bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of ultrasound assessment of the rectus femoris muscle thickness: intra-rater, inter-rater, and inter-day analysis accounting for age and sex
Authors: Stausholm Martin Bjørn , da Silva Katielle Rodrigues , Inácio Pedro Augusto , de Sá Filho Alberto Souza , Lopes-Martins Pedro Sardinha Leonardo , Bjordal Jan Magnus , Leonardo Patrícia Sardinha , Lopes-Martins Rodrigo Alvaro B.
Published: November 2024

Background

The rectus femoris muscle plays an important role in maintaining lower limb stability and biomechanical control during basic physical activities. Both reduced quadriceps strength and decreased muscle thickness of the rectus femoris, as measured by ultrasound, are associated with an increased risk of falls in older adults. We estimated the relative and absolute intra-rater, inter-rater, and inter-day reliability of the procedure.

Methods

A female biologist and a male physical educator, both holding a master’s degree in human movement and rehabilitation, captured ultrasound images of the right rectus femoris muscle in 106 healthy participants (58 females and 48 males), aged 18 to 73 years. Each rater captured three images per participant during each visit, with two visits 7 to 10 days apart. A third person subsequently measured the muscle thickness. We calculated the Intraclass Correlation Coefficients (ICC) using a two-way random model and determined the 95% minimal detectable difference (MDD).

Results

The mean muscle thickness was 2.12 cm. The reliability based on single measurements was as follows: the intra-rater ICC for raters A and B was 0.998 at both visits (MDDs: 0.074–0.082 cm). The inter-rater ICC was 0.976 at visit 1 and 0.977 at visit 2 (MDDs: 0.269–0.270 cm). The inter-day ICC was 0.973 for rater A and 0.972 for rater B (MDDs: 0.286–0.291 cm). Sensitivity analyses accounting for age, sex, and the use of mean measurements produced similar results. The results were homoscedastic.

Conclusions

The rectus femoris muscle thickness was measured with good reliability using ultrasonography across all the settings.
Mucinous adenocarcinoma in kidneys with developmental anomalies - a report of two cases
Authors: Gali Kasi Viswanath , Chawla Arun , Surag K. R. , Bhaskara Sunil Pillai , Hegde Padmaraj
Published: November 2024

Background

Primary mucinous adenocarcinomas of the kidney are rare and pose a challenge for preoperative diagnosis. The histogenesis of these tumours remains largely unknown, with three proposed theories: chronic irritation, differentiation of celomic epithelium, and kidney maldevelopment. Here, we present two cases of renal mucinous adenocarcinoma in patients with developmental renal anomalies, specifically a duplex collecting system and a horseshoe kidney.

Case Presentation

First, A 50-year-old male presented with loin pain and jelly-like discharge in urine with a duplex collecting system and gross hydronephrosis of the upper moiety on imaging. The patient underwent upper polar nephrectomy with controlled drainage of 1.5 L of mucinous fluid. Histopathology was suggestive of mucinous borderline cystic neoplasm with invasive microcarcinoma. The patient presented one year later, with a hydronephrotic lower moiety of the left kidney and a rectus abdominis mass. Fine needle aspiration biopsy of the mass revealed papillary adenocarcinoma with histological resemblance to the renal pelvis lesion, establishing it as a metastasis from the primary renal malignancy. Second, A 53-year-old male who had undergone right laparoscopic cyst deroofing for a symptomatic renal cyst, whose postoperative histology revealed findings consistent with mucinous adenocarcinoma, presented with flank pain and palpable retroperitoneal mass. Imaging revealed a horseshoe kidney morphology with a large multilobulated hypodense non-enhancing cystic lesion arising from the right kidney. Cyst excision with right open radical nephrectomy was performed. Gross examination revealed multiple cystic spaces replacing renal parenchyma, filled with gelatinous material. Microscopy was suggestive of recurrent mucinous adenocarcinoma.

Conclusions

Renal mucinous cystadenocarcinomas can be associated with anomalous kidneys. Definitive diagnosis relies on histopathology, and these tumours are recognized for their aggressive nature. Complete resection is the preferred treatment, but further studies are needed to assess the efficacy of adjuvant treatment, given the poor prognosis and high likelihood of recurrence.

