bluuebunny/crossref_metadata_2025 huggingface dataset:
The pupil dilation response as an indicator of visual cue uncertainty and auditory outcome surprise
Authors: Becker Janika , Viertler Marvin , Korn Christoph W. , Blank Helen
Published: March 2024

In everyday perception, we combine incoming sensory information with prior expectations. Expectations can be induced by cues that indicate the probability of following sensory events. The information provided by cues may differ and hence lead to different levels of uncertainty about which event will follow. In this experiment, we employed pupillometry to investigate whether the pupil dilation response to visual cues varies depending on the level of cue‐associated uncertainty about a following auditory outcome. Also, we tested whether the pupil dilation response reflects the amount of surprise about the subsequently presented auditory stimulus. In each trial, participants were presented with a visual cue (face image) which was followed by an auditory outcome (spoken vowel). After the face cue, participants had to indicate by keypress which of three auditory vowels they expected to hear next. We manipulated the cue‐associated uncertainty by varying the probabilistic cue‐outcome contingencies: One face was most likely followed by one specific vowel (low cue uncertainty), another face was equally likely followed by either of two vowels (intermediate cue uncertainty) and the third face was followed by all three vowels (high cue uncertainty). Our results suggest that pupil dilation in response to task‐relevant cues depends on the associated uncertainty, but only for large differences in the cue‐associated uncertainty. Additionally, in response to the auditory outcomes, the pupil dilation scaled negatively with the cue‐dependent probabilities, likely signalling the amount of surprise.
Bornean tropical forests recovering from logging at risk of regeneration failure
Authors: Bartholomew David C. , Hayward Robin , Burslem David F. R. P. , Bittencourt Paulo R. L. , Chapman Daniel , Bin Suis Mohd. Aminur Faiz , Nilus Reuben , O'Brien Michael J. , Reynolds Glen , Rowland Lucy , Banin Lindsay F. , Dent Daisy
Published: March 2024

Active restoration through silvicultural treatments (enrichment planting, cutting climbers and liberation thinning) is considered an important intervention in logged forests. However, its ability to enhance regeneration is key for long‐term recovery of logged forests, which remains poorly understood, particularly for the production and survival of seedlings in subsequent generations. To understand the long‐term impacts of logging and restoration we tracked the diversity, survival and traits of seedlings that germinated immediately after a mast fruiting in North Borneo in unlogged and logged forests 30–35 years after logging. We monitored 5119 seedlings from germination for ~1.5 years across a mixed landscape of unlogged forests (ULs), naturally regenerating logged forests (NR) and actively restored logged forests via rehabilitative silvicultural treatments (AR), 15–27 years after restoration. We measured 14 leaf, root and biomass allocation traits on 399 seedlings from 15 species. Soon after fruiting, UL and AR forests had higher seedling densities than NR forest, but survival was the lowest in AR forests in the first 6 months. Community composition differed among forest types; AR and NR forests had lower species richness and lower evenness than UL forests by 5–6 months post‐mast but did not differ between them. Differences in community composition altered community‐weighted mean trait values across forest types, with higher root biomass allocation in NR relative to UL forest. Traits influenced mortality ~3 months post‐mast, with more acquisitive traits and relative aboveground investment favoured in AR forests relative to UL forests. Our findings of reduced seedling survival and diversity suggest long time lags in post‐logging recruitment, particularly for some taxa. Active restoration of logged forests recovers initial seedling production, but elevated mortality in AR forests lowers the efficacy of active restoration to enhance recruitment or diversity of seedling communities. This suggests current active restoration practices may fail to overcome barriers to regeneration in logged forests, which may drive long‐term changes in future forest plant communities.
Downregulation of miR‐211 expression in the blood plasma of infertile men compared to the fertile controls
Authors: Naeimi Nasim , MohseniKouchesfehani Homa , Mahmoudzadeh‐Sagheb Hamidreza , Movahed Saeed , Moudi Bita , Asemirad Azam , Sheibak Nadia , Heidari Zahra
Published: March 2024

Objectives

Infertility is inability to conceive after 12 months of regular unprotected sex. MiRNA expression changes can serve as potential biomarkers for infertility in males due to impaired spermatogenesis. This research was conducted to measure the expression level of miR‐211 in plasma samples as a factor identifying infertility in comparison with the control group.

Methods

In this study, blood plasma were taken from the infertile men (n = 103) nonobstructive azoospermia (NOA) or severe oligozoospermia (SO) and the control group (n = 121). The expression of circulating miR‐211 in plasma was assessed by qRT‐PCR. A relative quantification strategy was adopted using the 2−ΔΔCT method to calculate the target miR‐211 expression level in both study groups.

Results

Plasma miR‐211 levels were significantly lower in infertile men compared to the control group (0.544 ± 0.028 and 1.203 ± 0.035, respectively, p < 0.001). Pearson's correlation analysis showed that miR‐211 expression level has a positive and significant correlation with sperm parameters, including sperm concentration, sperm total motility, progressive motility, and normal morphology (p < 0.001).

