas aeruginosa ATCC 27312 (PA27312) (Int Wound J. 2019;16:634). The in‐vitro study conducted was a zone of inhibition test with the two microbes at 104 Log CFU/mL inoculated on Tryptic soy agar with 5% sheep blood (TSAII) plates. Treatments used were MWM, Mupirocin (Positive control for MRSA), Silver Sulfadiazine (Positive Control for PA), Petrolatum and Sterile Saline (both serving as Negative Controls). Treatments were allowed to diffuse into the agar for 3 h and then were incubated for 24 h at 37°C. The in‐vivo study utilized a deep dermal porcine wound model (22 × 22 × 3 mm) created on six animals. Three animals were inoculated with MRSA USA300 and the other three with PA27312 with each allowing a 72‐h biofilm formation. After 72 h, baseline wounds were assessed for bacterial concentration and all remaining wounds were treated with either MWM alone, Silver Treatment or Untreated Control. Wounds were assessed on days 4, 8 and 12 after treatment application for microbiological analysis. In‐vitro, MWM exhibited significant inhibition of MRSA USA300 and PA27312 growth when compared to negative controls (p ≤ 0.05). Likewise, in‐vivo, the MWM‐treated wounds exhibited a significant (p ≤ 0.05) bacterial reduction compared to all other treatment groups, especially on days 8 and 12 for both pathogens. MWM demonstrated promise in addressing colonized wounds with biofilms. Additional studies on MWM's benefits and comparisons with existing treatments are warranted to optimize wound care strategies (Adv Wound Care. 2021;10:281).
Evaluation of the efficacy, safety and satisfaction rates of platelet‐rich plasma, non‐cross‐linked hyaluronic acid and the combination of platelet‐rich plasma and non‐cross‐linked hyaluronic acid in patients with burn scars treated with fractional CO2 laser: A randomized controlled clinical trial
Authors: Roohaninasab Masoumeh , Jafarzadeh Alireza , Sadeghzadeh‐Bazargan Afsaneh , Zare Sona , Nouri Maryam , Nilforoushzadeh Mohammad Ali , Behrangi Elham
Published: October 2024

Skin scarring can result from burns, injuries, stretch marks and acne, leading to cosmetic and functional difficulties. Treatments for burn scars encompass a range of options, such as lasers, corticosteroid injections, surgery and regenerative techniques such as platelet‐rich plasma (PRP). Hyaluronic acid‐based products offer skin hydration and shield against aging effects. A study is being conducted to evaluate how effective PRP injection, hyaluronic acid and their combination improve burn scars and their effects on quality of life and potential disabilities. In our study, PRP and non‐cross‐linked hyaluronic acid treatments were compared in 10 individuals with burn scars between 2022 and 2023. Patients received CO2 fractional laser treatment followed by injections in scar areas. Evaluations included the Vancouver scar scale (VSS), biometric assessments, ultrasounds and satisfaction ratings. Two therapy sessions were conducted at 1‐month interval, and assessments were done before treatment, 1 month after the first session, and 3 months after the first session. Biometric assessments showed significant improvements in various parameters (tewametry, corneometry, erythema index, melanin index, cutometry, thickness and density) in the intervention groups compared to the placebo group (p <0.05). PRP‐non‐cross‐linked hyaluronic acid, PRP and non‐cross‐linked hyaluronic acid treatments exhibited the best clinical responses with significant differences between groups (p <0.05). Dermal thickness did not show significant improvement during treatment sessions, and changes among subjects were not significantly different. The colorimetry parameter improved in all groups except the placebo group, with no significant difference between intervention groups. The VSS significantly decreased in all treatment groups except the placebo group. PRP, non‐cross‐linked hyaluronic acid and especially the combination of these two treatment options are very effective in treating burn scars.
Phase equilibria in the ZrO2–YO1.5–NbO2.5 system at 1300°C and high‐temperature experiments in the ZrO2–YNbO4 subsystem
Authors: Tan Xiwen , Liu Chuanqi , Luo Peide , Zhao Dan , Zhang Fan
Published: October 2024

