bluuebunny/crossref_metadata_2025 huggingface dataset:
Four‐dimensional imaging for cryo‐electron microscopy experiments using molecular simulations and manifold learning
Authors: Yoshidome Takashi
Published: December 2023

Elucidating protein conformational changes is essential because conformational changes are closely related to the functions of proteins. Cryo‐electron microscopy (cryo‐EM) experiment can be used to reconstruct protein conformational changes via a method that involves using the experimental data (two‐dimensional protein images). In this study, a reconstruction method, referred to as the “four‐dimensional imaging,” was proposed. In our four‐dimensional imaging technique, the protein conformational change was obtained using the two‐dimensional protein images (the three‐dimensional electron density maps used in previously proposed techniques were not used). The protein conformation for each two‐dimensional protein image was obtained using our original protocol with molecular dynamics simulations. Using a manifold‐learning technique and two‐dimensional protein images, the protein conformations were arranged according to the conformational change of the protein. By arranging the protein conformations according to the arrangement of the protein images, four‐dimensional imaging is constructed. A simulation for a cryo‐EM experiment demonstrated the validity of our four‐dimensional imaging technique.
The relationship between patterns of negative life experiences and clinical presentation in a psychiatric sample
Authors: Young Choi Ji
Published: December 2023

Background

Attempts have been made to classify the patterns of polytraumatization using a person‐centered approach. However, most studies have only focused on maltreatment and interpersonal trauma and have been unable to examine various clinical symptoms.

Objectives

This study aimed to explore patterns of negative life experiences, including maltreatment, lifetime trauma, and recent stressful life events, and compare diverse dimensions of the clinical manifestations among the subtypes in a clinical sample.

Method

We investigated childhood maltreatment, lifetime trauma, and recent stressful events using a self‐report method in 1410 psychiatric patients; we classified the patterns of lifelong negative life experiences using latent profile analysis (LPA). We used the rates of psychiatric diagnosis, the Beck Depression Inventory, the Impact of Event Scale‐Revised (IES‐R‐K), and the Multiphasic Minnesota Personality Inventory‐2‐Restructured Form to compare various symptom dimensions among the derived subtypes.

Results

LPA indicated a four‐class solution: mild, recent stress, maltreatment, and multiple adversity group. The multiple adversity group experiencing both lifetime trauma and recent stressful life events, in addition to maltreatment, including sexual abuse, had a high rate of severe mental illness and more symptom dimensions of thought and behavior problems. However, the rates of depressive disorders and emotional/internalizing symptoms were not more than those in the other two groups (recent stress and maltreatment groups) experiencing moderate levels of lifetime trauma. There was no significant difference between the recent stress and maltreatment groups for most symptom dimensions.

Conclusions

The findings indicate that distinct symptom profiles may be associated with the pattern of negative experiences, suggesting that negative experiences need multidimensional investigation in clinical settings.
Systematic review of spatial abilities and virtual reality: The role of interaction
Authors: Gittinger Micha , Wiesche David
Published: December 2023

Background

The importance of spatial abilities for individuals' success in science, technology, engineering, and mathematics (STEM) domains has been well established. Researchers have also emphasized the need to train engineering students in spatial ability. Although virtual reality (VR) offers prospects for training spatial abilities, research on the design of VR training environments remains incomplete.

Purpose

This review aimed to reveal the link between individuals' interactions in a VR environment and their spatial abilities and provide guidance for future research and the design of training settings. We also aimed to support students by aligning their interactions with individuals' spatial abilities or by using interactive VR to foster these abilities to create more equal opportunities in the field of engineering.

Method

A systematic review of existing literature was conducted to categorize and discuss recent findings.

Results

The study found that the reviewed literature (i) mainly considered mental rotation; (ii) showed advantages for high‐spatial‐ability learners and disadvantages for low‐spatial‐ability learners when they use interactive VR; (iii) indicated training possibilities, especially for low‐spatial‐ability learners, when they use interactive VR; and (iv) showed changes in not only interaction but also visualization parameters between experimental and control groups.

Conclusion

Interactive VR can be used to develop spatial abilities, particularly in low‐ability learners. However, it can also hinder these learners and favor high‐ability learners. Further research focusing on the interactive part of VR and the role of spatial ability is required to support design choices.
Research progress of triazole derivatives in the discovery of agricultural chemicals
Authors: Song Hongyi , Wang Sheng , Cai Qingfeng , Chen Jixiang
Published: December 2023

Triazole groups play an important role in the construction of agricultural bioactive molecules, often acting as linking units to organically graft different pharmacophore groups, so as to obtain efficient and broad‐spectrum pesticide molecules. After decades of development, triazole derivatives have made remarkable achievements in the discovery of pesticides, especially the discovery of fungicides. In addition, highly effective triazole insecticides, herbicides, and anti‐plant virus agents have also been found, and commercial triazole pesticides have occupied a large market share. At present, the study of triazole compounds has become one of the important fields in the development of new pesticides. We systematically reviewed the application of triazole derivatives in the discovery of new pesticides since 2010, summarized the antifungal, antibacterial, insecticidal, herbicidal, and anti‐plant virus activities of triazole derivatives, and discussed the structure–activity relationship and mechanism of action in order to provide inspiration and ideas for the discovery of new triazole agrochemicals.
Epichordal vertebral column formation in Xenopus laevis
Authors: Takahashi Yu , Wakabayashi Ryota , Kitajima Satoshi , Uchiyama Hideho
Published: December 2023

