bluuebunny/crossref_metadata_2025 huggingface dataset:
A high‐dose, depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy has a favourable efficacy/safety ratio
Authors: Pfaar Oliver , Sager Angelika , Mösges Ralph , Worm Margitta
Published: November 2023

Background

Subcutaneous allergen immunotherapy (SCIT) with depigmented, polymerized (DPP) birch pollen extract has been marketed at doses of up to 1000 DPP units/mL since 2001. We sought to determine the dose‐dependent efficacy of a DPP birch pollen extract formulation in patients suffering from birch‐pollen‐induced allergic rhinitis or rhinoconjunctivitis with or without intermittent asthma.

Methods

A titrated conjunctival provocation test (CPT) was applied as a surrogate marker. This Phase II randomized, double‐blind, parallel‐group, dose‐ranging clinical trial was performed at 39 centres in Germany, Lithuania and Poland. After randomization to four dose‐level groups (100, 1000, 5000 and 10,000 DPP units/mL) and up‐dosing, participants received maintenance SCIT with five monthly subcutaneous injections. The primary endpoint was the proportion of patients in whom a higher concentration of birch pollen (vs. baseline) was needed to elicit a positive CPT.

Results

Three hundred forty‐three patients were included (mean (range) age: 42.6 (19–70)). The highest CPT responder rates were seen in the higher dose‐level groups. In the intention‐to‐treat analysis, the difference between the 100 and 10,000 groups was statistically significant (p = 0.0118). Although the proportion of patients with ≥1 treatment‐emergent adverse events increased with the dose, almost all these events were mild (65.6%) or moderate (18.5%).

Conclusion

Judging by the results of a CPT, the efficacy/safety ratio in SCIT appears to be favourable for a high‐dose‐level preparation of a DPP birch pollen extract.
Data‐driven evidence shows truthful caregiver histories and significant overdiagnosis of abusive head trauma
Authors: Brook Chris B.
Published: November 2023

Objective

We analyzed the veracity of caregiver‐provided histories when infants present with intracranial pathologies and abusive head trauma (AHT) is suspected.

Methods

A comparison of medical findings is made using data from 335 infants with acute intracranial pathologies and no extracranial findings associated with abuse. Two null hypotheses were tested: (1) that cases where caregivers reported accidental trauma have similar medical findings to independently witnessed accidents; and (2) that cases where caregivers reported no trauma have similar medical findings as cases where caregivers reported accidental trauma.

Results

The first null hypothesis is not rejected, corroborating caregiver histories of accidental trauma, yet such cases are diagnosed as AHT at significantly higher rates than accidents witnessed by unbiased independent observers. The second null hypothesis is rejected, corroborating caregiver histories that no trauma occurred.

Conclusions

Data suggest that caregivers can provide valuable diagnostic information when infants present with acute intracranial pathologies and suggest substantial rates of misdiagnosis of AHT.
Fractional cuckoo search invasive weed optimized neural network for data classification
Authors: Rathod Nilesh , Wankhade Sunil
Published: November 2023

The progression of organizing and classifying data components based on pre‐established criteria is known as data classification. In data classification problems, machine learning methods are frequently used. Although the ability of an algorithm to learn is essential, the recognition quality of algorithms is undoubtedly a key indicator. However, the error made in the beginning is significant, and if it is not rectified then, it causes chaos in data classification. In this research, a fractional hybrid optimization is created with a feed‐forward neural network (FFNN) for the data classification. The pre‐processing of the medical data involves the imputation of missing values and the log transformation. In the feature selection process, the chord distance and the Jaro‐Winkler distance are both employed to choose the important features. The FFNN classifier is used to classify the data, which is trained using the hybrid optimization method, namely the developed Fractional Cuckoo search Invasive Weed Optimization algorithm (FCSIWO). The fractional concept, Invasive Weed Optimization (IWO) algorithm, and Cuckoo search (CS) algorithm are combined to create the FCSIWO. When compared to existing data classification models, the developed technique achieved an optimal sensitivity of 0.9463, an optimal accuracy of 0.9440, and an optimal specificity of 0.9422.
Methodology for Good Machine Learning with Multi‐Omics Data
Authors: Coroller Thibaud , Sahiner Berkman , Amatya Anup , Gossmann Alexej , Karagiannis Konstantinos , Moloney Conor , Samala Ravi K. , Santana‐Quintero Luis , Solovieff Nadia , Wang Craig , Amiri‐Kordestani Laleh , Cao Qian , Cha Kenny H. , Charlab Rosane , Cross Frank H. , Hu Tingting , Huang Ruihao , Kraft Jeffrey , Krusche Peter , Li Yutong , Li Zheng , Mazo Ilya , Paul Rahul , Schnakenberg Susan , Serra Paolo , Smith Sean , Song Chi , Su Fei , Tiwari Mohit , Vechery Colin , Xiong Xin , Zarate Juan Pablo , Zhu Hao , Chakravartty Arunava , Liu Qi , Ohlssen David , Petrick Nicholas , Schneider Julie A. , Walderhaug Mark , Zuber Emmanuel
Published: November 2023