Phase equilibria in the ZrO2–YO1.5–NbO2.5 system were experimentally studied at 1300°C, and a comparison with the existing ZrO2–YO1.5–TaO2.5 (ZYTO) was conducted. Ternary fluorite phases on the Y:Nb > 1 side extend from binary ZrO2‐YO1.5 to YO1.5–NbO2.5 system, generating a continuous solid solution region. Furthermore, it was observed that three phases of M‐YNbO4, fluorite, and m‐ZrO2 were in equilibrium. On the Y:Nb < 1 side, two three‐phase equilibrium regions were measured, namely M‐YNbO4+m‐ZrO2+O‐Nb2Zr6O17 and h‐Nb2O5+O‐Nb2Zr6O17+M‐YNbO4. The tetragonal YNbO4 and ZrO2 phases both extend nearly along with Y:Nb = 1. The t‐ZrO2 phases with slightly lower stabilizer content were found to transform into their monoclinic polymorph during the cooling process. However, in the ZrO2–YNbO4 subsystem, the tetragonal ZrO2 was nontransformable due to larger YO1.5 and NbO2.5 co‐dopants, and the maximum solubility is about 18.1 mol%. Upon cooling, the tetragonal YNbO4 phase, even with the maximum ZrO2 content, is transformable to monoclinic form. The maximum solubility of ZrO2 in YNbO4 is determined to be about 20.7 mol%. Finally, the high‐temperature liquidus in the ZrO2–YNbO4 system was first determined based on the cooling traces, and a vertical section diagram was proposed for further speculation. A eutectic reaction of Liquid→YNbO4+ZrO2 was discovered, and the eutectic composition and temperature were measured as 39.2ZrO2–29.2YO1.5–31.6NbO2.5 and 1813°C. This study provides the basis for thermodynamic assessment of ZrO2–YO1.5–NbO2.5 and is valuable for the design and development of the ZrO2–YO1.5–NbO2.5‐based ceramic materials.
AKR7A5 knockout promote acute liver injury by inducing inflammatory response, oxidative stress and apoptosis in mice
Authors: Shi Hui , Xu Wenda , Liu Qingling , Li Yan , Dong Silin , Zhao Zhenjun
Published: October 2024

Alcohol liver disease has become a worldwide critical health problem. The ingested alcohol could be converted into acetaldehyde or combined with free fatty acids to induce the endoplasmic reticulum oxidative stress in the liver. Coincidentally, AKR7A5 has both aldehyde detoxification and antioxidant effects. Therefore, we discuss the possible role and mechanism of AKR7A5 in the acute alcohol injury of mice liver. There were four experiment groups, the C57BL/6 mice of wild‐type mice (WT) or AKR7A5−/− mice (KO) were intragastrically administrated with saline or 50% ethanol at 14 mL/kg, respectively. Compared to the WT + alcohol group, abnormal liver function, disordered hepatic cord, severe congestion in the hepatic sinus and the space of the hepatic cord, occurrence of oxidative stress, DNA damage and different expressions of apoptosis‐related proteins were detected in the KO + alcohol group. Meanwhile, the biological process enrichment analysis showed that the down‐regulated proteins were related to the metabolism of fatty acid, the up‐regulated proteins positive regulation of reactive oxygen species metabolic process, negative regulation of coagulation and haemostasis. In conclusion, single ethanol binge combined with the absence of AKR7A5 caused more severe inflammatory response, oxidative stress, apoptosis of endogenous pathways, abnormal lipids metabolism and disordered coagulation in mice liver.
Video versus audio telehealth in safety net clinic patients: Changes by rurality and time
Authors: Larson Annie E. , Stange Kurt C. , Heintzman John , Zahnd Whitney E. , Davis Melinda M. , Harvey S. Marie
Published: October 2024

Background

Understanding the mix of video versus audio telehealth modality is critical to informing care for low‐income safety net clinic patients. Our study examined whether telehealth modality and continued use of telehealth varied by rurality and whether that changed over time.

Methods

Encounters from adults in the OCHIN national network of primary care safety net clinics were identified by encounter type (in‐person vs telehealth) and telehealth modality (video vs audio) from 4/1/2021 to 3/31/2023. Our main outcome was an interaction between patient rurality (defined using Rural Urban Commuting Area codes) and time. Linear probability models with clinic fixed effects were used to estimate predicted probabilities.

Results

The predicted probability of a telehealth visit decreased from 37.9% to 24.7% among urban patients (P <.001) and remained stable (29.5%‐29.8%; P = .82) among patients in small rural areas. By March 2023, telehealth use among patients in small rural areas was 5.1 percentage points higher than among urban patients (P = .02). The predicted probability of an audio‐only visit ranged from 63.5% to 70.5% for patients across all levels of rurality, but no significant differences by rurality or time were found.