Although Xenopus Laevis is the most widely used model amphibian, skeletal development of its vertebral column has not been well illustrated so far. The mode of vertebral column development in anurans has been classified into two modes: perichordal and epichordal. Xenopus vertebral column formation is believed to follow the epichordal mode, but this aspect has been underemphasized, and illustrative examples are currently unavailable to the scientific community. This study documents the entire process of vertebral column formation in X. laevis, from the initial neural arch formation to the completion of metamorphosis. These images reveal that the neural arch arises from the dorsal lamina and lateral pedicle primordia, with no strict adherence to an anteroposterior sequence. Unlike other species, Xenopus centrum primordia exclusively form at the expanded ventral margins of neural arches, rather than from the cartilaginous layer surrounding the notochord. These paired centrum primordia then fuse at the ventral midline, dorsal to the notochord, and subsequently the notochord degenerates. This mode of centrum formation differs from the traditional epichordal mode, indicating that Xenopus might have lost the ability to form a cartilaginous layer around the notochord. Instead, the neural arch's ventral margin appears to have evolved to incorporate centrum precursor cells at its base, thereby forming a centrum‐like structure compensating for the absence of a true centrum. It is widely accepted that postsacral vertebrae lack centra, only possessing neural arches, and eventually fuse with the hypochord to form the urostyle. However, we have shown that the paired ventral ends of the postsacral vertebrae also fuse at the midline to form a centrum‐like structure. This process might extend to the trunk region during centrum formation. In addition to these findings, we offer evolutionary insights into the reasons why Xenopus retains centrum primordia at the base of neural arches.
Azvudine and nirmatrelvir–ritonavir in hospitalized patients with moderate‐to‐severe COVID‐19: Emulation of a randomized target trial
Authors: Zhou Yiling , Liu Yi , Jiang Li , Zhang Renqing , Zhang Huohuo , Shi Qingyang , Yang Zhirong , Mao Yi , Liu Sha , Yang Zhibo , Ding Jialin , Zhou Yongzhao , Ren Bi , He Liping , Zhao Xing , Li Weimin , Li Sheyu , Liu Dan
Published: December 2023

To examine the effectiveness of azvudine and nirmatrelvir–ritonavir in treating hospitalized patients with moderate‐to‐severe COVID‐19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate‐to‐severe COVID‐19 without contraindications for azvudine or nirmatrelvir–ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir–ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all‐cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent‐to‐treat analyses, azvudine reduced all‐cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12–0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24–0.92). Nirmatrelvir–ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17–1.05), and its composite with all‐cause death (HR: 0.38; 95% CI: 0.18–0.81). The study did not identify credible subgroup effects. The per–protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir–ritonavir improved the prognosis of hospitalized adults with moderate‐to‐severe COVID‐19
Meldrum's acid derivates are MepA efflux pump inhibitors: In vitro and in silico essays
Authors: Araújo Isaac Moura , Pereira Raimundo Luiz Silva , de Araújo Ana Carolina Justino , Gonçalves Sheila Alves , Tintino Saulo Relison , Oliveira‐Tintino Cícera Datiane de Morais , de Menezes Irwin Rose Alencar , Salamoni Renata , Begnini Iêda Maria , Rebelo Ricardo Andrade , Silva Luiz Everson da , Gurgel Ana Pavla Almeida Diniz , Coutinho Henrique Douglas M.
Published: December 2023

Efflux pumps are proteins capable of expelling antibiotics from bacterial cells, have emerged as a major mechanism of bacterial resistance. In the ongoing pursuit to overcome and reduce bacterial resistance, novel substances are being explored as potential efflux pump inhibitors. Meldrum's acid, a synthetic molecule widely studied for its role in synthesizing bioactive compounds, holds promise in this regard. Therefore, the objective of this study is to evaluate the antibacterial activity of three derivatives of Meldrum's acid and assess their ability to inhibit efflux mechanisms, employing both in silico and in vitro approaches. The antibacterial activity of the derivatives was assessed using a broth microdilution testing method. Surprisingly, the derivatives did not exhibit direct antibacterial activity on their own. However, they displayed a significant effect in enhancing the efficacy of antibiotics, suggesting a potential role in potentiating their effects. Furthermore, fluorescence emission assays using ethidium bromide indicated that the derivatives could potentially block efflux pumps, as they exhibited fluorescence levels comparable to the positive control. To further investigate their inhibitory capacity, molecular docking studies were conducted in silico, revealing binding interactions similar to ciprofloxacin and carbonyl cyanide 3‐chlorophenylhydrazone, known efflux pump inhibitors. These findings highlight the potential of Meldrum's acid derivatives as effective inhibitors of efflux pumps. By targeting these mechanisms, the derivatives offer a promising avenue to enhance the effectiveness of antibiotics and combat bacterial resistance. This study underscores the importance of exploring novel strategies in the fight against bacterial resistance and provides valuable insights into the potential of Meldrum's acid derivatives as efflux pump inhibitors. Further research and exploration in this field are warranted to fully exploit their therapeutic potential.
Evaluating the impact of the Storegga tsunami on Mesolithic communities in Northumberland
Authors: Sharrocks Patrick D , Hill Jon
Published: December 2023