In 2020, Novartis Pharmaceuticals Corporation and the U.S. Food and Drug Administration (FDA) started a 4‐year scientific collaboration to approach complex new data modalities and advanced analytics. The scientific question was to find novel radio‐genomics‐based prognostic and predictive factors for HR+/HER− metastatic breast cancer under a Research Collaboration Agreement. This collaboration has been providing valuable insights to help successfully implement future scientific projects, particularly using artificial intelligence and machine learning. This tutorial aims to provide tangible guidelines for a multi‐omics project that includes multidisciplinary expert teams, spanning across different institutions. We cover key ideas, such as “maintaining effective communication” and “following good data science practices,” followed by the four steps of exploratory projects, namely (1) plan, (2) design, (3) develop, and (4) disseminate. We break each step into smaller concepts with strategies for implementation and provide illustrations from our collaboration to further give the readers actionable guidance.
The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses
Authors: da Silva Antunes Ricardo , Weiskopf Daniela , Sidney John , Rubiro Paul , Peters Bjoern , Lindestam Arlehamn Cecilia S. , Grifoni Alba , Sette Alessandro
Published: November 2023

Epitopes recognized by T cells are a collection of short peptide fragments derived from specific antigens or proteins. Immunological research to study T cell responses is hindered by the extreme degree of heterogeneity of epitope targets, which are usually derived from multiple antigens; within a given antigen, hundreds of different T cell epitopes can be recognized, differing from one individual to the next because T cell epitope recognition is restricted by the epitopes’ ability to bind to MHC molecules, which are extremely polymorphic in different individuals. Testing large pools encompassing hundreds of peptides is technically challenging because of logistical considerations regarding solvent‐induced toxicity. To address this issue, we developed the MegaPool (MP) approach based on sequential lyophilization of large numbers of peptides that can be used in a variety of assays to measure T cell responses, including ELISPOT, intracellular cytokine staining, and activation‐induced marker assays, and that has been validated in the study of infectious diseases, allergies, and autoimmunity. Here, we describe the procedures for generating and testing MPs, starting with peptide synthesis and lyophilization, as well as a step‐by‐step guide and recommendations for their handling and experimental usage. Overall, the MP approach is a powerful strategy for studying T cell responses and understanding the immune system's role in health and disease. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Generation of peptide pools (“MegaPools”)

Basic Protocol 2: MegaPool testing and quantitation of antigen‐specific T cell responses
Evaluation of salivary transferrin in patients with oral squamous cell carcinoma
Authors: Tavakoli Fatemeh , Ghavimi Mohammad Ali , Fakhrzadeh Vahid , Abdolzadeh Dorna , Afshari Aylar , Eslami Hosein
Published: November 2023

Objectives

About 94% of oral cancers are squamous cell carcinomas (OSCCs). Its occurrence is age‐related due to some factors. Salivary biomarkers have good susceptibility to OSCC's early diagnosis. Moreover, since the clinical diagnosis of advanced stages of OSCC is feasible, its prognosis is very poor.

Material and Methods

According to inclusion and exclusion criteria, 40 OSCC patients and 40 healthy people were selected, and 5 mL of saliva were prepared from each person. The quantity of saline transferrin was computed. After that, the data were analyzed.

Results

Our study results demonstrated that the mean and standard deviation of the salivary transferrin in the control group were 1.234 mL and 0.374, respectively, and in the case group, it was equal to 2.512 mL for the mean and 0.463 for the standard deviation. There was a statistically substantial difference between the mean of the salivary transferrin variable in the two study groups.

Conclusion

In conclusion, the mean concentration of salivary transferrin in the case group was higher than in the control group.
Potentilla parvifolia strongly influenced soil microbial community and environmental effect along an altitudinal gradient in central Qilian Mountains in western China
Authors: Cheng Miaomiao , Song Jinge , Li Weikun , Zhao Yiming , Zhang Gaosen , Chen Yong , Gao Haining
Published: November 2023

The Qilian Mountains (QLMs) form an important ecological security barrier in western China and a priority area for biodiversity conservation. Potentilla parvifolia is a widespread species in the mid‐high altitudes of the QLMs and has continuously migrated to higher altitudes in recent years. Understanding the effects of P. parvifolia on microbial community characteristics is important for exploring future changes in soil biogeochemical processes in the QLMs. This study found that P. parvifolia has profound effects on the community structure and ecological functions of soil microorganisms. The stability and complexity of the root zone microbial co‐occurrence network were significantly higher than those of bare soils. There was a distinct altitudinal gradient in the effect of P. parvifolia on soil microbial community characteristics. At an elevation of 3204 m, P. parvifolia promoted the accumulation of carbon, nitrogen, and phosphorus and increased sucrase activity and soil C/N while significantly improving the community richness index of fungi (p < .05) compared with that of bacteria and the relative abundance of Ascomycota. The alpha diversity of fungi in the root zone soil of P. parvifolia was also significantly increased at 3550 m altitude. Furthermore, the community similarity distance matrix of fungi showed an evident separation at 3204 m. However, at an altitude of 3750 m, P. parvifolia mainly affected the bacterial community. Potentilla parvifolia increased the bacterial community richness. This is in agreement with the findings based on the functional prediction that P. parvifolia favors the growth and enrichment of denitrifying communities at 3550 and 3750 m. The results provide a scientific basis for predicting the evolutionary trends of the effects of P. parvifolia on soil microbial communities and functions and have important implications for ecological governance in the QLMs.
First‐ever satellite tracking of Black Terns (Chlidonias niger): Insights into home range and habitat selection
Authors: McKellar Ann E. , Clements Sarah J.
Published: November 2023