Conclusions

Safety net clinic patients were more likely to use audio‐only than video telehealth visits. Telehealth in urban and large rural areas decreased since the first year of the pandemic. By the end of the study, patients in small rural communities used significantly more telehealth than urban patients. Elimination of reimbursement for audio telehealth visits may exacerbate existing health care inequities.
Drivers of vascular plant, bryophyte and lichen richness in grasslands along a precipitation gradient (central Apennines, Italy)
Authors: Cancellieri Laura , Sperandii Marta G. , Rosati Leonardo , Bellisario Bruno , Franceschini Cinzia , Aleffi Michele , Bartolucci Fabrizio , Becker Thomas , Belonovskaya Elena , Berastegi Asun , Biurrun Idoia , Brunetti Michele , Bückle Christoph , Che Rongxiao , Conti Fabio , Dembicz Iwona , Fanni Stefania , Fantinato Edy , Frank Dieter , Frattaroli Anna Rita , Garcia‐Mijangos Itziar , Guglielmino Adalgisa , Janišová Monika , Maestri Samuele , Magnes Martin , Potenza Giovanna , Primi Riccardo , Sobolev Nikolay , Tsarevskaya Nadezda , Vacca Andrea , Dengler Jürgen , Filibeck Goffredo
Published: October 2024

Questions

Semi‐natural grasslands in Southern Europe are biodiversity hotspots, yet their patterns of plant species richness are less studied than in Central Europe. In the Central Apennines (Italy), there are large areas of dry calcareous grasslands, across a steep gradient of mean annual precipitation (from 650 to 1350 mm within c. 30 km). We asked: How do these grasslands compare to other Palaearctic grasslands in richness levels? How do the precipitation gradient and other environmental predictors influence species richness? Does this influence differ among taxonomic groups?

Location

Submontane and lower‐montane belt of the Central Apennines (Abruzzo and Lazio, Italy).

Methods

We recorded the species richness of vascular plants and (terricolous) bryophytes and lichens in 97 plots of 10 m2, aligning them with the precipitation gradient while maintaining geological substrate and elevation similar. Mean temperature and precipitation were estimated with a high‐resolution regional model. A wide array of environmental variables (including soil properties and grazing load) were measured for each plot. Multivariate relationships within and between response and predictor variables were studied with Canonical Correlation. The relative importance of predictors on response variables was modeled with Boosted Regression Trees.

Results

The sampled grasslands were very species‐rich in the Palaearctic context. Vascular plant richness was negatively influenced by topographic heat load and soil sand content, but we did not detect a relationship with mean annual precipitation. Bryophyte richness was poorly modeled by the measured variables, although it was positively correlated with lichen richness. Lichen richness had a marked negative relationship with soil phosphorus and mean annual precipitation.

Conclusions

In Southern European semi‐natural mountain grasslands, vascular plant richness is driven more by fine‐scale edaphic factors than by precipitation gradients. In contrast, bryophyte and lichen species richness is predicted by a mixture of climatic and edaphic variables.
Professionalism lapses in health professions training: Navigating the ‘Yellow Card’ moments for transformative learning
Authors: Sibbald Matt , Sheth Urmi , Last Nicole , Keuhl Amy , McPherson Isla , Wojkowski Sarah , Bakker Dorothy , Rowland Paula
Published: October 2024

Introduction

Health professions training programmes face increasing reports of professionalism lapses, which can delay, or end, trainee progression. How programmes respond to professionalism lapses to facilitate professional identity development has not been clarified. The objective of this study is to identify factors that facilitate and impair transformations around professionalism lapses in health professions training programmes.

Methods

We conducted a qualitative study interviewing 5 faculty and 20 trainees with firsthand or secondhand experience with professionalism lapses from a range of health professions training programmes at McMaster University. Using reflexive thematic analysis, we coded verbatim transcripts informed by the lenses of social and transformative learning theories. We constructed themes through iterative and comparative analysis, seeking meaningful variation across professions and triangulating faculty and trainee perspectives.

Results

Four themes were constructed. First, lapses are in the eye of the beholder with personal definitions intersecting with institutional and situation norms. Difficulties exist in recognising and convincing trainees to respond to lapses that are perceived to be minor or subject to interpretation. Second, responses to professionalism lapses occurred within power hierarchies, which impacted how trainees reacted to the remediation process, risked superficial trainee responses to concerns and led to concerns around inequitable treatment in how standards were applied. Third, fostering transformation involves building trainee confidence, agency, trust and engagement. Focused support and advocacy for trainees can empower and promote agency in tackling disorienting lapses. Fourth, perspective shifts involve deep engagement over time, including but not limited to self‐reflection, structured discussion and seeking support.