Clinical trial number

Not applicable.
Effect of oxyresveratrol under in vitro lipopolysaccharide-induced periodontitis environment
Authors: Ye Ju Ri , Park Seung Hwan , Kang Sang Wook , Kwack Kyu Hwan , Chae Yong Kwon , Lee Hyo-Seol , Choi Sung Chul , Nam Ok Hyung
Published: November 2024

Background

Oxyresveratrol is the main constituent of mulberries and has many bioactive properties beneficial to human health. The purpose of this study was to assess the anti-inflammatory effects of oxyresveratrol on in vitro periodontitis model.

Methods

Human periodontal ligament cells were treated with oxyresveratrol (0, 10, and 20 µg/mL) for 72 h. Cell viability and flow cytometry assays were performed. To investigate anti-inflammatory effect of oxyresveratrol on periodontal inflammation, nitric oxide production under lipopolysaccharide stimulation was assessed. Next, expression of biomarkers associated periodontal inflammation was evaluated. Scratch wound assay was performed to evaluate cell migration/proliferation potential of oxyresveratrol under lipopolysaccharide stimulation.

Results

Periodontal ligament cell toxicity was not observed in oxyresveratrol treatment. Oxyresveratrol treatment significantly inhibited nitric oxide production and reduced MMP-2, MMP-9, TNF-α, IL-6, and IL-8 expressions after lipopolysaccharide stimulation. Regarding cell migration/proliferation, open wound area in oxyresveratrol (33.28 ± 6.80%) was the lowest (p < 0.05).

Conclusions

Within the limits of this study, oxyresveratrol inhibited lipopolysaccharide-induced inflammation in periodontal ligament cells and promoted periodontal ligament cell migration/proliferation. These findings suggest that oxyresveratrol could be valuable for the management of periodontal diseases.
Microstomia is associated with functional impairment and is a poor prognostic factor in systemic sclerosis – a single center observational study with survival analysis
Authors: Filipánits Kristóf , Nagy Gabriella , Varjú Cecília , Czirják László , Minier Tünde
Published: November 2024

Background

Objectives were to assess the mouth opening ability (MOA) among patients with systemic sclerosis (SSc) in comparison to a healthy control population. The impact of microstomia (decrease in any of the MOA parameters) on physical performance and long-term survival was also investigated.

Methods

Interincisal (ID), interlabial (LD), the intercommissural distances at both opened mouth and closed mouth (OW, CW) and the oral area (OA) and circumference (OC) all were assessed in 131 SSc patients. Microstomia was defined based on the oral aperture values of a healthy control group (n = 63) with similar median age and sex distribution. Tests evaluating functional performance were performed. Survival analysis by univariate and multivariate Cox regression analysis was performed.

Results

Microstomia was present in 56.5% of the entire SSc cohort. Patients with microstomia had higher number of contractures compared to those with preserved oral aperture parameters (median 10 vs. 7, p < 0.01). LD, OA and OC correlated negatively with the number of joint contractures, both in the entire SSc cohort and separately in the diffuse (dcSSc) and limited cutaneous subsets (lcSSc), (rho: between − 0.267 and − 0.516, p < 0.05). Reduced ID was associated with worse Health Assessment Questionnaire Disability Index (HAQ-DI) only in dcSSc while reduced LD was linked to increased HAQ-DI scores in both SSc subsets. Decreased OA upon enrollment was associated with an increased risk in mortality by multivariate Cox regression analysis (HR: 2.74; 95% CI, 1.15–6.53).

Conclusions

Microstomia was associated with joint damage, and higher overall disability based on HAQ-DI. Interlabial distance was a beneficial, convenient measurable parameter to characterize oral aperture. Oral area was an independent poor prognostic factor regarding long-term survival.
Clinicians’ experiences of obtaining informed consent for research and treatment: a nested qualitative study from Pakistan
Authors: Memon Rakhshi , Asif Muqaddas , Shah Bushra Ali , Kiran Tayyeba , Khoso Ameer B , Tofique Sehrish , Miah Jahanara , Ahmad Ayesha , Chaudhry Imran , Chaudhry Nasim , Husain Nusrat , Edwards Sarah J L
Published: November 2024