Understanding animal movement across the annual cycle is critical for developing appropriate conservation plans, but the large size and high cost of tracking devices can limit the spatial and temporal resolution at which movement data can be collected, especially for small avian species. Furthermore, for species with low breeding site fidelity, the ability to obtain tracking data from small, archival tags is hindered by low recapture rates. We deployed satellite tracking devices on four adult Black Terns (Chlidonias niger), a declining waterbird with low site fidelity, to examine space use and selection of resources within individual breeding home ranges. We also provide a preliminary assessment of habitat use during fall stopover. We found that home ranges were extensive (mean 283.7 km2) and distances travelled from the nest substantially larger (up to 35 km) than previously thought (~2.5 km). Terns showed selection for wetlands and open water on the breeding grounds, but also showed selection for developed areas. This may reflect humans selecting similar landscape features for recreation and development as terns, and suggests that terns can tolerate the light degree of development (e.g. cottages, boat launches, etc.) within our study area. Despite a small sample size, this is the first study to track individual Black Terns at a high resolution with implications for conservation and wetland management practices relevant to the spatial scales at which habitat is used by the species.
Backbone ground motion model through simulated records and XGBoost machine learning algorithm: An application for the Azores plateau (Portugal)
Authors: Karimzadeh Shaghayegh , Mohammadi Amirhossein , Salahuddin Usman , Carvalho Alexandra , Lourenço Paulo B.
Published: November 2023

Azores Islands are seismically active due to the tectonic structure of the region. Since the 15th century, they have been periodically shaken by approximately 33 moderate to strong earthquakes, with the most recent one in 1998 (Mw = 6.2). Nonetheless, due to insufficient instrumental seismic data, the region lacks a uniform database of past real records. Ground motion simulation techniques provide alternative region‐specific time series of prospective events for locations with limited seismic networks or regions with a seismic gap of catastrophic earthquake events. This research establishes a local ground motion model (GMM) for the Azores plateau (Portugal) by simulating region‐specific records for constructing a homogeneous dataset. Simulations are accomplished in bedrock using the stochastic finite‐fault approach by employing validated input‐model parameters. The simulation results undergo validation against the 1998 Faial event and comparison with empirical models for volcanic and Pan‐European datasets. A probabilistic numerical technique, namely the Monte‐Carlo simulation, is employed to estimate the outcome of uncertainty associated with these parameters. The results of the simulations are post‐processed to predict the peak ground motion parameters in addition to spectral ordinates. This study uses XGBoost to circumvent the difficulties inherent to linear regression‐based models in establishing the form of equations and coefficients. The input parameters for prediction are moment magnitude (Mw), Joyner and Boore distance (RJB), and focal depth (FD). The quantification of GMM uncertainty is accomplished by analyzing the residuals, providing insight into inter‐ and intra‐event uncertainties. The outcomes demonstrate the effectiveness of the suggested model in simulating physical phenomena.
Automated cyberattack detection using optimal ensemble deep learning model
Authors: Vaiyapuri Thavavel , Shankar K. , Rajendran Surendran , Kumar Sachin , Gaur Vimal , Gupta Deepak , Alharbi Meshal
Published: November 2023

In recent times, the Industrial Internet of Things (IIoT) has developed significantly. In the application of automation, and intelligence, industrial digitalization introduced cyber risks, and the varied and complex industrial IoT platform presented a novel attack surface for network invaders. Several Intrusion Detection Systems (IDS) were advanced recently as many computer networks exposure to privacy and security threats. Availability, Data confidentiality, and integrity, the damage will happen in case of IDS prevention failure. Traditional methods were ineffective in dealing with advanced attacks. Advanced deep learning (DL) methods were designed for automatic ID and abnormal behavior detection of networks. Therefore, this article focuses on the design of Improved Reptile Search Optimization with Ensemble Deep Learning based Cybersecurity (IRSO‐EDLCS) technique in the IIoT environment. The major aim of the IRSO‐EDLCS technique lies in the accurate identification of cyberattacks in the IIoT environment. To accomplish this, the presented IRSO‐EDLCS technique performs IRSO algorithm‐based feature selection (IRSO‐FS) technique. In addition, the IRSO‐EDLCS technique performs an ensemble of three DL models namely deep belief network (DBN), bidirectional gated recurrent unit (BiGRU), and autoencoder (AE). The hyperparameter tuning process is performed by a modified gray wolf optimizer (MGWO) to enhance detection process. To exhibit the improved performance of the IRSO‐EDLCS algorithm, a wide range of simulations were performed on the benchmark database. The experimental outcomes depict the betterment of the IRSO‐EDLCS technique over other existing models.
Pinobanksin from peony seed husk: A flavonoid with the potential to inhibit the proliferation of SH‐SY5Y
Authors: Chen Wen‐Tao , Zhang Ying‐Yang , Qiang Qiang , Zou Lin‐Ling , Zou Ping , Xu Ying
Published: November 2023