Discussion

Identifying and addressing professionalism lapses is complex and requires nuanced and contextual exploration of personal, institutional and situational dynamics at play. By fostering environments that promote genuine reflection and dialogue and focus on building trainee confidence, agency, trust and engagement, health professions training programmes can better support trainees in navigating these complex situations and contribute to the broader goal of socialising to a professional culture and practice.
Harnessing RNA interference for the control of Fusarium species: A critical review
Authors: Liu Caihong , Kogel Karl‐Heinz , Ladera‐Carmona Maria
Published: October 2024

Fusarium fungi are a pervasive threat to global agricultural productivity. They cause a spectrum of plant diseases that result in significant yield losses and threaten food safety by producing mycotoxins that are harmful to human and animal health. In recent years, the exploitation of the RNA interference (RNAi) mechanism has emerged as a promising avenue for the control of Fusarium‐induced diseases, providing both a mechanistic understanding of Fusarium gene function and a potential strategy for environmentally sustainable disease management. However, despite significant progress in elucidating the presence and function of the RNAi pathway in different Fusarium species, a comprehensive understanding of its individual protein components and underlying silencing mechanisms remains elusive. Accordingly, while a considerable number of RNAi‐based approaches to Fusarium control have been developed and many reports of RNAi applications in Fusarium control under laboratory conditions have been published, the applicability of this knowledge in agronomic settings remains an open question, and few convincing data on RNAi‐based disease control under field conditions have been published. This review aims to consolidate the current knowledge on the role of RNAi in Fusarium disease control by evaluating current research and highlighting important avenues for future investigation.
Nasal immature teratoma in an elderly patient: Clinicopathological and epigenetic analogies with central nervous system counterparts, alongside genomic divergences
Authors: Inoue Shintaro , Takami Hirokazu , Tanaka Shota , Nomura Masashi , Takayanagi Shunsaku , Saito Yuki , Kikuta Shu , Kondo Kenji , Matsuura Reiko , Ikemura Masako , Yamazawa Sho , Matsutani Masao , Nishikawa Ryo , Matsushita Yuko , Ichimura Koichi , Saito Nobuhito
Published: October 2024

Germ cell tumors (GCTs) are categorized as gonadal or extra‐gonadal, based on the origin. Extra‐gonadal GCTs predominantly manifest within the central nervous system (CNS), mediastinum, retroperitoneum, and sacrococcygeal region. These malignancies are most frequently diagnosed in the pediatric, adolescent, and young adult demographics. Incidences of GCT within the nasal cavity are notably scarce, with only six cases documented. This report details the case of a 70‐year‐old man who presented with a left nasal mass ultimately diagnosed as immature teratoma. A remarkable aspect of this case was the detection of SMARCA4 (BRG1) loss through immunohistochemical analysis. In addition, methylation profiling aligned this case with CNS GCTs, specifically those classified as non‐germinomatous GCTs. This molecular characterization informed a tailored therapeutic strategy incorporating carboplatin and etoposide, alongside localized irradiation. This individualized treatment regimen achieved favorable outcomes, with the patient remaining recurrence free for over three years. This highlights the need for precise therapeutic approaches in the management of extragonadal GCTs, particularly those arising in atypical anatomical locations. The present case accentuates the significance of thorough diagnostic evaluations and customized treatment plans for rare GCT presentations. Further empirical and clinical investigations are warranted to enhance our understanding of and refine therapeutic protocols for such exceptional cases.
Societal Upheaval and the Contraceptive Transition
Authors: Lerch Mathias
Published: October 2024