Conclusions

Decreased expression of miR‐211 in blood plasma seems to be associated with male infertility. This experiment showed that miR‐211 can be considered as a biomarker for evaluation, diagnosis, and confirmation of the results of semen analysis in male infertility.
Utility of positive core number on MRI‐ultrasound fusion targeted biopsy in combination with PI‐RADS scores for predicting unexpected extracapsular extension of clinically localized prostate cancer
Authors: Kobayashi Masaki , Matsuoka Yoh , Uehara Sho , Tanaka Hiroshi , Fujiwara Motohiro , Nakamura Yuki , Ishikawa Yudai , Fukuda Shohei , Waseda Yuma , Tanaka Hajime , Yoshida Soichiro , Fujii Yasuhisa
Published: March 2024

Objectives

To evaluate the utility of magnetic resonance imaging (MRI) and MRI‐ultrasound fusion targeted biopsy (TB) for predicting unexpected extracapsular extension (ECE) in clinically localized prostate cancer (CLPC).

Methods

This study enrolled 89 prostate cancer patients with one or more lesions showing a Prostate Imaging‐Reporting and Data System (PI‐RADS) score ≥3 but without morphological abnormality in the prostatic capsule on pre‐biopsy MRI. All patients underwent TB and systematic biopsy followed by radical prostatectomy (RP). Each lesion was examined by 3‐core TB, taking cores from each third of the lesion. The preoperative variables predictive of ECE were explored by referring to RP specimens in the lesion‐based analysis.

Results

Overall, 186 lesions, including 81 (43.5%), 73 (39.2%), and 32 (17.2%) with PI‐RADS 3, 4, and 5, respectively, were analyzed. One hundred and twenty‐two lesions (65.6%) were diagnosed as cancer on TB, and ECE was identified in 33 (17.7%) on the RP specimens. The positive TB core number was ≤2 in 129 lesions (69.4%) and three in 57 lesions (30.6%). On the multivariate analysis, PI‐RADS ≥4 (p = 0.049, odds ratio [OR] = 2.39) and three positive cores on TB (p = 0.005, OR = 3.07) were independent predictors of ECE. Lesions with PI‐RADS ≥4 and a positive TB core number of 3 had a significantly higher rate of ECE than those with PI‐RADS 3 and a positive TB core number ≤2 (37.5% vs. 7.8%, p < 0.001).

Conclusions

Positive TB core number in combination with PI‐RADS scores is helpful to predict unexpected ECE in CLPC.
Identification and clinical validation of the role of anoikis‐related genes in diabetic foot
Authors: Su Nan , Wang Jiwei , Zhang Hengrui , Jin Haoyong , Miao Baojian , Zhao Jiangli , Liu Xuchen , Li Chao , Wang Xinyu , Yang Ning
Published: March 2024

This study aims to investigate the role of anoikis‐related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis‐related genes (DE‐ARGs). GO analysis and KEGG analysis indicated that DE‐ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K‐Akt signalling pathway. Based on the LASSO and SVM‐RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM‐receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein‐coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.
Serum vitamin D is substantially reduced and predicts flares in diabetic retinopathy patients
Authors: Zhuang Yong , Zhuang Zihao , Cai Qingyan , Hu Xin , Huang Huibin
Published: March 2024

Aims/Introduction

Research has suggested that vitamin D deficiency is associated with diabetic retinopathy (DR). Our study aimed to determine whether vitamin D deficiency is the cause of diabetic retinopathy or if diabetic retinopathy reduces vitamin D levels.

Materials and Methods

Participants with type‐2 diabetes were recruited for this prospective observational clinical study and were divided into a diabetic group without retinopathy and a diabetic group with retinopathy, with additional healthy volunteers serving as a control group. The differences in clinical characteristics among the three groups were also compared. Patients without retinopathy were then followed for 1 year to monitor the incidence of diabetic retinopathy. After follow‐up, participants were divided into subgroups based on whether diabetic retinopathy occurred. The baseline data of the subgroups were compared, and the independent risk factors were analyzed.

Results

Vitamin D levels were generally low. Participants with diabetic retinopathy had significantly lower vitamin D levels than did those without retinopathy (P < 0.01). A comparison of the two subgroups revealed lower baseline vitamin D concentrations in the new‐DR subgroup than in the non‐DR subgroup (P < 0.01). Vitamin D deficiency and elevated HbA1c levels were found to be independent risk factors for diabetic retinopathy (OR = 0.935, 95% CI: 0.867–0.981, P = 0.006; OR = 2.208, 95% CI: 1.764–2.764, P < 0.01). The limit of vitamin D intake according to the receiver‐operating characteristic (ROC) curve was 26.01 ng/mL, and the area under the ROC curve was 0.603 (95% CI: 0.559–0.706, P = 0.002).