Background

Informed consent is considered to be the standard method for respecting the autonomy of individual participants in research and practices and is thought to be based on several conditions: (1) providing information on the purpose of the research or a specific treatment, what it will entail, (2) the participants being mentally competent to understand the information and weigh it in the balance, and (3) the participants to be free from coercion. While there are studies of informed consent in other countries, especially Low and Middle Income Countries (LMICs), this study explored the experiences of clinicians regarding the process of obtaining informed consent to participate in a Randomised Controlled Trial (RCT) in particular and treatment in general in healthcare settings, both general and mental health, specifically focusing on the tension between individualistic concept of autonomy and collectivist values in cultures such as Pakistan.

Methods

Qualitative interviews with 20 clinicians from healthcare settings in Pakistan who also served as recruiters in a suicide prevention RCT in Pakistan. The interviews were guided by semi-structured topic guide. All interviews were audio-recorded and transcribed verbatim.

Results

The interviews revealed that shared decision making was more morally important than individual autonomy, the role of the family played a dominant part in the consent-taking procedure, the decision of the elder and/or family patriarch took prominence, and that clinician-researchers encountered significant challenges in consent process in Pakistan, while recruiting patients into the trial as well as during routine treatment processes in healthcare settings. Four distinct themes emerged which were (1) Family deciding for patients, (2) Benefits of involving family in consent process, (3) Gender disparity in consent process, (4) Challenges experienced by clinician-researchers during consent process in Pakistan.

Conclusions

The concept of consent is generally considered important in many cultures, however, there are two strands of understanding. There seems to be consensus that participant agreement is necessary to protect the participant but with regards to autonomy there are significant cultural differences whether it is the right for autonomy of the individual (individualistic concept) or family, community, or expert authority in other cultures. In Pakistan clinician-researchers sometimes preferred one approach and sometimes the other as they appreciated the interests of the patient to be.
Efficacy of attractive targeted sugar bait stations against malaria in Western Province Zambia: epidemiological findings from a two-arm cluster randomized phase III trial
Authors: Ashton Ruth A. , Saili Kochelani , Chishya Chama , Banda Yikona Handrinah , Arnzen Annie , Orange Erica , Chitoshi Chanda , Chulu John , Tobolo Titus , Ndalama Frank , Kyomuhangi Irene , Ngulube Willy , Moonga Hawela , Chirwa Jacob , Slutsker Laurence , Wagman Joseph , Chanda Javan , Miller John , Silumbe Kafula , Hamainza Busiku , Eisele Thomas P. , Yukich Joshua , Littrell Megan
Published: November 2024

Background

Attractive targeted sugar bait (ATSB) stations containing bait (to attract) and ingestion toxicant (to kill) sugar-foraging mosquitoes are hypothesized to reduce malaria transmission by shortening the lifespan of Anopheles vectors.

Methods

A two-arm cluster-randomized controlled trial (cRCT) was conducted in Western Province Zambia. Seventy clusters of 250–350 households were assigned (1:1) by restricted randomization to an intervention arm (ATSB) or control arm (no ATSB) in the context of standard of care vector control (insecticide-treated nets and/or indoor residual spraying). Two ATSB stations (Westham Sarabi, 0.11% dinotefuran w/w) were maintained on exterior walls of eligible household structures for a 7-month deployment period (December-June) during the high malaria transmission season. The primary outcome was clinical malaria incidence among two consecutive seasonal cohorts of children aged 1–14 years, followed-up monthly from January-June in 2022 and 2023. Secondary outcome was Plasmodium falciparum prevalence among individuals aged over six months. Analysis compared clinical malaria incidence and prevalence between arms among the intention-to-treat population.

Results

ATSB coverage, assessed by cross-sectional survey, was 98.3% in March–April 2022 and 89.5% in March–April 2023. 4494 children contributed any follow-up time to the cohort, with 2313 incident malaria cases in the intervention arm (1.28 per child per six-month transmission season), and 2449 in the control arm (1.38 per child-season). The incidence rate ratio between the two arms was 0.91 (95% CI 0.72–1.15, p = 0.42). 2536 individuals participated in cross-sectional surveys, with prevalence of P. falciparum 50.7% in the intervention arm and 53.5% in the control arm. The odds ratio between the two arms was 0.89 (95% CI 0.66–1.18, p = 0.42). Secondary covariable-adjusted and subgroup analyses did not substantially alter the findings. No serious adverse events associated with the intervention were reported.