Human development and family planning programs since the 1970s have led to a fast‐rising prevalence of modern contraceptive means at the global level. However, countries with rising but still low levels of contraceptive use experienced an increasing number of societal upheavals, including armed conflicts, sudden and high‐intensity natural disasters, as well as dramatic effects of health epidemics. This may challenge the continued diffusion of modern means of birth regulation as well as their adherent use. To better understand the role of societal upheavals in the contraceptive transition, we provide a narrative literature review of their multidimensional pathways of influence in the contraceptive decision‐making process. The review suggests four main findings. First, well‐known contemporary barriers to contraceptive use become more salient during societal upheavals. Second, historical barriers reemerge predominantly. Third, societal upheavals exert specific effects on the contraceptive transition, such as through birth replacement, the repopulation of communities, and the sexual vulnerability of girls and young women. Fourth, there are more pathways leading to a reduced (rather than a heightened) contraceptive prevalence. The conclusion discusses the implications of those insights for the contraceptive transition, provides a critical perspective of the literature, and draws avenues for future research.
Assessment of the antinociceptive effect of a single fentanyl bolus dose in children: A pharmacokinetic and pharmacodynamic analysis based on the nociception level index during sevoflurane general anesthesia
Authors: Cruzat Francisco , Ibacache Mauricio , González Alejandro , Pedemonte Juan Cristóbal , Contreras Víctor , Giordano Ady , Cortínez Ignacio
Published: October 2024

Background

The Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration.

Aims

To evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia.

Methods

Nineteen children, 5.3 (4.1–6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 μg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5‐, 15‐, and 30‐min post‐fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®.

Results

After the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) −12(−18–−6) and 100 ± 10 vs. 102 ± 10; −2(−4–−0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5–18) and 102 ± 10 vs. 91 ± 11; 11 (7–16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight‐scaled, 3‐compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect‐site equilibration half‐time of 1.69 (0.4–2.9) min. The estimated fentanyl C50 was 1.93 (0.73–4.2) ng/mL.

Conclusion

The Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception‐antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.
Assessment of accuracy of two pulse oximeters in infants with cyanotic and acyanotic congenital heart diseases
Authors: Georgiev Yordan Hristov , Neunhoeffer Felix , Hofbeck Michael , Michel Jörg
Published: October 2024

Background

Peripherally measured oxygen saturation (SpO2) may often differ from arterial oxygen saturation (SaO2), measured by co‐oximetry, especially within the lower range of oxygen saturations. This can potentially impact clinical decisions and therapy in children with congenital heart disease, as critical hypoxemia might remain unnoticed.

Aims

Our aim was to investigate the accuracy of two different pulse oximeters compared to SaO2 in infants with congenital heart diseases.

Methods

Simultaneous recordings of SpO2, measured by two different pulse oximeters (Philips IntelliVue X3 Monitor and Nellcor™ OxiMax™), were compared to SaO2 obtained by arterial blood gas analysis.

Results

A total of 153 measurements were performed in 44 infants with arterial oxygen saturation between 70 and 100%. We divided the measurements into 3 subgroups: group 1—SaO2 70.0%–85.0%, group 2—SaO2 85.1%–94.0%, group 3—SaO2 >94.1%. For Philipps, the median bias was 5.3 (IQR: 2.6–8.7) %, 2.3 (IQR: 0.9–6.0) % and 1.1 (IQR: −0.8–2.4) % in group 1, 2 and 3, respectively. For OxiMax™, the median bias was 2.7 (IQR: 0.5–5.1) %, 0.2 (IQR: −0.9–2.6) % and −0.5 (IQR: −1.3–0.6) % in group 1, 2 and 3, respectively. Regarding the accuracy of these oximeters, as evaluated with the Accuracy root mean squared index (Arms), it was 9.8 versus 4.5% in group 1, 4.5 versus 2.9% in group 2 and 2.4 versus 1.9% in group 3 for Philipps and OxiMax™, respectively.

Conclusions

In lower range saturations between 70% and 85% the accuracy of both pulse oximeters exceeded the threshold of ≤3% recommended by the Food and Drug Administration (FDA). Therefore, peripheral pulse oximetry within the lower range of oxygen saturations should be interpreted with caution in infants with congenital heart diseases, taking into consideration its limitations. Direct co‐oximetry should be the preferred method to support clinical decisions in children with cyanotic congenital heart diseases.
Adherence to ESMO guidelines on cancer pain management and their applicability to specialist palliative care centers: An observational, prospective, and multicenter study
Authors: Carbonara L. , Casale G. , De Marinis M. G. , Bosetti C. , Valle A. , Carinci P. , D'andrea M. R. , Corli O.
Published: October 2024

Introduction

Pain management in late‐stage cancer patients is a complex clinical problem. The historical guidelines were from the World Health Organization (WHO). Recently, ESMO produced guidelines consistent with 52 recommendations applicable to the entire period of disease since the pain appears.