Conclusions

Vitamin D levels were significantly lower in patients diagnosed with diabetic retinopathy. More importantly, vitamin D deficiency may accelerate the onset of diabetic retinopathy.
Malignant ovarian and testicular germ cell tumors: Common characteristics but different prognoses
Authors: Sköld Camilla , Jansson Anna K , Glimelius Ingrid
Published: March 2024

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin‐based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long‐term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995–2022) and ovarian (1990–2018) GCTs. The 5‐year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non‐seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs—including de‐escalating adjuvant chemotherapy for low‐risk patients and implementing more standardized and intensive treatment protocols in cases of relapse—we can improve the prognosis and minimize long‐term side effects in ovarian GCT patients.
The Journal of Law and Society in context: a bibliometric analysis
Authors: BOULANGER CHRISTIAN , CREUTZFELDT NAOMI , HENDRY JENNIFER
Published: March 2024

On this, the occasion of its 50th anniversary, we employ a quantitative analysis of the Journal of Law and Society (JLS) to chart empirically the evolution of socio‐legal studies in the United Kingdom (UK). By tracing the influence(s) of the JLS upon the development of UK socio‐legal research, not only do we demonstrate a new mode of exploring knowledge production in the field of socio‐legal studies, but we also illustrate how computational methods can augment hermeneutical approaches to mapping socio‐legal trends. Through (a blend of) three different analytical approaches – descriptive analyses of bibliographic metadata, text‐linguistic analyses of a corpus of full‐text articles, and network analyses of citation graphs – we generate comparative information about the JLS since its inception in 1974. We then employ this data to interrogate the JLS’ own narratives; using predictions, ambitions, and statements of intent made by Editor‐in‐Chief Phil Thomas published either within or regarding the JLS, we present a map of the journal's role within, impact upon, and enduring contribution to UK socio‐legal studies. Finally, we discuss our results and propose future directions of the field.
Impact of feeding biochar sources in rohu (Labeo rohita): Evaluating the growth, nutrient absorption, carcass composition, haematology and mineral status
Authors: Khalid Muhammad Adnan , Hussain Syed Makhdoom , Ali Shafaqat , Ali Qasim , Rizwan Muhammad , Paray Bilal Ahamad , Sarker Pallab K. , Naeem Adan
Published: March 2024

Biochar, an organic carbonaceous matter, is a unique feed additive that is now being used in aquaculture industry to formulate a cost‐effective and eco‐friendly diet. This experiment (in door) was conducted over course of 90 days to determine the most effective form of biochar, produced from various sources, for supplementation in Moringa oleifera seed meal‐based diet. These sources were: farmyard manure biochar, parthenium biochar (PB), vegetable waste biochar, poultry waste biochar (PWB) and corncob waste biochar, added at 2 g/kg concentration to determine the effect of supplementation on the growth indices, nutrient absorption, carcass composition, haematology and mineral status of Labeo rohita (rohu) fingerlings. The research design consisted of six test diets with three replications (6 × 3) of each. Total of 270 fingerlings (6.30 ± 0.020 g) were fed at 5% body weight and 15 of them were kept in separate steel tanks. The results indicated that PWB was most effective in improving weight gain (285.58 ± 4.54%) and feed conversion ratio (1.060 ± 0.040) compared to control diet and other test diets. The same type of biochar (PWB) produced the best results for nutrient digestibility, that is, crude protein, crude fat and gross energy and carcass composition. In terms of haematology and mineral status, PWB showed the best results. In conclusion, it was found that PWB significantly enhanced (p < 0.05) L. rohita fingerling's growth, carcass composition, nutrient digestibility, haematological parameters (red blood cells, white blood cells, platelets and haemoglobin) and mineral composition (Ca, Na, P, Mg, Fe, Mn, Zn, K and Cu) whereas PB negatively affected all parameters. It is anticipated that the potential use of biochar will increase in aquaculture industry, as research on its incorporation in fish feeds is still limited.
Does urbanisation lead to parallel demographic shifts across the world in a cosmopolitan plant?
Authors: Caizergues Aude E. , Santangelo James S. , Ness Rob W. , Angeoletto Fabio , Anstett Daniel N. , Anstett Julia , Baena‐Diaz Fernanda , Carlen Elizabeth J. , Chaves Jaime A. , Comerford Mattheau S. , Dyson Karen , Falahati‐Anbaran Mohsen , Fellowes Mark D. E. , Hodgins Kathryn A. , Hood Glen Ray , Iñiguez‐Armijos Carlos , Kooyers Nicholas J. , Lázaro‐Lobo Adrián , Moles Angela T. , Munshi‐South Jason , Paule Juraj , Porth Ilga M. , Santiago‐Rosario Luis Y. , Whitney Kaitlin Stack , Tack Ayko J. M. , Johnson Marc T. J.
Published: March 2024

Urbanisation is occurring globally, leading to dramatic environmental changes that are altering the ecology and evolution of species. In particular, the expansion of human infrastructure and the loss and fragmentation of natural habitats in cities is predicted to increase genetic drift and reduce gene flow by reducing the size and connectivity of populations. Alternatively, the ‘urban facilitation model’ suggests that some species will have greater gene flow into and within cities leading to higher diversity and lower differentiation in urban populations. These alternative hypotheses have not been contrasted across multiple cities. Here, we used the genomic data from the GLobal Urban Evolution project (GLUE), to study the effects of urbanisation on non‐adaptive evolutionary processes of white clover (Trifolium repens) at a global scale. We found that white clover populations presented high genetic diversity and no evidence of reduced Ne linked to urbanisation. On the contrary, we found that urban populations were less likely to experience a recent decrease in effective population size than rural ones. In addition, we found little genetic structure among populations both globally and between urban and rural populations, which showed extensive gene flow between habitats. Interestingly, white clover displayed overall higher gene flow within urban areas than within rural habitats. Our study provides the largest comprehensive test of the demographic effects of urbanisation. Our results contrast with the common perception that heavily altered and fragmented urban environments will reduce the effective population size and genetic diversity of populations and contribute to their isolation.
The die‐hards, negotiators and migrants: Portraits of doctors' career pathways through specialisation
Authors: Rozario Shemona Y. , Farlie Melanie K. , Sarkar Mahbub , Lazarus Michelle D.
Published: March 2024