Conclusions

Two ATSB stations deployed per eligible structure for two consecutive transmission seasons did not result in a statistically significant reduction in clinical malaria incidence among children aged 1–14 years or in P. falciparum prevalence in rural western Zambia. Further studies are needed to assess the efficacy of ATSB stations in different settings and with different deployment strategies.

Trial registration

The trial is registered with Clinicaltrials.gov (NCT04800055).
Unpacking occupational and sex divides to understand the moderate progress in life expectancy in recent years (France, 2010’s)
Authors: Merville Ophélie , Bonnet Florian , Launoy Guy , Camarda Carlo Giovanni , Cambois Emmanuelle
Published: November 2024

Purpose

The growth in life expectancy (LE) slows down recently in several high-income countries. Among the underlying dynamics, uneven progress in LE across social groups has been pointed out. However, these dynamics has not been extensively studied, partly due to data limitations. In this paper, we explore this area for the 2010 decade using recent French data.

Methods

We utilize the recent change in French census mortality follow-up data (EDP) and apply P-spline models to estimate LEs across five occupational classes (OCs) and indicators of lifespan heterogeneity (edagger) within these OCs, for seven triennial periods (2011-2013 to 2017-2019).

Results

First, we found a similar ranking of OCs along the LE gradient over time and across sexes, from manual workers to higher-level OCs. Noteworthy, the lowest LE in women overlaps with the highest one in men drawing a sex-OC gradient. Second, we observe varying progress of LEs. In women, LE increases in higher-level OCs meanwhile it levels off in manual workers, so that the OCs gap widens (up to 3.4 years in 2017-2019). Conversely, in men LE stalls in higher-level OCs and increases in manual workers so that the gap, which is much larger than in women (+5.7 years in 2017-2019), is tending to narrow. Finally, the lifespan homogenizes in OCs only when LE is low.

Conclusion

Overall, the limited LE progress in France results from LE stalling in the middle of the sex-OC gradient, though LE increases at both ends. At the lower end, LE progress and lifespan homogenization suggest that laggards benefit recently improvements achieved earlier in other OCs. At the upper end, LE progress may come from a vanguard group within higher-lever OC, benefiting new sources of improvements. These findings underscore the need for further research to explore the diverse mortality dynamics coexisting in the current health landscape.
Nanotechnology in healthcare, and its safety and environmental risks
Authors: Ma Xiaohan , Tian Yaxin , Yang Ren , Wang Haowei , Allahou Latifa W. , Chang Jinke , Williams Gareth , Knowles Jonathan C. , Poma Alessandro
Published: November 2024

Nanotechnology holds immense promise in revolutionising healthcare, offering unprecedented opportunities in diagnostics, drug delivery, cancer therapy, and combating infectious diseases. This review explores the multifaceted landscape of nanotechnology in healthcare while addressing the critical aspects of safety and environmental risks associated with its widespread application. Beginning with an introduction to the integration of nanotechnology in healthcare, we first delved into its categorisation and various materials employed, setting the stage for a comprehensive understanding of its potential. We then proceeded to elucidate the diverse healthcare applications of nanotechnology, spanning medical diagnostics, tissue engineering, targeted drug delivery, gene delivery, cancer therapy, and the development of antimicrobial agents. The discussion extended to the current situation surrounding the clinical translation and commercialisation of these cutting-edge technologies, focusing on the nanotechnology-based healthcare products that have been approved globally to date. We also discussed the safety considerations of nanomaterials, both in terms of human health and environmental impact. We presented the in vivo health risks associated with nanomaterial exposure, in relation with transport mechanisms, oxidative stress, and physical interactions. Moreover, we highlighted the environmental risks, acknowledging the potential implications on ecosystems and biodiversity. Lastly, we strived to offer insights into the current regulatory landscape governing nanotechnology in healthcare across different regions globally. By synthesising these diverse perspectives, we underscore the imperative of balancing innovation with safety and environmental stewardship, while charting a path forward for the responsible integration of nanotechnology in healthcare.