Aim

To evaluate the appropriateness and applicability of ESMO guidelines (EGL) in advanced cancer patients admitted to palliative care.

Method

An observational, prospective, multicentric study conducted by specialist palliative care centers on cancer patients in the advanced stage. The 52 recommendations were divided into eight macro areas. The adherence levels were expressed as a percentage for each recommendation and have been broken down as high (>75%), medium (50%–75%), and low (<50%). In the case of not adhering to a recommendation, the comment was “not applicable” (NA) or not evaluable (NE).

Results

Four hundred seventy‐six patients were enrolled in the study. Thirty‐five recommendations were considered NA or NE, especially because their application took too long to achieve clinical results, given the condition of the patients. Some interesting opinions on the choice of drugs emerged. At the end of the study, pain dropped from 5.0 to 2.6, patients' satisfaction increased from 3.3 to 4.6, and quality of life improved from 4.4 to 5.5.

Conclusions

Palliative physicians' adherence to EGL was medium. The main contribution of this study was to evaluate their applicability and clinical results in far‐advanced patients assisted by palliative care. The selection of useful recommendations and expert opinions can make a contribution to clinical practice.
Treatment Adherence in Pediatric Atopic Dermatitis: A Systematic Review
Authors: Dagenet Caitlyn B. , Gawey Lauren , Davoudi Sahar , Ma Elaine , Jeong Charlotte , Atluri Swetha , Kincannon Jay M. , Hsiao Jennifer L. , Feldman Steven R. , Shi Vivian Y.
Published: October 2024

Introduction

Adherence to pediatric atopic dermatitis (AD) treatment regimens can be complex and a major challenge to optimizing treatment outcome. We aimed to review factors associated with nonadherence in pediatric AD and propose interventions to improve adherence.

Methods

PubMed and EMBASE databases were systematically searched for articles from 2000 to February 2023 related to AD and adherence, with an additional update in December 2023. Non‐human studies, reviews, commentaries, and meta‐analyses were excluded. Articles were sorted into pediatric versus adult study population based on volume. Herein, we examine the results of papers discussing adherence factors related to pediatric patients.

Results

A total of 62 studies met inclusion criteria. Thirty‐six studies surveyed patients and caregivers (N = 10,268) to identify barriers to treatment adherence. None of the included studies were specific to systemic medications. Barriers included poor caregiver quality of life, inadequate AD‐related education, topical corticosteroid (TCS) phobia, unclear therapy‐related instructions, and dissatisfaction with physician interaction. Five studies solely measured adherence using medication electronic monitoring systems, Morisky medication adherence scale, or self‐reported adherence to measure adherence to topical medications. Twenty‐one studies described interventions involving nurse‐led or web‐based education programs, text message or email reminders, and TCS education. Adherence was improved with caregiver education programs, daily text‐message reminders, eczema action plans, TCS potency “traffic light” color system, and frequent follow‐up visits.

Conclusion

Adherence to pediatric AD treatment poses a multifactorial challenge for caregivers and patients. This study provides an index of strategies to optimize adherence, as it is essential for prevention of long‐term sequela associated with AD in children. As the AD treatment landscape rapidly expands, further studies are vital to assess pediatric adherence to new topical, oral, and injectable medications.

Trial Registration

PROSPERO: CRD42023488557
Tactics of investment in couple relationship and their impact on relationship satisfaction
Authors: Bokek‐Cohen Ya'arit , Halamish‐Leshem Riki
Published: October 2024

This is a comprehensive study that aimed at identifying the effective tactics for investment in couple relationships and included the following three phases. (a) A preliminary qualitative project that collected potential ways to invest in couple relationships. (b) We identified 46 ways to invest in relationships and grouped them into six tactics using EFA, and then we validated a relational investment tactics scale. The six tactics are (1) emotional gestures, (2) material gestures, (3) personal space, (4) physical attractiveness and sex, (5) shared activities, and (6) help the partner's family and friends. (c) Finally, we evaluated the frequency of use of each of the 46 ways of relational investment among 483 respondents. Findings show that respondents who provide emotional and material gestures are involved in shared activities with their partner and help their partner's family and friends report higher marital satisfaction. We propose several practical implications based on these results.
Comparative transcriptomics and bioinformatics profiling provide insights into resistance to Fusarium wilt in melon
Authors: Zhan Ni , Wang Zhen , Zhang Yilin , Zhang Luyan , Fang Xinyu , Yan Xunyou , Wu Yanping , Li Jinghai , Li Shuqing , Shi Zhenxia , Zhao Hongbo
Published: October 2024