The Holocene Storegga tsunami, 8120–8175 cal a bp, resulted in run‐up heights of up to 3–6 m around mainland UK and coincided with a suggested large population decline in the coastally focused Mesolithic population in Northern Britain. At Howick, Northumberland, the site of a Mesolithic settlement, a nearby sediment deposit may be of tsunamigenic origin, but this is uncertain. Here, a numerical model was used to simulate the Storegga tsunami in Northumberland. Two scenarios of relative sea‐level change, and a third incorporating high tide, were simulated with mortality estimated within the intertidal zone for the Mesolithic sites in the region. The results showed that only with the addition of high tide could the sediment deposit site have been inundated by the tsunami. At Howick, mortality estimates varied but were up to 100% within the resource‐rich intertidal zone. The tsunami inundated a large area and would have led to the loss of key resources such as hazelnuts prior to the winter months. These combined effects would have probably been replicated throughout coastal settlements in Northern Britain, possibly leading to the contemporary population decline estimated to have occurred at this time.
Colon‐Targeted Oral Delivery of Hydroxyethyl Starch–Curcumin Microcapsules Loaded with Multiple Drugs Alleviates DSS‐Induced Ulcerative Colitis in Mice
Authors: Huang Da , Zou Minglang , Xu Chenlan , Wang Yongming , Xu Zhenjin , Zhang Wancong , Tang Shijie , Weng Zuquan
Published: December 2023

Combination therapy through colon‐targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch–curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug‐loaded microcapsules (CS/DA‐loaded HES─CUR microcapsules, CDHC‐MCs) tailored for colon‐targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC‐MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran‐sulfate‐sodium‐induced UC mouse model reveal that CDHC‐MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation‐related splenomegaly. These findings highlight the potential of colon‐targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC‐MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.
NLRP3/IL‐1β induced myeloid‐derived suppressor cells recruitment and PD‐L1 upregulation promotes oxaliplatin resistance of hepatocellular carcinoma
Authors: Liu Wenfeng , Zhang Feng , Quan Bing , Yao Fan , Chen Rongxin , Ren Zhenggang , Yin Xin
Published: December 2023

Oxaliplatin is commonly used as the first‐line chemotherapeutic agent for advanced hepatocellular carcinoma (HCC). Unfortunately, the acquired resistance, limits the effectiveness of oxaliplatin and the underlying mechanisms remain unknown. Therefore, we explored the role of NOD‐like receptor protein 3 (NLRP3)/IL‐1β in mediating oxaliplatin resistance in HCC. We observed that NLRP3/IL‐1β expression was much higher in oxaliplatin‐resistant HCC cells. To further understand its impact on drug resistance, we knocked down NLRP3 and observed that it sensitized HCC cells to the growth‐inhibitory effects of oxaliplatin and induced cell apoptosis. NLRP3/IL‐1β overexpressing tumor cells also attracted polymorphonuclear myeloid‐derived suppressor cells. Using mouse models, we demonstrated that NLRP3/IL‐1β inhibition by short hairpin RNA or MCC950 effectively overcame oxaliplatin resistance. Furthermore, NLRP3/IL‐1β inhibition resulted in reduced expression of PD‐L1. We also found that PD‐L1 antibody combined with NLRP3/IL‐1β blockade displayed significant antitumor effect in HCC. Overall, our study provides compelling evidence supporting the essential role of NLRP3/IL‐1β in conferring resistance to oxaliplatin and reshaping the immunosuppressive microenvironment in HCC. Targeting NLRP3/IL‐1β presents a potential therapeutic target for overcoming oxaliplatin resistance and reshaping microenvironment of HCC.
A novel approach to calculate weighted average cost of capital (WACC) considering debt and firm's cash flow durations
Authors: Rodríguez Rafael A.
Published: December 2023

This paper presents a novel approach to calculate the weighted average cost of capital (WACC) but considering additional relevant variables to be applied to a specific cash flow, free cash flow to firm (FCFF), or capital cash flow (CCF), in order to value an asset. The analytical expressions deduced for this approach, one for each case, are based not only on the ratio debt to the value of the asset and the cost of debt and equity, as in the usual expression, but also includes the debt and firm's cash flow durations. The proposed novel approach to cost of capital has key advantages in comparison to the usual expression for WACC:

It is an analytical expression that could be applied to whatever kind of debt or capital structure, not only perpetual debt or permanent capital structure.

It is a single discount rate, and for its calculation, it is not necessary to recalculate financial factors involved, which makes easier its application.