Introduction

Global workforce shortages in medical specialties strain healthcare systems, jeopardising patient outcomes. Enhancing recruitment strategies by supporting professional identity (PI) development may be one way to address this workforce gap—yet little research has explored this topic. The goal of the current study was to explore specialty‐specific recruitment through considering PI. As proposed causes of workforce shortages in anatomical pathology (AP) bear similarities to many other specialties, this study uses the field of AP as a model for specialist PI development and asks: (1) why, how and when do doctors choose to pursue AP training and (2) what can be learned from this for recruitment to AP and other specialties?

Methods

A qualitative research approach was undertaken using narrative inquiry. Interviews with junior doctors interested in AP, AP registrars and AP consultants from Australia and New Zealand were interpreted as stories via ‘re‐storying’. Narrative synthesis of participants' collective stories identified chronological key events (i.e. ‘turning points’) in choosing AP.

Results

Narrative synthesis resulted in identification of three portraits entering medical specialist training: (1) die‐hards, deciding upon initial exposure; (2) negotiators, choosing after comparing specialties; and (3) migrants, seeking to move away from non‐pathology specialties. The negotiators and migrants cemented their decision to pursue AP as a postgraduate doctor, whereas the die‐hards made this decision during medical school.

Conclusions

Given the similarities in portrait traits between AP and other specialties across the literature, our results suggest ways to support specialty recruitment using PI development. We propose a medical specialist recruitment framework to support the PI development of doctors with die‐hard, negotiator and migrant traits. Use of this framework could enhance current specialty‐specific recruitment approaches, particularly in fields challenged by workforce shortages.
Association between breakfast consumption, breakfast quality, mental health and quality of life in Turkish adolescents: A high school‐based cross‐sectional study
Authors: Gürbüz Murat , Bayram Hatice Merve , Kabayel Nazmiye , Türker Zeynep Serra , Şahin Şeyma , İçer Serap
Published: March 2024

This study aimed to determine the frequency of breakfast consumption and breakfast quality among adolescents and to evaluate the relationships between breakfast consumption, breakfast quality, mental health, and health‐related quality of life. This cross‐sectional study included 449 students from 17 high schools between December 2022 and May 2023. A face‐to‐face questionnaire measuring the frequency of breakfast consumption, Mediterranean diet quality index (KIDMED), health‐related quality of life (KIDSCREEN), and depression, anxiety and stress scales (DASS‐21) was performed. Of the students, 54.1% skipped breakfast 2 or more times a week and 75.9% had poor breakfast quality. There were significant differences in breakfast quality classification according to the frequency of breakfast consumption (p = 0.003). Breakfast consumption ≤1 time/week or 2–5 times/week was associated with depression, anxiety and low adherence to the Mediterranean diet. No relationship was observed between breakfast quality and stress, depression or anxiety (p = 0.620, p = 0.586, p = 0.539, respectively) or between breakfast quality and the KIDSCREEN‐27 subscales (p > 0.05). However, those eating poor‐quality breakfasts had better results in physical wellbeing (p = 0.022), psychological wellbeing (p = 0.024), autonomy and parent relations (p = 0.017) than breakfast‐skippers and also scored lower for depression, stress and anxiety (all p < 0.001). In conclusion, the frequency of breakfast consumption had a stronger association with reduced symptoms of stress, depression and anxiety, as well as improvements in all dimensions of health‐related quality of life, compared to the quality of breakfast consumed. Given the association of breakfast consumption with mental health outcomes in adolescents, our findings are of great importance, especially to parents, clinicians and nutritional educators.
The role of collaboration in educating the global pediatric anesthesia workforce
Authors: Nabukenya Mary T. , Newton Mark W. , Gray Rebecca M. , Kapoor Indu , Kuratani Norifumi , Moore Jolene , Rai Ekta , Evans Faye M.
Published: March 2024

An estimated 1.7 billion children and adolescents do not have access to safe and affordable surgical care, and the vast majority of these are located in low‐middle‐income countries (LMICs). Pediatric anesthesia, a specialized field that requires a diverse set of knowledge and skills, has seen various advancements over the years and has become well‐established in upper‐middle and high‐income countries. However, in LMICs, due to a multitude of factors including severe workforce shortages, this has not been the case. Collaborations play a vital role in increasing the capacity of pediatric anesthesiology educators and training the pediatric anesthesia workforce. These efforts directly increase access for children who require surgical intervention. Collaboration models can be operationalized through bidirectional knowledge sharing, training, resource allocation, research and innovation, quality improvement, networking, and advocacy. This article aims to highlight a few of these collaborative efforts. Specifically, the role that the World Federation of Societies of Anaesthesiologists, the Safer Anesthesia from Education program, the Asian Society of Pediatric Anaesthesiologists, Pediatric Anesthesia Training in Africa, the Paediatric Anaesthesia Network New Zealand, the Safe Pediatric Anesthesia Network and two WhatsApp™ groups (global ped anesthesia and the Pediatric Difficult Intubation Collaborative) have played in improving anesthesiology care for children.
The relationship between fear of old age, loneliness and death anxiety in adults
Authors: Çiftci Necmettin , Yildiz Metin , Durmuş Mustafa , Çoban Mahmut
Published: March 2024

Background

The increase in the number of elderly people in the world, individuals' perspectives on older adults, and false beliefs and ideas about old age negatively affect adults in terms of ageing. This study was conducted to determine the relationship between fear of old age, loneliness and death anxiety in adults.