Melon is an important cash crop grown worldwide, with China leading the world in melon acreage. Melon wilt is becoming more common as the area under melon cultivation gradually increases. Therefore, it is crucial to understand the resistance pattern of Fusarium wilt in melons. In this work, among the four test melon cultivars, YG was highly resistant to Fusarium wilt and 1455 was disease‐resistant. However, 5657 was susceptible, while 5455 was highly susceptible to the disease. We detected 71,852 differentially expressed genes in 16 combinations, including 37,382 with up‐regulation and 3470 with down‐regulation, and we investigated 11 genes associated with resistance to Fusarium wilt through bioinformatics and transcriptome analysis. We identified two differentially expressed cinnamyl alcohol dehydrogenases (CAD) that were down‐regulated in the susceptible melon material in contrast to the resistant variety. Nine chitinase (CHT) genes were differentially expressed, with four showing up‐regulation and four showing down‐regulation in the susceptible compared to the resistant melon material. The MeloCHT genes were located on chromosomes 2, 6, 8, 11 and 12, with four of them on chromosome 8. MeloCAD1 was located on chromosome 1 and MeloCAD2 on chromosome 8. The physicochemical properties of the encoded proteins were predicted by bioinformatics, including theoretical isoelectric point, instability coefficient, relative molecular mass, lipid solubility index and hydrophilicity index. The genes encode proteins with α‐helix, extended strand, random coils and β‐turns. This study provides fundamental knowledge on the transcriptome of melons and establishes a foundation for future research on the detection and application of Fusarium wilt‐resistant genes in melons.
Genome‐wide association study reveals the genetic basis of amino acids contents variations in Peanut (Arachis hypogaea L.)
Authors: Umer Muhammad J. , Lu Qing , Huang Lu , Batool Raufa , Liu Hao , Li Haifen , Wang Runfeng , Qianxia Yu , Varshney Rajeev K. , Pandey Manish K. , Hong Yanbin , Chen Xiaoping
Published: October 2024

Peanut is a significant source of protein for human consumption. One of the primary objectives in peanut breeding is the development of new cultivars with enhanced nutritional values. To further this goal, a genome‐wide association study (GWAS) was conducted to analyze seed amino acids contents in 390 diverse peanut accessions collected worldwide, mainly from China, India, and the United States, in 2017 and 2018. These accessions were assessed for their content of 10 different amino acids. Variations in amino acids contents were observed, and arginine (Arg) was found to have the highest average value among all the amino acids quantified. The geographical distribution of the accessions also revealed variations in amino acids contents. High and positive correlation coefficients were observed among the amino acids, suggesting linked metabolic pathways or genetic regulation. A total of 88 single nucleotide polymorphisms (SNPs) spanning various chromosomes were identified, each associated with different amino acids. By using a combination of GWAS, expression anlaysis, and genomic polymorphisim comparisions, the Ahy_A09g041582 (LAC15) gene located on chromrosome A09 was identified as the key candidate which might be involved in plant growth and regulation and may alter amino acids levels. Expression analysis indicated that Ahy_A09g041582 has higher expressions in the shells and seeds than other genes located in the candidate region. This study may help with marker‐based breeding of peanuts with higher nutritional value and offers fresh insights into the genetic basis of the amino acids contents of peanuts.
Environmental disasters and ecomodernist beliefs: Insights from a quasi‐natural experiment
Authors: Sundström Aksel
Published: October 2024

This article contributes to knowledge of how environmental disasters affect ecomodernist beliefs, i.e. the view that technology can solve environmental problems. Such beliefs in the general public are key to build mass support for environmental policies relying on large‐scale scientific solutions, but their stability is poorly understood. We argue that ecomodernist beliefs are more malleable than assumed and can be altered through events that highlight risks arising from a reliance on technological solutions. This study leverages that the Fukushima‐Daiichi accident happened during the fieldwork of a 2011 public opinion survey in Israel. The analysis suggests that ecomodernist beliefs were negatively affected by this unexpected tragedy. Consistent with expectations, we report stronger impact among people with more education. We document similar effects from a controlled survey experiment in the US and Israel, suggesting that these results are generalizable. Our findings are relevant beyond rare environmental disasters as they have implications for how ecomodernist beliefs might be formed and changed.
Inflammation‐induced loss of CFTR‐expressing airway ionocytes in non‐eosinophilic asthma
Authors: Chen Ling , A. Hoefel Gabriela , Pathinayake Prabuddha S. , Reid Andrew , Pillar Amber L. , Kelly Coady , Tan HuiYing , Ali Ayesha , Kim Richard Y. , Hansbro Philip M. , Brody Steven L. , Foster Paul S. , Horvat Jay C. , Riveros Carlos , Awatade Nikhil , Wark Peter A. B. , Kaiko Gerard E.
Published: October 2024

Background and Objective

Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non‐eosinophilic asthma. Non‐eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non‐eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non‐eosinophilic asthma.