The additional financial variables involved, debt and firm's cash flow duration, allow to obtain better results for the right discount rate and for the value of an asset in the sense that the discount rate for the asset effectively will permit to reach the required level for the profitability for the investor and to cover the cost of debt.
Variation in resource competition traits among Microcystis strains is affected by their microbiomes
Authors: Baker Dylan , Godwin Casey M. , Khanam Muhtamim , Burtner Ashley M. , Dick Gregory J. , Denef Vincent J.
Published: December 2023

Freshwater harmful algal blooms are often dominated by Microcystis, a phylogenetically cohesive group of cyanobacteria marked by extensive genetic and physiological diversity. We have previously shown that this genetic diversity and the presence of a microbiome of heterotrophic bacteria influences competitive interactions with eukaryotic phytoplankton. In this study, we sought to explain these observations by characterizing Monod equation parameters for resource usage (maximum growth rate μmax, half‐saturation value for growth Ks, and quota) as a function of N and P levels for four strains (NIES‐843, PCC 9701, PCC 7806 [WT], and PCC 7806 ΔmcyB) in presence and absence of a microbiome derived from Microcystis isolated from Lake Erie. Results indicated limited differences in maximum growth rates but more pronounced differences in half‐saturation values among Microcystis strains. The largest impact of the microbiome was reducing the minimal nitrogen concentration sustaining growth and reducing half saturation values, with variable results depending on the Microcystis strain. Microcystis strains also differed from each other in their N and P quotas and the extent to which microbiome presence affected them. Our data highlight the importance of the microbiome in altering Microcystis‐intrinsic traits, strain competitive hierarchies, and thus bloom dynamics. As quota, μmax, and Ks are commonly used in models for harmful algal blooms, our data suggest that model improvement may be possible by incorporating genotype dependencies of resource‐use parameters.
Initial validation of the Mass. General Neuropathy Exam Tool (MAGNET) for evaluation of distal small‐fiber neuropathy
Authors: Zirpoli Gary R. , Farhad Khosro , Klein Madeleine C. , Downs Sean , Klein Max M. , Oaklander Anne Louise
Published: December 2023

Introduction/Aims

Diagnosis of small‐fiber neuropathy (SFN) is hampered by its subjective symptoms and signs. Confirmatory testing is insufficiently available and expensive, so predictive examinations have value. However, few support the 2020 SFN consensus‐case‐definition requirements or were validated for non‐diabetes neuropathies. Thus we developed the Massachusetts General Hospital Neuropathy Exam Tool (MAGNET) and measured diagnostic performance in 160 symptomatic patients evaluated for length‐dependent SFN from any cause and 37 healthy volunteers.

Methods

We compared prevalences of abnormalities (vital signs, pupil responses, lower‐limb appearance, pin, light touch, vibration and position sensitivity, great‐toe strength, muscle stretch reflexes), and validated diagnostic performance against objective SFN tests: lower‐leg skin‐biopsy epidermal neurite densities and autonomic function testing (AFT). Sensitivity/specificity, feasibility, test–retest and inter‐rater reliability, and convergence with the Utah Early Neuropathy Scale were calculated.

Results

Patients’ ages averaged 48.5 ± 14.7 years and 70.6% were female. Causes of neuropathy varied, remaining unknown in 59.5%. Among the 46 with abnormal skin biopsies, the most prevalent abnormality was reduced pin sharpness at the toes (71.7%). Inter‐rater reliability, test–retest reliability, and convergent validity excelled (range = 91.3–95.6%). Receiver operating characteristics comparing all symptomatic patients versus healthy controls indicated that a MAGNET threshold score of 14 maximized predictive accuracy for skin biopsies (0.74) and a 30 cut‐off maximized accuracy for predicting AFT (0.60). Analyzing patients with any abnormal neuropathy‐test results identified areas‐under‐the‐curves of 0.87–0.89 for predicting a diagnostic result, accuracy = 0.80–0.89, and Youden's index = 0.62. Overall, MAGNET was 80%–85% accurate for stratifying patients with abnormal versus normal neuropathy test results.

Discussion

MAGNET quickly generates research‐quality metrics during clinical examinations.
Bioequivalence study followed by model‐informed dose optimization of a powder for oral suspension of 6‐mercaptopurine
Authors: Arun Bhavatharini , Joshi Mahendra , Kakkar Archana Khosa , Madki Shivkumar , Ivaturi Vijay , Chinnaswamy Girish , Banavali Shripad , Gota Vikram
Published: December 2023

Background

6‐Mercaptopurine (6MP) is the mainstay chemotherapy for acute lymphoblastic leukemia (ALL) and is conventionally available as 50 mg tablets. A new 6MP powder for oral suspension (PFOS 10 mg/mL) was developed recently by IDRS Labs, India, intended for pediatric use. A comparative pharmacokinetics of PFOS with T. mercaptopurine was conducted to determine the dose equivalence.

Methods

An open‐label, randomized, two‐treatment, two‐period, two‐sequence, single oral dose, crossover, bioequivalence study was conducted on 51 healthy adult subjects. Post hoc, a population pharmacokinetic (PopPK) model was developed using the healthy volunteer data to perform simulations with various PFOS doses and select a bioequivalent dose. Further, to confirm the safety of PFOS in pediatrics, a simulation of 6MP and 6‐thioguanine exposures was performed by incorporating the formulation‐specific parameters derived from the healthy volunteer study into the PopPK model in childhood ALL available in literature.