Method

This study, which was designed in a correlational cross‐sectional descriptive model, was conducted with 1074 adult individuals living in one province in eastern Turkey. Data were collected using Personal Information Form, Fear of Old Age Scale, UCLA Loneliness Scale and Turkish Death Anxiety Scale. Data were analyzed using SPSS 25.0, AMOS 24.0, G*Power 3.1 statistical package programs.

Results

In our study, it was determined that the model created in line with the hypotheses was compatible and the model fit indices were within the desired limits as χ2/df = 4.737, root mean square error of approximation = 0.05, comparative fit index = 0.93, goodness‐of‐fit index = 0.92, adjusted goodness‐of‐fit index = 0.90, IFI = 0.93. There is a significant relationship between loneliness and death anxiety (P < 0.05). There is a significant relationship between loneliness and fear of old age (P < 0.05). There is a significant relationship between death anxiety and fear of old age (P < 0.05). It was determined that death anxiety has a mediating role in the effect of loneliness on fear of old age (95% confidence interval: 0.112–0.226; P < 0.05).

Conclusion

As the level of loneliness increases, the level of death anxiety and fear of old age increases. Fear of old age also increases in the mediating role of death anxiety. It is recommended to conduct intervention studies to reduce fear of old age. Longitudinal study on fear of old age is recommended.
Ocular biometry in rabbits using computed tomography
Authors: Goody Nicholas , Israeliantz Nicolas , Massidda Azzurra , Richardson Jenna , Blacklock Benjamin , Mitchell Jordan , Liuti Tiziana
Published: March 2024

Objective

To describe a repeatable method of measuring ocular structures and to establish ocular biometry reference ranges in adult domestic rabbits (Oryctolagus cuniculus) without medical history or imaging findings consistent with ophthalmic disease using a 64‐slice multidetector computed tomography scanner.

Procedure

In this retrospective and observational anatomic study, 100 eyes from 50 rabbits without medical history or imaging findings consistent with ophthalmic disease who received a head computed tomography scan were selected for measurement of globe length, width, and height using 3D multiplanar reconstruction. Lens width and length, the anteroposterior length of the anterior and vitreous chambers, and attenuation of the lens and vitreous chamber were collected. These parameters were compared against age, sex, weight, body condition, and ear conformation.

Results

A reference guide was established, with globe width being the largest dimension (18.03 ± 0.81 mm), followed by height (17.18 ± 0.69 mm) and then length (16.64 ± 0.66 mm). Increased weight was associated with an increase in globe height (p = 2.43 × 10−5), length (p = 1.63 × 10−4), and width (p = 7.0 × 10−3). Increased age was associated with increased lens attenuation (p = 1.28 × 10−7) and increased transverse lens width (p = 1.64 × 10−3). Inter‐ and intra‐observer agreement was excellent.

Conclusions

CT is a reliable modality for measurement of ocular biometry dimensions in rabbits. These reference values can be applied to aid in identifying diseases that affect the dimensions of the ocular structures in rabbits over 18 months of age.
Multicenter evaluation of the
Toxoplasma gondii
Real-TM (Sacace) kit performance for the molecular diagnosis of toxoplasmosis
Authors: Guitard Juliette , Brenier-Pinchart Marie-Pierre , Varlet-Marie Emmanuelle , Dalle Frédéric , Rouges Celia , Argy Nicolas , Bonhomme Julie , Capitaine Agathe , Guégan Hélène , Lavergne Rose-Anne , Dardé Marie-Laure , Pelloux Hervé , Robert-Gangneux Florence , Yera Hélène , Sterkers Yvon
Published: March 2024

The molecular detection of
Toxoplasma gondii
DNA is a key tool for the diagnosis of disseminated and congenital toxoplasmosis. This multicentric study from the Molecular Biology Pole of the French National Reference Center for toxoplasmosis aimed to evaluate
Toxoplasma gondii
Real-TM PCR kit (Sacace). The study compared the analytical and clinical performances of this PCR assay with the reference PCRs used in proficient laboratories. PCR efficiencies varied from 90% to 112%; linearity zone extended over four log units (R
2
> 0.99) and limit of detection varied from 0.01 to ≤1 Tg/mL depending on the center. Determined on 173 cryopreserved DNAs from a large range of clinical specimens, clinical sensitivity was 100% [106/106; 95 confidence interval (CI): 96.5%–100%] and specificity was 100% (67/67; 95 CI: 94.6%–100%). The study revealed two potential limitations of the Sacace PCR assay: the first was the inconsistency of the internal control (IC) when added to the PCR mixture. This point was not found under routine conditions when the IC was added during the extraction step. The second is a lack of practicality, as the mixture is distributed over several vials, requiring numerous pipetting operations. Overall, this study provides useful information for the molecular diagnosis of toxoplasmosis; the analytical and clinical performances of the Sacace PCR kit were satisfactory, the kit having sensitivity and specificity similar to those of expert center methods and being able to detect low parasite loads, at levels where multiplicative analysis gives inconsistently positive results. Finally, the study recommends multiplicative analysis in particular for amniotic fluids, aqueous humor, and other single specimens.
Tracing the STING exocytosis pathway during herpes viruses infection
Authors: Dogrammatzis Christos , Saud Rabina , Waisner Hope , Lasnier Sarah , Suma Sreenath Muraleedharan , Grieshaber Brandon , Kalamvoki Maria
Published: March 2024