Pinobanksin, as one of the flavonoids, has powerful biological activities but has been under‐recognized. In this study, we optimized the extraction method of phragmites from peony seed shells by using organic solvent extraction. The yield of PSMS was 10.54 ± 0.13% under the conditions of ethanol volume fraction 70%, extraction temperature 70°C, material–liquid ratio 1:25 g/mL, and extraction time 60 min; the optimized PSMS could be effectively separated in S‐8 macroporous resin coupled with C18. The relative content of PSMS was increased from 0.42% in PSMS to 92.53% after C18 purification; the antioxidant activity test revealed that pinobanksin could exert antioxidant ability by binding catalase (CAT) enzyme. Second, it was found that pinobanksin could effectively inhibit the proliferation of SH‐SY5Y cells, mainly by binding to BCL2‐associated X (BAX), B‐cell lymphoma‐2 (BCL‐2), and cyclin‐dependent Kinase 4/6 (CDK4/6) to produce more hydrogen bonds to inhibit their activities. This study confirms the medicinal potential of pinobanksin and provides the basis for the proper understanding of pinobanksin and the development of related products.
Analysis of double‐diffusive hydrothermal flow in a domestic stack: The effect of side walls patterns
Authors: Hamza Naseer H. , Abdulkadhim Ammar , Mohsen Ali M. , Abed Azher M.
Published: November 2023

Domestic stack is considered to investigate the double‐diffusive laminar natural convection. The working fluid is a gaseous mixture that has similar physical properties to carbon dioxide. Knowing the patterns of gaseous mixture distribution and determining the carbon deposit regions can help in carbon capture problems. The present study uses the finite element method to numerically examine the double ratio‐diffusive physical phenomena in a rectangular‐trapezoidal enclosure and to simulate the stack under a wide range of dimensionless parameters, such as buoyancy ratio , Lewis number , and Rayleigh number for different aspect ratios. Nine different cases of the geometrical ratio are selected to cover most possible design configurations. The results indicate that increasing the Lewis number leads to augmented solutal transport but reduces heat transfer. However, both heat and mass transfer are observed by increasing the buoyancy ratio. It is worth mentioning that increasing the ratio of upper side length to base length from to leads to a significant increase in mass transfer by 75% and heat transfer enhancement ratio by around 50%.
Lateral flow in bedrock dominates baseflow and flood flow in a catchment underlain with permeable sedimentary rock in the high‐relief Chichibu Mountains
Authors: Asano Yuko , Kawasaki Masatoshi , Takatoku Kae , Uchida Taro , Hiroki Sotaro
Published: November 2023

Determining the mechanisms of runoff generation is essential to land and water resource conservation, but lateral flow processes in high‐relief mountain areas remain unclear due to the difficulty to observe and measure these processes. This study demonstrates that lateral flow in bedrock dominates both high and low flows in a catchment underlain with permeable sedimentary bedrock in the high‐relief Chichibu Mountains. Through measurement of precipitation, discharge, soil, and stream temperatures and tracers (SiO2 and δ18O) in the first‐order stream Bakemonozawa (0.51 km2) and comparison of its water balance with the nested Kawamata catchment (93.58 km2) i, we showed that 831–1012 mm/year or 47%–53% of annual precipitation leaked from Bakemonozawa. The streamflow was discharged from an average depth of 2.3 m or deeper, which were deeper than the measured deepest soil near the gauge. Furthermore, stream temperature decreased significantly during a large summer storm, demonstrating that the relative contribution of the deep bedrock flowpath increased. Large isotopic variation in precipitation was dampened in the stream, suggesting that most baseflow and some higher flows arose from groundwater storage with a constant isotopic ratio due to dispersion and mixing. The discharge–SiO2 relationship suggested at least two groundwater sources, namely, shallow and deep bedrock groundwater, with different runoff responses. Discharge increased dramatically when the catchment became wet, coinciding with the deep bedrock groundwater contribution. Further research is needed to clarify the hydrological characteristics of bedrock.
Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium
Authors: Oze Isao , Ito Hidemi , Koyanagi Yuriko N. , Abe Sarah Krull , Rahman Md. Shafiur , Islam Md. Rashedul , Saito Eiko , Gupta Prakash C. , Sawada Norie , Tamakoshi Akiko , Shu Xiao‐Ou , Sakata Ritsu , Malekzadeh Reza , Tsuji Ichiro , Kim Jeongseon , Nagata Chisato , You San‐Lin , Park Sue K. , Yuan Jian‐Min , Shin Myung‐Hee , Kweon Sun‐Seog , Pednekar Mangesh S. , Tsugane Shoichiro , Kimura Takashi , Gao Yu‐Tang , Cai Hui , Pourshams Akram , Lu Yukai , Kanemura Seiki , Wada Keiko , Sugawara Yumi , Chen Chien‐Jen , Chen Yu , Shin Aesun , Wang Renwei , Ahn Yoon‐Ok , Shin Min‐Ho , Ahsan Habibul , Boffetta Paolo , Chia Kee Seng , Qiao You‐Lin , Rothman Nathaniel , Zheng Wei , Inoue Manami , Kang Daehee , Matsuo Keitaro
Published: November 2023

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population‐based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2); normal (18.5‐22.9 kg/m2); overweight (23‐24.9 kg/m2); and obese (25+ kg/m2). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02‐1.38] for males, HR 1.30 [1.14‐1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.
Total synthesis of cassane‐type diterpenoid pikrosalvin
Authors: Huang Rou‐Jie , Ong Tiow‐Gan , Chein Rong‐Jie
Published: November 2023