Results

The 6MP PFOS had 47% higher oral bioavailability compared to the reference product. Simulations using a two‐compartmental PopPK model with dissolution and transit compartments showed that 40 mg of PFOS was found to be equivalent to 50 mg tablets. The simulated 6‐thioguanine nucleotide concentrations in children using the dose adjusted for PFOS were between 114 and 703.6 pmol/8 × 108 RBC, which was within the range reported in pediatric ALL studies.

Conclusion

6MP PFOS 10 mg/mL should be administered at a 20% lower dose than the tablet to achieve comparable exposure. 6MP PFOS addresses an unmet medical need for a liquid formulation of 6MP in the Indian subcontinent.
A nursing perspective on inpatient sleep and circadian disruptions for pediatric stem cell transplant patients
Authors: Zhou Eric S. , Revette Anna , Waitt Julie , Lehmann Leslie E. , Diller Lisa R. , Emmons Karen M. , Valenzuela Ariana F. , Redline Susan
Published: December 2023

Background

Children treated with stem cell transplant (SCT) are routinely hospitalized for long periods where they are exposed to significant sleep and circadian disruptions. As nurses play a primary role in symptom management during SCT, we sought to understand their perspective on patient sleep and circadian disruptions, perceived barriers to a good sleep and circadian environment, and suggestions for improvement.

Procedure

Four focus groups were conducted with pediatric SCT nurses (N = 25 participants). A semistructured focus group guide was administered, with the discussions recorded and transcribed. A multistage thematic analysis combining prefigured and emergent dimensions was conducted. Our analysis focused on drawing comparisons within and across focus groups to understand the unique work experiences that participants had related to the patient's sleep and circadian environment.

Results

Three key themes emerged. First, nurses expressed a high awareness of how disruptive the hospital environment is for patients. Second, nurses described their extensive efforts to try to minimize the impact of these disruptions. Finally, they provided clear recommendations for how to improve upon these concerns, along with barriers that they perceive could impede implementation.

Conclusions

Front‐line caregivers on a pediatric SCT unit describe key contributors to sleep/circadian disturbances for patients. Within the constraints of the considerable medical needs of this patient population and the physical room/hospital environment, nurses strive to minimize these disruptions to the best of their ability. It is crucial that hospitals assess and remediate these disturbances for these children that have important implications for overall health.
Remote hands‐on training with a novel “video‐game” simulator for teaching fetoscopic laser techniques for ablation of placental anastomoses in twin‐to‐twin syndrome
Authors: Windrim Catherine , Ryan Greg , Rojas David , Montero Daniel , Higgins Mary , Windrim Rory
Published: December 2023

Key points

What's already known about this topic?

Twin to twin syndrome (TTTS) is a serious complication of monochorionic twin pregnancy

The treatment of choice is fetoscopic laser ablation of placental anastamoses

Simulation plays an important role in teaching this high‐acuity procedure

What does this study add?

We report the development of a high‐fidelity digital simulation system for teaching TTTS fetoscopic lasers

Remote teaching has been demonstrated to work well with this system

This simulator is robust, easy to store and assemble and relatively inexpensive.
A novel NONO nonsense variant in a fetus with renal abnormalities
Authors: Rodriguez‐Revenga Laia , Nadal Alfons , Borobio Virginia , Álvarez‐Mora Maria Isabel , Madrigal Irene , Pauta Montse , Borrell Antoni
Published: December 2023

At 16 + 6‐weeks a fetal scan performed in the second pregnancy of a 42 y.o. woman identified a right multicystic dysplastic kidney, left renal agenesis, absent urinary bladder, myocardial hypertrophy, increased nuchal fold, a single umbilical artery, and oligohydramnios. Trio exome sequencing analysis detected a novel pathogenic NONO variant. Postmortem examination after the termination of pregnancy confirmed the ultrasound findings and also revealed pulmonary hypoplasia, retrognathia and low‐set ears. The variant was a novel de novo hemizygous pathogenic loss‐of‐function variant in NONO [NM_007363.5], associated with a rare X‐linked recessive neurodevelopmental disorder, named intellectual developmental disorder, X‐linked syndromic 34 (OMIM#300967). The postnatal characteristic features of this disorder include intellectual disability, developmental delay, macrocephaly, structural abnormalities involving the corpus callosum and/or cerebellum, left ventricular noncompaction and other congenital heart defects. In the prenatal setting, the phenotype has been poorly described, with all described cases presenting with heart defects. This case highlights the need of further clinical delineation to include renal abnormalities in the prenatal phenotype spectrum.
Antifungal medication use during pregnancy and the risk of selected major birth defects in the National Birth Defects Prevention Study, 1997–2011
Authors: Papadopoulos Eleni A. , Howley Meredith M. , Fisher Sarah C. , Van Zutphen Alissa R. , Werler Martha M. , Romitti Paul A. , Browne Marilyn L. ,   for the National Birth Defects Prevention Study
Published: December 2023

Purpose

Recent studies suggest increased birth defect risk associated with maternal use of specific oral antifungals. We estimated associations between first‐trimester antifungal use and selected non‐cardiac birth defects using National Birth Defects Prevention Study (NBDPS) data.