The STimulator of INterferon Genes (STING) constitutes a major DNA-sensing pathway that restricts HSV-1 infection in different models by activating type I interferon and pro-inflammatory responses. To counteract STING, HSV-1 has evolved numerous strategies including mechanisms to interfere with its oligomerization, post-translational modifications, and downstream signaling. Previously, we demonstrated that STING is packaged in extracellular vesicles (EVs) produced from HSV-1-infected cells. These EVs activated antiviral responses in uninfected recipient cells and suppressed a subsequent HSV-1 infection in a STING-dependent manner. Here, we provide information on the packaging of STING in EVs and its exocytosis. We found that STING exocytosis did not occur in CD63 knockdown cells supporting that STING follows the CD63 exocytosis pathway. Consistently, we found that STING co-localized with CD63 in cytoplasmic globular structures and exosomal STING and CD63 co-fractionated. Both golgicide A and brefeldin A prevented STING exocytosis during HSV-1 infection suggesting that STING trafficking through the Golgi is required. A STING ligand was insufficient for STING exocytosis, and downstream signaling through TBK1 was not required. However, STING palmitoylation and tethering to the ER by STIM1 were required for STING exocytosis. Finally, we found that HSV-1 replication/late gene expression triggered CD63 exocytosis that was required for STING exocytosis. Surprisingly, HSV-2 strain G did not trigger CD63 or STING exocytosis as opposed to VZV and HCMV. Also, EVs from HSV-1(F)- and HSV-2(G)-infected cells displayed differences in their ability to restrict these viruses. Overall, STING exocytosis is induced by certain viruses and shapes the microenvironment of infection.

IMPORTANCE

Extracellular vesicles (EVs) are released by all types of cells as they constitute a major mechanism of intercellular communication. The packaging of specific cargo in EVs and the pathway of exocytosis are not fully understood. STING is a sensor of a broad spectrum of pathogens and a key component of innate immunity. STING exocytosis during HSV-1 infection has been an intriguing observation, raising questions of whether this is a virus-induced process, the purpose it serves, and whether it is observed after infection with other viruses. Here, we have provided insights into the pathway of STING exocytosis and determined factors involved. STING exocytosis is a virus-induced process and not a response of the host to the infection. Besides HSV-1, other herpes viruses triggered STING exocytosis, but HSV-2(G) did not. HSV-1 EVs displayed different restriction capabilities compared with HSV-2(G) EVs. Overall, STING exocytosis is triggered by viruses to shape the microenvironment of infection.
Control of three-carbon amino acid homeostasis by promiscuous importers and exporters in
Bacillus subtilis
: role of the “sleeping beauty” amino acid exporters
Authors: Warneke Robert , Herzberg Christina , Daniel Richard , Hormes Björn , Stülke Jörg
Published: March 2024

The Gram-positive model bacterium
Bacillus subtilis
can acquire amino acids by import,
de novo
biosynthesis, or degradation of proteins and peptides. The accumulation of several amino acids inhibits the growth of
B. subtilis
, probably due to misincorporation into cellular macromolecules such as proteins or peptidoglycan or due to interference with other amino acid biosynthetic pathways. Here, we studied the adaptation of
B. subtilis
to toxic concentrations of the three-carbon amino acids L-alanine, β-alanine, and 2,3-diaminopropionic acid, as well as the two-carbon amino acid glycine. Resistance to the non-proteinogenic amino acid β-alanine, which is a precursor for coenzyme A biosynthesis, is achieved by mutations that either activate a cryptic amino acid exporter, AexA (previously YdeD), or inactivate the amino acid importers AimA, AimB (previously YbxG), and BcaP. The
aexA
gene is very poorly expressed under most conditions studied. However, mutations affecting the transcription factor AerA (previously YdeC) can result in strong constitutive
aexA
expression. AexA is the first characterized member of a group of amino acid exporters in
B. subtilis
, which are all very poorly expressed. Therefore, we suggest to call this group “sleeping beauty amino acid exporters.” 2,3-Diaminopropionic acid can also be exported by AexA, and this amino acid also seems to be a natural substrate of AerA/AexA, as it can cause a slight but significant induction of
aexA
expression, and AexA also provides some natural resistance toward 2,3-diaminopropionic acid. Moreover, our work shows how low-specificity amino acid transporters contribute to amino acid homeostasis in
B. subtilis
.