Methods

Patient‐derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air‐liquid interface. Single cell RNA‐sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma.

Results

We identified that hBECs from patients with non‐eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR‐expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic‐dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma‐like inflammatory cytokine mixture led to a reduction in ionocytes.

Conclusion

Inflammation‐induced loss of CFTR‐expressing ionocytes in airway cells from non‐eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target.

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Exiles and innovators: a survey of heretics in sixteenth‐century Europe
Authors: Burke Peter
Published: October 2024

The links between exile and innovation have often been studied in the case of the twentieth century, but much less in the case of early modern Europe – an age of some political exiles and many religious ones. This essay focuses on what has been called ‘the Reformation of the Refugees’ in the early sixteenth century. Were these exiles innovators? At a time when novelty was frequently condemned, these early Protestants were certainly accused of innovation, though they replied that all they wanted was to return to the practices of the ‘primitive church’. I argue that they did innovate, and in this survey I assess the scope of this innovation. The radicalization of individual refugees has often been discussed, but overviews are less common, including the emphasis on the role of cities in this process. The cities in which these exiles found a refuge, especially Strasbourg and Basel, encouraged debates in which new ideas were forged, exemplifying the way in which displacement could lead to changes of mind.
The potential of x‐ray virtual histology in the diagnosis of skin tumors
Authors: Saccomano Giulia , Pinamonti Maurizio , Longo Elena , Marcuzzo Thomas , Tromba Giuliana , Dreossi Diego , Brun Francesco
Published: October 2024

Background

Histopathological analysis represents the gold standard in clinical practice for diagnosing skin neoplasms. While the current diagnostic workflow has specialized in producing robust and accurate results, interpreting tissue architecture and malignant cellular morphology correctly remains one of the greatest challenges for pathologists. This paper aims to explore the prospect of applying x‐ray virtual histology to human skin tumor excisions and correlating it with the histological validation.

Materials and Methods

Seven skin biopsies containing intriguing melanoma types and pigmented skin lesions were scanned using x‐ray Computed micro‐Tomography (μCT) and then sectioned for conventional histology assessment.

Results

The tissue microarchitecture reconstructed by μCT offers detailed insights into diagnosing the malignancy or benignity of the skin lesions. Three‐dimensional reconstruction via x‐ray virtual histology reveals infiltrative patterns in basal cell carcinoma and evaluated invasiveness in melanoma. The technology enables the identification of pagetoid distributions of neoplastic cells and the assessment of melanoma depth in three dimensions.

Conclusion

Although the proposed approach is not intended to replace conventional histology, the non‐destructive nature of the sample and the clarity provided by virtual inspection demonstrate the promising impact of μCT as a valid support method prior to conventional histological sectioning. Indeed, μCT images can suggest the optimal sectioning position before using a microtome, as is commonly performed in histological practice. Moreover, the three‐dimensional nature of the proposed approach paves the way for a more accurate assessment of significant prognostic factors in melanoma, such as Breslow thickness, by considering the whole micro‐volume rather than a two‐dimensional observation.
Characterization of the Novel HLA‐C*07:01:126 Allele by Sequencing‐Based Typing
Authors: Elsermans Vincent , Visentin Jonathan , Pajot Thibault , Top Isabelle , Labalette Myriam
Published: October 2024

HLA‐C*07:01:126 differs from HLA‐C*07:01:01:01 by one nucleotide substitution in codon 328 in exon 7.
The HLA‐C*14:152 Allele Was Identified Using a Next‐Generation Sequencing Method
Authors: Kim Si‐Hwan , Yang John Jeongseok , Oh Heung‐Bum
Published: October 2024

HLA‐C*14:152 differs from HLA‐C*14:02:01:01 by a non‐synonymous nucleotide substitution in exon 5.