Methods

Participants with a pregnancy affected by a study‐eligible birth defect (“cases”) were ascertained from 10 birth defect surveillance programs; participants who delivered livebirths without a major birth defect (“controls”) were randomly selected from birth records or hospital discharge lists. First‐trimester antifungal use was self‐reported via maternal interview. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects with ≥5 exposed cases using logistic regression. We estimated crude ORs and exact 95% CIs for birth defects with 3–4 exposed cases. Additionally, we conducted a probabilistic bias analysis of exposure misclassification.

Results

Our analysis included 19 624 cases and 11 427 controls; 257 (1.3%) cases and 123 (1.1%) controls reported first‐trimester antifungal use. Of those who reported antifungals, 62.6% of cases and 64.2% of controls reported topical antifungals; 10.1% of cases and 4.9% of controls reported oral antifungals. We observed the strongest associations for encephalocele and Dandy‐Walker malformation and modestly elevated estimates for several other defects. Bias‐adjusted estimates were similar to the main analysis.

Conclusion

First‐trimester antifungal use was positively associated with several birth defects in our analysis, although CIs were imprecise. Further study is warranted to investigate associations between antifungal use and birth defects, including potential bias due to confounding by indication.
To retrieve values of albuminuria to define the size of CKD patients eligible to SGLT‐2Is: An explorative analysis using a primary care database
Authors: Lapi Francesco , Marconi Ettore , Piccinocchi Gaetano , Medea Gerardo , Piccinni Carlo , Maggioni Aldo Pietro , Cricelli Claudio
Published: December 2023

Purpose

To address missingness of albuminuria values, which establish the eligibility to SGLT‐2Is for patients with CKD, using the multiple imputation (MI) method.

Methods

We selected patients aged 18 or older and diagnosed with CKD in a primary care database. Those with severe CKD and/or previously treated with SGLT‐2Is were excluded. Then, we collected all available information on albuminuria within 90 days the measure of GFR. A value of albumin‐creatinine ratio (ACR) ranging 200–5000 mg/g or otherwise was the response variable on which we ran MI. Using logistic regression, odds ratios (OR) and related 95% confidence intervals (CI) were estimated for each covariate toward the response variable for both full and imputed dataset.

Results

The determinants showed consistent estimates between the full and imputed datasets as demonstrated by the overlaps of the CIs and the similar point estimates. As expected, there were some exceptions, such as diabetes (OR of 1.2 vs. 0.5) and use of diabetic medications (OR of 1.0 vs. 2.1) and/or statins (OR of 1.1 vs. 1.8).

Conclusions

Besides being a reminder for GPs to prescribe and register albuminuria in certain patients' categories, these determinants might be translated into an operational algorithm to input ACR values in administrative data sources. Scenarios for the reimbursement criteria regulating SGLT‐2Is to treat CKD would be therefore simulated on more inferable estimates.
Austrian farmers perception of new weeds
Authors: Glaser Michael , Essl Franz , Follak Swen
Published: December 2023

The composition of weed floras in Central European fields has shifted creating a novel management issue: new weeds, that is, species that are currently spreading and increasing in impact. In their role as primary decision makers on the ground, farmers' perception of these new weeds plays a pivotal role in collecting information on their occurrence and control. We conducted an online survey to determine if Austrian farmers recognized 15 selected new weed taxa (12 species and 3 genera) from their farm. The 181 surveyed farmers also estimated the required management effort for these species and elicited their current management practices. Additional questions were posed to understand farmers' general perception of changes in the weed flora. We used a generalized linear mixed model to estimate differences in management effort and identify new weeds that merit monitoring and management programs. Two weed genera (Fallopia spp. and Panicum spp.) showed significantly higher than average management effort. The most commonly used management measures were manual removal, herbicide use and crop rotation. A majority of farmers reported changes in the weed flora; over two thirds reported new species and over one third reported new weeds that were difficult to control. In summary, our results suggest that respondents were aware of the challenges posed by new weeds but required more information on management and prevention strategies.
Long term update on toxicity and survival of a phase II trial of linac‐based stereotactic body radiation therapy for low‐intermediate risk prostate cancer
Authors: D'Agostino Giuseppe R. , Badalamenti Marco , Stefanini Sara , Baldaccini Davide , Franzese Ciro , Faro Lorenzo Lo , Di Cristina Luciana , Vernier Veronica , Reggiori Giacomo , Scorsetti Marta
Published: December 2023

Background

In 2016 we published a phase II study exploring safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) delivered with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams techniques in prostate cancer (PC) patients. We present herein the updated results on late toxicity and long‐term survival.