This paper presents the first successful total synthesis of pikrosalvin, a compound naturally derived from Salvia officinalis, grounded on the structural framework delineated by Brieskorn and Fuchs. Our synthetic approach was underpinned by a biomimetic strategy inspired by the Stork–Eschenmoser hypothesis for the biosynthesis of terpenes via polyene cyclization. Starting with commercially available vanillic acid and geraniol, we strategically assembled pikrosalvin's structural core, consisting of a decalin A/B ring, an aromatic C ring, and a butyrolactone D ring. Challenges related to protective groups and specific catalytic conditions were effectively addressed, resulting in high product yields. We further demonstrated the efficacy and broad applicability of a combined‐acid‐catalyzed polyene cyclization methodology in the context of complex natural product synthesis. This study sets the stage for future biological and pharmacological investigations of pikrosalvin.
The ongoing rewriting of the therapeutic contract in Metacognitive Interpersonal Therapy for narcissistic personality disorder: The case of Mark
Authors: Dimaggio Giancarlo , Valentino Virginia
Published: November 2023

In order to effectively treat individuals suffering from Narcissistic Personality Disorder (NPD), it is crucial to establish therapeutic goals and identify tasks to achieve them. However, this is a challenging process with NPD patients because they often struggle to find meaningful goals beyond the pursuit of status. Moreover, in order to change Furthermore, to promote change, they must confront painful emotions such as shame, guilt, or fear, which they habitually try to avoid. Additionally, they face difficulties in forming a positive perception of their therapists and cooperating towards mutually agreed‐upon goals and tasks. As a consequence, NPD patients ask for change but hardly engage themselves in the work necessary to achieve it. Therapists therefore need to pay the uttermost attention to drafting, negotiating and continuously updating a reasonable and realistic therapeutic contract. In this paper we describe the story of a man in his thirties with NPD who was ridden with depression, guilt, envy and anger and did not find ways to pursue the healthy and adaptive behaviors he would need to pursue in order to leave a richer social life. The therapist overcame ruptures in the therapeutic alliance and then involved the patient in a process where they set the steps to follow, making sure the patient was convinced they made sense. After a contract was reached progress became possible. Implications for the role of the therapeutic contract in NPD treatment are discussed.
Application of a Precision‐Dosing Model to a Real‐World Cohort of Patients on Infliximab Maintenance Therapy: Drug Usage and Cost Analysis
Authors: Nguyen Anke L. , Gibson Peter R. , Upton Richard N. , Mould Diane R. , Sparrow Miles P.
Published: November 2023

Precision‐dosing models forecast infliximab doses to achieve targeted trough concentrations in patients with inflammatory bowel disease (IBD). These models have shown to reduce nonresponse and improve patient outcomes. We compared infliximab doses determined by iDOSE precision dosing with standard dosing, and the associated drug costs, in patients with IBD. In this retrospective study, patients with IBD treated with infliximab every 8 weeks at 5 mg/kg were included. An infliximab dose was named dose X if 3 previous infliximab doses, laboratory values including trough infliximab concentrations, and the patient's weight were recorded. The actual dose X was compared to an iDOSE‐predicted dose X. Net drug use and costs were evaluated. A total of 174 patients—56% men; median age, 36 (interquartile range, 29‐47) years; 135 with Crohn disease; and 31 with ulcerative colitis—were included, with 417 dose X recordings. Median prior infliximab therapy was 2 (0‐4) years. Comparing actual dose X with predicted dose X, 52% and 32% of doses were subtherapeutic when aiming for trough concentrations of 5‐10 and 3‐7 μg/mL, respectively. Treatment costs increased by 102% and 29% for the 2 trough ranges, respectively. On multivariate regression analysis, subtherapeutic infliximab concentrations were associated with ulcerative colitis compared with Crohn disease (odds ratio, 9.81; 95% confidence interval, 1.28‐75.40; P = .028) and predose X infliximab trough concentration [odds ratio, 0.07; 95% confidence interval, 0.03‐0.15; P < .001]. Over half of maintenance infliximab drug doses were too low to achieve infliximab blood concentrations of 5 μg/mL or greater. While applying precision dosing may improve patient outcomes, drug costs could be considerably greater.
Decision‐making processes behind seeking regular cardiac checkups for individuals with Marfan syndrome: A grounded theory study
Authors: Haruyama Sayoko , Torishima Masako , Kawasaki Hidenori , Wada Takahito , Kosugi Shinji
Published: November 2023