IMPORTANCE

Even though
Bacillus subtilis
is one of the most-studied bacteria, amino acid homeostasis in this organism is not fully understood. We have identified import and export systems for the C2 and C3 amino acids. Our work demonstrates that the responsible amino acid permeases contribute in a rather promiscuitive way to amino acid uptake. In addition, we have discovered AexA, the first member of a group of very poorly expressed amino acid exporters in
B. subtilis
that we call “sleeping beauty amino acid exporters.” The expression of these transporters is typically triggered by mutations in corresponding regulator genes that are acquired upon exposure to toxic amino acids. These exporters are ubiquitous in all domains of life. It is tempting to speculate that many of them are not expressed until the cells experience selective pressure by toxic compounds, and they protect the cells from rare but potentially dangerous encounters with such compounds.
The inner membrane protein YhiM links copper and CpxAR envelope stress responses in uropathogenic
E. coli
Authors: Saenkham-Huntsinger Panatda , Ritter Matthew , Donati George L. , Mitchell Angela M. , Subashchandrabose Sargurunathan
Published: March 2024

Urinary tract infection (UTI) is a ubiquitous infectious condition, and uropathogenic
Escherichia coli
(UPEC) is the predominant causative agent of UTI. Copper (Cu) is implicated in innate immunity, including against UPEC. Cu is a trace element utilized as a co-factor, but excess Cu is toxic due to mismetalation of non-cognate proteins.
E. coli
precisely regulates Cu homeostasis via efflux systems. However, Cu import mechanisms into the bacterial cell are not clear. We hypothesized that Cu import defective mutants would exhibit increased resistance to Cu. This hypothesis was tested in a forward genetic screen with transposon (Tn
5
) insertion mutants in UPEC strain CFT073, and we identified 32 unique Cu-resistant mutants. Transposon and defined mutants lacking
yhiM
, which encodes a hypothetical inner membrane protein, were more resistant to Cu than parental strain. Loss of YhiM led to decreased cellular Cu content and increased expression of
copA
, encoding a Cu efflux pump. The CpxAR envelope stress response system was activated in the
ΔyhiM
mutant as indicated by increased expression of
cpxP
. Transcription of
yhiM
was regulated by CueR and CpxR, and the CpxAR system was essential for increased Cu resistance in the
ΔyhiM
mutant. Importantly, activation of CpxAR system in the
ΔyhiM
mutant was independent of NlpE, a known activator of this system. YhiM was required for optimal fitness of UPEC in a mouse model of UTI. Our findings demonstrate that YhiM is a critical mediator of Cu homeostasis and links bacterial adaptation to Cu stress with the CpxAR-dependent envelope stress response in UPEC.

IMPORTANCE

UPEC is a common bacterial infection. Bacterial pathogens are exposed to host-derived Cu during infection, including UTI. Here, we describe detection of genes involved in Cu homeostasis in UPEC. A UPEC mutant lacking YhiM, a membrane protein, exhibited dramatic increase in resistance to Cu. Our study demonstrates YhiM as a nexus between Cu stress and the CpxAR-dependent envelope stress response system. Importantly, our findings establish NlpE-independent activation of CpxAR system during Cu stress in UPEC. Collectively, YhiM emerges as a critical mediator of Cu homeostasis in UPEC and highlights the interlinked nature of bacterial adaptation to survival during Cu and envelope stress.
Supplemental Material: Exceptional preservation of a marine tapeworm tentacle in Cretaceous amber
Authors: Luo Cihang , Wang Bo , al. et
Published: March 2024

Detailed description and discussion of the armature pattern of the fossil, Figures S1–S4, and Micro-CT Videos S1–S3.  
Supplemental Material: Thick- and thin-skinned contractional styles and the tectonic evolution of the northern Sangre de Cristo Mountains, Colorado, USA
Authors: Lindsey David A. , Caine Jonathan Saul
Published: March 2024

Tables showing locations of cross-sections and data sources (S1) and measurements of foliations and fault slip data (S2). 
Identical anatomy, different symptoms: a comparative case study of median arcuate ligament syndrome in monozygotic twins
Authors: Anthony Lakmali , Gillies Madeline , Bayat Iman
Published: March 2024

Median arcuate ligament syndrome (MALS) is a rare clinical entity arising from the extrinsic compression of the coeliac axis by the median arcuate ligament. In this report, we detail a unique presentation involving monozygotic twins, both of whom demonstrated anatomical extrinsic compression of the coeliac axis by the median arcuate ligament. Intriguingly, only one twin manifested clinical symptoms consistent with MALS, despite comparable anatomical compression of the coeliac axis observed in both. This case highlights the potential interplay of a genetic or anatomical predisposition to coeliac axis compression and secondary, possibly environmental, factors that lead to the development of clinical symptoms. In this report, we explore various determinants potentially influencing symptomatology in MALS and advocate for the publication of similar case studies to further elucidate this rare condition.
Changes in medical student attendance and its impact on student educational outcomes: a systematic review protocol
Authors: Nagappan Palaniappan Ganesh , Brown Samuel , McManus Alex , Sayers Sarah , Absar Shazia , Tan Sapphire Rou Xi , Kuhn Isla , Lau Edward , Tulinius Charlotte
Published: March 2024

Introduction

The COVID-19 pandemic has had a significant impact on medical education, with many institutions shifting to online learning to ensure the safety of students and staff. However, there has been a decline in in-person attendance at medical schools across the UK and worldwide following the relaxation of social distancing rules and the reinstation of in-person teaching. Importantly, this trend has been observed prior to the pandemic. While reflected within the literature, there is currently no systematic review describing these changes. We aim to find out how medical students’ attendance is changing as documented within the literature and its impact on their educational outcomes.