Methods

Patients enrolled in the study had a biopsy‐confirmed localized PC and the features of a low‐ or intermediate‐risk disease (National Comprehensive Network Criteria). The radiotherapy (RT) schedule consisted of 35 Gy delivered in five fractions every other day. Toxicities were registered according to the common toxicity adverse events v4.0. Biochemical recurrence was defined as an increase of prostate specific antigen after nadir, confirmed at least once. Local recurrence (LR) and distant metastases were detected either with Choline‐ or PSMA‐PET/CT scans.

Kaplan‐Meier curves for Biochemical Recurrence‐Free Survival (BFS), Local Control (LC), Distant Metastasis Free Survival (DMFS) and Cancer Specific Survival, were calculated by using MedCalc.

Results

Ninety patients were submitted to SBRT between February 2012 and March 2015. Fifty‐eight patients (64.5%) had a Gleason Score of 6, while 32 (35.5%) had a Gleason Score of 7. A late grade 1 Genito‐Urinary toxicity was observed in 54.5% of patients while a grade 2 in 3.3%. A late Gastro‐intestinal grade 1 toxicity was reported in 18.9% of patients, while a grade 2 in 2.2%. Erectile dysfunction was reported by 13% of patients No heavier toxicities were observed. At a median follow‐up of 102 months, 5‐ and 8‐year BFS were 93.0% and 84.4% respectively, 5‐ and 8‐year LC were 95.2% and 87.0% respectively, 5‐ and 8‐year DMFS were 95.3% and 88.4%, respectively.

Conclusions

This long‐term update confirms that SBRT is a valid therapeutic strategy for low‐intermediate risk PC. RT with VMAT and FFF warrants optimal results in terms of toxicity and disease control.
Prescribed performance‐based resilient model‐free adaptive control for CPSs against aperiodic DoS attacks
Authors: Sun Shan‐Shan , Li Yuan‐Xin , Hou Zhongsheng
Published: December 2023

This paper presents a prescribed performance‐based model‐free adaptive resilient control (MFARC) algorithm to address the realization of trajectory tracking for nonlinear cyber‐physical systems (CPSs) under aperiodic denial‐of‐service (DoS) attacks. Firstly, an equivalent linear model is constructed by utilizing the dynamic linearization technique, and a novel output transformation approach is applied to convert the constrained system to an unconstrained one for the MFARC framework. Then, an attack compensation mechanism is presented to estimate the unavailable output signal when attacks are active, such that the negative impact of aperiodic DoS attacks can be compensated. Based on the unconstrained model and the compensation mechanism, a prescribed performance‐based MFARC strategy is constructed to steer the tracking error to the predetermined neighborhood around the origin in the presence of DoS attacks. A major improvement of our result over previous studies is the introduction of prescribed performance control (PPC) into MFARC while reasonably restricting the transient and steady‐state performance of the tracking error even when DoS attacks occur. Additionally, we utilize the linear matrix inequality (LMI) toolbox to obtain better tracking performance by suitably adjusting the time‐varying parameters, which is superior in practical applications. Ultimately, our results indicate that the tracking error consistently remains within a predefined bound.
Bayesian inference for prediction of survival probability in prime‐boost vaccination regimes
Authors: Lu Yuelin , Carlin Bradley P. , Seaman John W.
Published: December 2023

We focus on Bayesian inference for survival probabilities in a prime‐boost vaccination regime in the development of an Ebola vaccine. We are interested in the heterologous prime‐boost regimen (unmatched vaccine deliverys using the same antigen) due to its demonstrated durable immunity, well‐tolerated safety profile, and suitability as a population vaccination strategy. Our research is motivated by the need to estimate the survival probability given the administered dosage. To do so, we establish two key relationships. Firstly, we model the connection between the designed dose concentration and the induced antibody count using a Bayesian response surface model. Secondly, we model the association between the antibody count and the probability of survival when experimental subjects are exposed to the Ebola virus in a controlled setting using a Bayesian probability of survival model. Finally, we employ a combination of the two models with dose concentration as the predictor of the survival probability for a future vaccinated population. We implement our two‐level Bayesian model in Stan, and illustrate its use with simulated and real‐world data. Performance of this model is evaluated via simulation. Our work offers a new application of drug synergy models to examine prime‐boost vaccine efficacy, and does so using a hierarchical Bayesian framework that allows us to use dose concentration to predict survival probability.
How do veterinary students perceive and prepare for compulsory slaughterhouse visits?
Authors: Wigham Eleanor E. , Yusta Noelia , Sweet Sydney M. , Francesca Lauren , Dadios Nikolaos , Nova Rodrigo J.
Published: December 2023

Background

Veterinary students in the UK must visit a slaughterhouse as part of their studies. There is currently limited evidence exploring how students perceive these visits or which activities have been implemented to support learning during a visit that may be emotionally challenging.

Methods

Veterinary students at the Royal Veterinary College and the University of Glasgow were invited to complete an online survey and participate in follow‐up focus groups.

Results

Participants appreciated the important role that veterinarians play in the slaughterhouse. Most (69%) agreed that in‐person visits are important and would choose to visit, with around half (49%) thinking it should be optional. Previous slaughterhouse experience improved students’ views towards compulsory in‐person visits. Teaching events covering the slaughter process, videos and discussion sessions were perceived as useful preparatory activities. Anxiety was the most common emotion associated with visits.