Patients with Marfan syndrome (MFS) present with various symptoms, such as aortic aneurysm/dissection, tall stature, and lens deviation. Among them, acute aortic dissection is a complication that leads to sudden death. Some individuals with MFS are reluctant to see a cardiologist and discontinue regular checkups until they develop life‐threatening complications. We conducted a grounded theory study to investigate how individuals with MFS decided whether to adhere to healthcare recommendations, specifically to attend cardiology appointments. The study recruited individuals with a clinical or genetic diagnosis of MFS from a Japanese university hospital and individuals from a support group. Semi‐structured interviews were conducted with 28 consenting participants. In this study, we identified the decision‐making processes of individuals with MFS concerning their cardiology visits. We extracted “perception of the gap between their health status and medical recommendations” as the central category. This decision‐making process consisted of three parts: (A) the process by which an individual with MFS sees a cardiologist for the first time, (B) the process by which an individual with MFS keeps up with cardiology checkups, and (C) the process by which parents bring their children with MFS to the cardiologist. Individuals who learned of the possibility of MFS decided whether to adhere to medical recommendations depending on how they perceived the gap between their health status and the medical recommendations. In addition to medical information and treatment experience, adaptation to MFS, which changed through interactions with others, influenced the perception of the gap. This study suggests the role of genetic counseling and molecular genetic diagnosis as factors that may facilitate adaptation to MFS. The involvement of genetic counselors is important for helping individuals with MFS keep up with regular checkups while affirming their own experiences. These results provide insight into adherence to medical recommendations for individuals with MFS.
Made in Africa – How to make local agricultural machinery manufacturing thrive
Authors: Daum Thomas , Adegbola Ygué Patrice , Kamau Geoffrey , Kergna Alpha Oumar , Daudu Christogonus , Adebowale Wahab Akeem , Adegbola Carine , Bett Charles , Mulinge Wellington , Zossou Roch Cedrique , Nientao Abdoulaye , Kirui Oliver , Oluwole Fatunbi Abiodun
Published: November 2023

Manufacturing has the potential to drive economic growth, job creation and poverty reduction, but African manufacturers face challenges in competing with global markets. Agricultural machinery manufacturing may be one niche where African manufacturers can succeed. This paper examines the challenges and opportunities facing local agricultural manufacturers in Africa based on a survey of 386 manufacturers in four countries and qualitative methods. Results show that small, dedicated entrepreneurs have created vibrant local machinery markets. These manufacturers have several comparative advantages, in particular, the ability to develop machinery adapted to local agroecological conditions but face challenges related to financing, human resources, utilities, raw materials, production equipment and the regulatory environment. The paper offers recommendations on how to support local manufacturers to make “Made in Africa” the first choice for African farmers and agro‐food processors.
Integrative single‐cell transcriptome analysis provides new insights into post‐COVID‐19 pulmonary fibrosis and potential therapeutic targets
Authors: Kim Yumin , Kim Yeongmin , Lim Hyobin Julianne , Kim Dae‐Kyum , Park Ji‐Hwan , Oh Chang‐Myung
Published: November 2023

The global COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 virus has resulted in a significant number of patients experiencing persistent symptoms, including post‐COVID pulmonary fibrosis (PCPF). This study aimed to identify novel therapeutic targets for PCPF using single‐cell RNA‐sequencing data from lung tissues of COVID‐19 patients, idiopathic pulmonary fibrosis (IPF) patients, and a rat transforming growth factor beta‐1‐induced fibrosis model treated with antifibrotic drugs. Patients with COVID‐19 had lower alveolar macrophage counts than healthy controls, whereas patients with COVID‐19 and IPF presented with elevated monocyte‐derived macrophage counts. A comparative transcriptome analysis showed that macrophages play a crucial role in IPF and COVID‐19 development and progression, and fibrosis‐ and inflammation‐associated genes were upregulated in both conditions. Functional enrichment analysis revealed the upregulation of inflammation and proteolysis and the downregulation of ribosome biogenesis. Cholesterol efflux and glycolysis were augmented in both macrophage types. The study suggests that antifibrotic drugs may reverse critical lung fibrosis mediators in COVID‐19. The results help clarify the molecular mechanisms underlying pulmonary fibrosis in patients with severe COVID‐19 and IPF and highlight the potential efficacy of antifibrotic drugs in COVID‐19 therapy. Collectively, all these findings may have significant implications for the development of new treatment strategies for PCPF.
Integrative proteomics and metabolomics study reveal enhanced immune responses by COVID‐19 vaccine booster shot against Omicron SARS‐CoV‐2 infection
Authors: Wang Beili , Yang Wenjing , Tong Yexin , Sun Mingjun , Quan Sheng , Zhu Jing , Zhang Qianwen , Qin Zhaoyu , Ni Yanxia , Zhao Ying , Wang Kouqiong , Zhang Chunyan , Zhang Yichi , Wang Zhenxin , Song Zhenju , Liu Huafen , Fang Hao , Kong Ziqing , Ding Chen , Guo Wei
Published: November 2023