Methods and analysis

This systematic review will follow the guidelines of the Centre of Research and Dissemination, Meta-analyses of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We will search the major databases of Medline via Ovid, Embase via Ovid, Scopus, Web of Science, British Education Index via EBSCOhost and ERIC via EBSCOhost.

Two reviewers will independently screen each paper and extract data, with a third reviewer for dispute resolution. All studies reporting on medical students from various universities, both graduate and undergraduate and describing changes in attendance and/or students‘ educational outcomes will be included. Risk of bias in individual studies will be assessed using the Newcastle-Ottawa Scale and confidence in cumulative evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research approach. A narrative synthesis of the findings from all included studies will be reported.

Ethics and dissemination

Ethical approval is not required for this systematic review of existing publicly available literature. We will subsequently aim to publish the results of this systematic review in a peer-reviewed journal.
Impact of evidence-based guidelines on healthcare utilisation and costs for disc related sciatica in the Netherlands: a population-based, cross-sectional study
Authors: van Munster Juliëtte , Noordenbos Mark W , Halperin I J Y , van den Hout Wilbert B , van Benthem Peter Paul , Seinen Ingrid , Moojen Wouter A , Peul Wilco
Published: March 2024

Objective

The aim of this study was to assess the impact of high-quality evidence supporting surgical treatment of lumbar disc herniation (LDH) on healthcare practice in the Netherlands by examining changes in healthcare utilisation, including the timing of surgery, and the healthcare costs for patients with LDH.

Design

A retrospective, cross-sectional study was performed using population-based, longitudinal data obtained from the Dutch Healthcare Authority (2007–2020) and NIVEL’s primary care (2012–2020) administrative databases.

Setting

The study was conducted within the healthcare system of the Netherlands.

Participants

We included adults (≥18 years) who visited a Dutch hospital or a general practitioner (GP) for lumbar degenerative disc disease. Patients with LDH were identified based on registered diagnosis code, type of surgery (discectomy) and age (<56 years).

Main outcome measures

The primary outcome measure was the difference in the annual number of LDH procedures following the publication of evidence-based guidelines in 2009 (comparing the periods 2007–2009 to 2017–2019). Secondary outcome measures focused on the timing of surgery and associated healthcare costs. To validate the outcomes, secondary outcomes also include the number of discectomies and the number of procedures in the younger age group (discectomies, laminectomies, and fusion surgery).

Results

The number of patients suffering from LDH increased from 55 581 to 68 997 (+24%) between 2007 and 2019. A decrease was observed in the annual number of LDH procedures (−18%), in the number of discectomies (−22%) and in the number of procedures for patients aged <56 years (−18%). This resulted in lower healthcare costs by €10.5 million annually. In 2012, 31% of all patients <56 years had surgery before 12 weeks from diagnosis at the GP, whereas 20% did in 2019.

Conclusions

Healthcare utilisation for LDH changed tremendously in the Netherlands between 2007 and 2020 and seemed to be associated with the publication and implementation of evidence-based guidelines. The observed decrease in the number of procedures has been accompanied by a corresponding reduction in healthcare costs. These findings underscore the importance of adhering to evidence-based guidelines to optimise the management of patients with LDH.
Prevalence and predictors of lifetime amphetamine use among in-school adolescents in Sierra Leone.
Authors: Osborne Augustus , Aboagye Richard Gyan , Olorunsaiye Comfort Z , James Peter Bai , Bangura Camilla , Seidu Abdul-Aziz , Kangbai Jia B , Ahinkorah Bright Opoku
Published: March 2024

Objective

This study examined the prevalence of amphetamine use and its associated factors among in-school adolescents in Sierra Leone.

Design

Data for the study was sourced from the 2017 Sierra Leone Global School-based Health Survey. Percentages with confidence intervals (CIs) were used to present the prevalence of amphetamine use among in-school adolescents. A multivariable binary logistic regression analysis was employed to examine the factors associated with amphetamine use. The results were presented using adjusted odds ratios (aORs) with 95% CIs.

Setting

Sierra Leone.

Participants

A weighted sample of 1,314 in-school adolescents in Sierra Leone.

Outcome measure

Lifetime amphetamine use.

Results

The prevalence of amphetamine use was 6.1% (3.9%–9.5%). In-school adolescents who planned suicide were more likely to use amphetamine compared with those who did not (aOR 2.54; 95% CI 1.02 to 6.31). Also, the odds of amphetamine use were higher among in-school adolescents who received support from their peers (aOR 3.19, 95% CI 1.71 to 5.96), consumed alcohol (aOR 4.85, 95% CI 2.61 to 9.03), and those who had previously used marijuana (aOR 13.31, 95% CI 6.61 to 28.78) compared with those who did not receive any support, never consumed alcohol, and never used marijuana, respectively.

Conclusion

Amphetamine use is prevalent among in-school adolescents in Sierra Leone. There is a need to implement comprehensive public health policies that extend beyond school-based psychobehavioural therapies. These policies should specifically address the considerable risk factors associated with amphetamine use among in-school adolescents in Sierra Leone.