Limitations

The response rate was low, at 15.6%, and a small number of students participated in focus groups. Data on diets and gender were not collected.

Conclusion

Slaughterhouse visits are valued by students, although they can cause negative emotions. Managing expectations and increasing awareness of visitation requirements during the application process and subsequent studies may improve the educational and emotional experience of visits.
The effects of climate change on the natural rate of interest: A critical survey
Authors: Mongelli Francesco Paolo , Pointner Wolfgang , van den End Jan Willem
Published: December 2023

This survey reviews the literature about the possible impacts of climate change on the natural rate of interest (r*), an important yardstick for monetary policy. Prima facie, economic, and financial developments can lower r* in scenarios with increasing climate‐related damages and uncertainty that reduce productivity growth and raise precautionary savings. Orderly climate policies have a pivotal role in facilitating the transition to a carbon‐neutral economy and supporting a steady investment flow. We discuss the main models used to simulate the effects of climate change on r* and summarize the outcomes. However, in scenarios that assume innovations and investments induced by transition policies, r* could be affected positively. Overall, the downward effects of climate change on r* can be substantial, even considering the high degree of uncertainty about the outcomes, with tipping points and nonlinear effects aggravating the economic impacts. The downward pressure on r* will further challenge monetary policy in the long run, by limiting its policy space.

This article is categorized under:

Climate Economics > Economics and Climate Change

Assessing Impacts of Climate Change > Evaluating Future Impacts of Climate Change
Talking with Spies: From Naïve to Distrustful Researcher
Authors: Díaz-Fernández Antonio M.
Published: December 2023

Intelligence officers – generally known as ‘spies’ – will not openly admit, even within their own family circles, that they work for an intelligence service. These agencies have neither local offices nor facilities, nor do they visit schools to talk about the daily life and work of their officers. Public media appearances are extremely rare, and it is usually only the director of the agency whose face is seen in public. Innate secretiveness and the inaccessibility of many official archives are obstacles to transparent research on intelligence services. In 1998, I commenced my doctoral thesis on the Spanish intelligence services. Far from being a passing adventure, the topic became my principal line of research for over two decades, during which time I completed almost 250 interviews, including 100 with members and ex-members of the intelligence services and another 50 with heads of government, Spanish and foreign intelligence service directors, military staff, politicians, and diplomats. In this chapter, I present my fieldwork experience of interviewing intelligence officers and the evolution of a young and somewhat naïve researcher into a more mature and distrustful one.
Researching the Roma in Criminology and Legal Studies: Experiences from Urban and Rural Participant Observation, Interviews, and Surveys
Authors: Molnar Lorena , Vallés Marc H.
Published: December 2023

The Roma are the largest European minority and among the groups that have suffered the most dreadful persecution and trauma in the past that persists today. This chapter addresses the fieldwork experiences of two early career researchers who conducted criminological and socio-legal studies on several Roma groups in urban and rural settings in two countries. We discuss the particularities necessary to access the field and gain the participants’ acceptance, those both with and without Roma ethnicity, through diverse gatekeepers, i.e., a network of acquaintances, as well as NGOs. We used such data collection methods as interviews and self-reported surveys in our studies, the procedures and challenges of which are discussed herein. Emotional and ethical challenges in our studies were related to the dilemmas with respect to our role as researchers and witnesses of poverty and difficult situations or testimonies. We argue that the adaptation of tools, integration of researchers who share an ethnic or linguistic background with the participants, thorough reflection on the researchers’ role, and an open-minded attitude that accepts the participants’ cosmovision are necessary to conduct fruitful research among the Roma.
Doing Research on, for and with Police in Canada and Switzerland: Practical and Methodological Insights
Authors: Burkhardt Christine , Boivin Rémi
Published: December 2023

This chapter focuses on policing research, distinguishing among research conducted on, for or with the police and addresses various stages of the research process considered sensitive or crucial. For researchers, police organisations are fascinating subjects, albeit challenging to access and sometimes reluctant to scientific input. From access to the fieldwork and dissemination of findings, several challenges can arise, including those that are administrative, methodological, ethical or emotional. Anecdotes, guidelines and avenues for reflection are formulated to guide researchers in conducting applied research in policing. Although policing is a rich source for criminological studies, police science and applied research remain underexploited. Police and academia need to understand and accept each other’s competencies, resources and contributions.
Conclusions: Deciphering the Unspoken: A Collective Examination of Sensitive Fieldwork Experiences in Criminology and Security Studies
Authors: Díaz-Fernández Antonio M. , Del-Real Cristina , Molnar Lorena
Published: December 2023

Preceding these conclusions are the experiences of 55 researchers from 40 Universities and research centers across four continents. These scholars have accumulated a collective experience of over 700 years in fieldwork, starting as early as the 1980s. Rather than a mere compilation of authors’ experiences, we aimed to undertake a comprehensive analysis of their research endeavors, extracting valuable lessons to enhance criminology and security studies in sensitive areas. The extensive review of chapters revealed both commonalities and unique aspects among the research projects.