Since its outbreak in late 2021, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been widely reported to be able to evade neutralizing antibodies, becoming more transmissible while causing milder symptoms than previous SARS‐CoV‐2 strains. Understanding the underlying molecular changes of Omicron SARS‐CoV‐2 infection and corresponding host responses are important to the control of Omicron COVID‐19 pandemic. In this study, we report an integrative proteomics and metabolomics investigation of serum samples from 80 COVID‐19 patients infected with Omicron SARS‐CoV‐2, as well as 160 control serum samples from 80 healthy individuals and 80 patients who had flu‐like symptoms but were negative for SARS‐CoV‐2 infection. The multiomics results indicated that Omicron SARS‐CoV‐2 infection caused significant changes to host serum proteome and metabolome comparing to the healthy controls and patients who had flu‐like symptoms without COVID‐19. Protein and metabolite changes also pointed to liver dysfunctions and potential damage to other host organs by Omicron SARS‐CoV‐2 infection. The Omicron COVID‐19 patients could be roughly divided into two subgroups based on their proteome differences. Interestingly, the subgroup who mostly had received full vaccination with booster shot had fewer coughing symptom, changed sphingomyelin lipid metabolism, and stronger immune responses including higher numbers of lymphocytes, monocytes, neutrophils, and upregulated proteins related to CD4+ T cells, CD8+ effector memory T cells (Tem), and conventional dendritic cells, revealing beneficial effects of full COVID‐19 vaccination against Omicron SARS‐CoV‐2 infection through molecular changes.
Prognosis of programmed ventricular stimulation in adult patients with syncope of unexplained origin: A historical cohort
Authors: Finkler Bruno Schaaf , Sant'Anna Roberto , Pinos Javier , Zanotta Danilo Barros , Moreira Thiago Camargo , de Jesus Felipe Della Barba , Batista Pedro Dutra , da Rocha Helena Guedes , de Lima Barbara Adelmann , Saffi Marco Aurélio Lumertz , de Lima Gustavo Glotz , Kruse Marcelo , Leiria Tiago Luiz Luz
Published: November 2023

Background

Programmed ventricular stimulation (PVS) during electrophysiological study (EPS), is a globally accepted tool for risk stratification of sudden cardiac death (SCD) in some specific clinical situations. The aim of this study was to evaluate the prognosis of ventricular arrhythmia induction in a cohort of patients with syncope of undetermined origin (SUO).

Methods

This is a historical cohort study in a population of patients with SUO referred for EPS between the years 2008–2021. In this interval, 575 patients underwent the procedure.

Results

Patients with induced ventricular arrhythmias had a higher occurrence of structural heart disease (36.7% vs. 76.5%), ischemic heart disease (28.2 vs. 57.1%), heart failure (15.5% vs. 34.4%), and lower left ventricular ejection fraction (59.16% vs. 47.51%), when compared to the outcome with a negative study. PVS triggered ventricular arrhythmias in 98 patients, 62 monomorphic and 36 polymorphic. During a median follow‐up of 37.6 months, 100 deaths occurred. Only the induction of sustained ventricular arrhythmias showed a significant association with the primary outcome (all‐cause mortality) with a p value <.001. After the performance of EPS, 142 patients underwent cardioverter‐defibrillator (ICD) implantation. At study follow‐up, 30 patients had therapies by the device. Only the induction of sustained monomorphic ventricular arrhythmia showed statistically significant association with appropriate therapies by the device (p = .012).

Conclusion

In patients with SUO, the induction of sustained monomorphic ventricular arrhythmia after programmed ventricular pacing is related to a worse prognosis, with a higher incidence of mortality and appropriate therapies by the ICD.
Robust assessment of associations between weather and eastern wild turkey nest success
Authors: Boone Wesley W. , Moorman Christopher E. , Moscicki David J. , Collier Bret A. , Chamberlain Michael J. , Terando Adam J. , Pacifici Krishna
Published: November 2023

Temperature and precipitation have been identified as factors that potentially influence eastern wild turkey (Meleagris gallopavo silvestris) reproduction, but robust analyses testing the relationship between weather parameters and turkey nest success are lacking. Therefore, we assessed how weather influenced turkey daily nest survival using 8 years of data collected from 715 nests across the southeastern United States. We also conducted exploratory analyses investigating if weather conditions during or prior to nesting best predicted nest success. We then assessed the possible implications of climate change through 2041–2060 for future eastern wild turkey daily nest survival and nest success for variables determined significant in analyses. During incubation, positive anomalies of minimum daily temperature were associated with greater daily nest survival. Precipitation during nesting was not a good predictor of daily nest survival. Exploratory analyses unexpectedly indicated that weather conditions in January prior to incubation were more important to nest success than weather conditions during incubation. In January, negative anomalies of minimum temperature and greater average daily precipitation were associated with greater nest success. Projections of future nest success or daily nest survival based on these relationships with the predictive covariates, and informed by climate models, suggest that nest success may increase as January precipitation increases and that daily nest survival may increase as temperature during incubation increases. These positive associations could be offset by a negative association between nest success and the expected increases in January minimum average temperature. Additional research is needed to investigate causes of these relationships and assess the implications of climate change for eastern wild turkey poult survival.
Video‐Based Decision Aids Improve Sleep Surgery Decision‐Making: A Randomized Controlled Trial
Authors: Gulati Arushi , Abdulbaki Hasan , Callander Jacquelyn K. , Cai Yi , Chang Jolie L.
Published: November 2023

Objectives

Decisional conflict (DC) is high in obstructive sleep apnea (OSA) surgical candidates interested in positive airway pressure (PAP) alternatives. We evaluated the impact of pre‐consultation video decision aids on patient DC and decision readiness.

Methods

Prior to consultation for PAP alternatives, adult OSA patients were enrolled and completed a questionnaire querying DC (scored 0 [no conflict]–100 [high conflict]) and decision readiness. Those considering ≥3 treatment options were categorized as “high‐conflict.” Patients were randomized to either an intervention group with video review about PAP and surgical options prior to their visit or to a control group that received no video review. Audio recordings of clinic visits were analyzed for patient engagement.

Results

Twenty‐five participants (control: n = 12, intervention: n = 13) were found to have comparably high DC (mean score: 40.0). Both groups experienced post‐visit improvements in DC scores (post‐consult: 25.2, p = 0.003) which did not differ between the two groups (intervention: 20.5 ± 15.1 vs. control: 11.7 ± 12.1 points, p = 0.13). The intervention group showed significant improvement in decision‐making stage after the visit, with 72.7% “close to selecting an option” (p = 0.04) versus 41.7% in the control group. Use of videos was not associated with any differences in patient satisfaction, engagement, or decision to pursue surgery (all p > 0.05). High‐conflict patients (n = 5) who reviewed pre‐visit videos (intervention sub‐group) spoke fewer words during the visit (687 ± 139 vs. 1120 ± 389 words, p = 0.047) and had shorter visit times (18.7 ± 2.9 vs. 24.3 ± 3.1 min, p = 0.02) than high‐conflict control patients.

Conclusions

Patients have high levels of DC when considering PAP alternatives. Use of video decision aids prior to sleep surgery consultation may improve the treatment decision‐making process.

Level of Evidence

2 Laryngoscope, 134:2958–2963, 2024
Prognostic Significance of Regional Disease in Young Patients with Oral Cancer: A Comparative Study
Authors: Yosefof Eyal , Tsur Nir , Zavdy Ofir , Kurman Noga , Dudkiewicz Dean , Yehuda Moshe , Bachar Gideon , Shpitzer Thomas , Mizrachi Aviram , Tzelnick Sharon
Published: November 2023

Background

Regional metastases are considered the most important prognostic factor in OSCC patients. We aimed to investigate the impact of regional disease among different age groups with OSCC.

Methods

A retrospective comparison between patients 40 years old or younger, 41–69 years old, and 70 years or older treated for OSCC between 2000 and 2020 in a tertiary‐care center.

Results

279 patients were included. The mean age was 65 ± 17.7 and 133 were male (47.7%). Thirty‐six (12.9%) were 40 years old or younger, 101 (36.2%) were 41–69 years and 142 (50.9%) were 70 years or older. Five‐year overall survival and disease‐specific survival (DSS) were significantly better among patients younger than 40 compared to the mid‐age group and patients 70 years or older (76.7% vs. 69.4% vs.48.2%, Log‐rank p < 0.001, and 76.7% vs. 75.3% vs. 46.5%, Log‐rank p < 0.001, respectively). While an association between regional spread and overall survival and DSS was demonstrated among all age groups, the odds ratio (OR) for death of any cause and death of disease regarding cervical metastasis was much higher among patients younger than 40 compared with the 41–69 and 70+ age groups (death of any cause‐OR = 23, p‐value = 0.008, OR = 2.6, p‐value = 0.026, OR = 2.4, p‐value = 0.13, respectively. Death of disease‐OR = 23, p‐value = 0.008, OR = 2.3, p‐value = 0.082, OR = 4.1, p‐value = 0.001, respectively). In univariate  analysis, regional metastasis was associated with disease‐free survival only among patients younger than 40 (p‐value = 0.04).

Conclusions

Regional metastases correspond with worse prognosis in young patients compared to older patients. These patients may benefit from a comprehensive treatment approach with close post‐treatment follow‐up.

Level of Evidence

3 Laryngoscope, 134:2212–2220, 2024
Soil enrichment of potentially toxic elements in relation to land‐use types in an alpine meadow of the Qinghai–Tibet Plateau
Authors: Luo Caiyun , Zuo Chao , Pan Sichen , Chen Jingrui , Chao Le , Sun Jiachen , Zhao Liang
Published: November 2023

The Qinghai–Tibet Plateau, a fragile ecosystem with unique biodiversity, is particularly susceptible to soil contamination from increasing anthropogenic activities like grazing and farming. However, research exploring the relationship between these factors remains limited. Our study examines soil changes and potentially toxic elements (PTEs) after converting alpine meadows, providing insight into the impact of land‐use in this area. We found significant differences in the concentrations of PTEs (Cd, Cr, Hg, and Pb) among the three land‐use types. Soil from Oat Field (OF) had lower levels of Cd, Cr, Hg, and Pb compared with Fence Enclosure (FE) and Winter Grazing (WG), indicating a potential uptake/phytoextraction of these elements by oats. Different profiles of soil physiochemical properties were also detected, particularly in the OF soil, which showed significantly lower available potassium, microbial carbon, and microbial nitrogen but higher soil bulk density and total and available phosphorus. Additionally, significant stratification was observed in soil concentrations of most studied PTEs and nutrients in FE and WG, but not in OF. Specifically, lower levels of As, Cr, and most nutrients were found in the top layer (0–10 cm) compared with the bottom layer (20–30 cm). By comparison, Cd and Hg showed higher concentrations in the top layer in FE. These contrasting trends suggest potential differences in the mobility or bioavailability of these elements in the soil of the alpine meadow. Furthermore, significantly negative correlations were found between most soil nutrients, and the concentrations of As, Cr, and Pb, whereas significantly positive associations were observed for soil nutrients with Cd and Hg. However, such relationships predominantly existed in soils of WG and FE, but not OF. Collectively, our results suggest the potentially disrupted PTE accumulation and nutrient distribution by anthropogenic activities, particularly agricultural practices within the studied land‐use types, and warrant further evaluation of the associated ecotoxicological risks.