Graphical abstract
Depression in patients with chronic otolaryngology symptoms – A vicious cycle
Authors: Khadilkar Meera Niranjan , K. Keshava Pai , Rai Thripthi , Shenoy Vijendra , Dosemane Deviprasad
Published: November 2024

Background

Depression is a common comorbidity among individuals with otolaryngologic disorders, particularly those with longstanding conditions. This study aims at analysing the sociodemographic profile of depressive disorders in patients with chronic otolaryngology symptoms or conditions, and the correlation with PHQ-9 score.

Methods

A cross-sectional study was conducted on a hundred patients presenting to the outpatient department with chronic otolaryngology symptoms or conditions. They were requested to fill in the PHQ-9 questionnaire, containing questions based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for major depressive disorder (MDD).

Results

Median age was 39, male: female ratio was 1.17. Nasal obstruction (29%), ear discharge (25%), and headache (17%) were the common presenting complaints. Mean and median PHQ-9 scores were 5.03 and 4 respectively. Seven patients (7%) had MDD, while eleven (11%) had other depressive disorder; 9% of cases were found to have no significant otolaryngologic problem despite presenting with symptoms, two of which were found to have depressive disorder. Thirty-five (35%) and thirty-six (36%) patients had minimal and mild depressive symptoms respectively, while one (1%) had severe depressive symptoms. Statistical significance was noted for the duration of symptoms (p-value 0.005); high statistical significance was found for occupation and otolaryngology diagnosis (p-value < 0.001 each). PHQ-9 score showed statistical significance in comparison with gender and duration of symptoms (p-value 0.046 and 0.005 respectively). Correlation of severity of depressive disorder revealed statistical significance with gender (p-value 0.049) and high statistical significance with duration of symptoms (p-value < 0.001).

Conclusion

Chronic otolaryngology conditions are associated with significant morbidity, attributable to longstanding disturbing symptoms and prolonged treatment protocols, leading to depression. Nevertheless, depression in chronic otolaryngology disorders may aggravate or overlap the clinical symptoms or may go undetected. Hence it may be worthwhile to evaluate for depressive disorders in chronic patients presenting to otolaryngology.
Characterization of exosome-mediated propagation of systemic inflammatory responses into the central nervous system
Authors: Kodali Mahesh Chandra , Salim Chinnu , Ismael Saifudeen , Lebovitz Sarah Grace , Lin Geng , Liao Francesca-Fang
Published: November 2024

The mechanisms through which systemic inflammation exerts its effect on the central nervous system (CNS) are still not completely understood. Exosomes are small (30 to 100 nm) membrane-bound extracellular vesicles released by most of the mammalian cells. Exosomes play a vital role in cell-to-cell communication. This includes regulation of inflammatory responses by shuttling mRNAs, miRNAs, and cytokines, both locally and systemically to the neighboring as well as distant cells to further modulate the transcriptional and/or translational states and affect the functional phenotype of those cells that have taken up these exosomes. The role of circulating blood exosomes leading to neuroinflammation during systemic inflammatory conditions was hereby characterized. Serum-derived exosomes from LPS-challenged mice (SDEL) were freshly isolated from the sera of the mice that were earlier treated with LPS and used to study the effects on neuroinflammation. Exosomes isolated from the sera of the mice injected with saline were used as a control. In-vitro studies showed that the SDEL upregulate pro-inflammatory cytokine gene expression in the murine cell lines of microglia (BV-2), astrocytes (C8-D1A), and cerebral microvascular endothelial cells (bEnd.3). To further study their effects in-vivo, SDEL were intravenously injected into normal adult mice. Elevated mRNA expression of pro-inflammatory cytokines was observed in the brains of SDEL recipient mice. Proteomic analysis of the SDEL confirmed the increased expression of inflammatory cytokines in them. Together, these results demonstrate and strengthen the novel role of peripheral circulating exosomes in causing neuroinflammation during systemic inflammatory conditions.
Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case–control study within the E3N-Generations cohort
Authors: Mercoeur Benoît , Fervers Béatrice , Coudon Thomas , Noh Hwayoung , Giampiccolo Camille , Grassot Lény , Faure Elodie , Couvidat Florian , Severi Gianluca , Mancini Francesca Romana , Roy Pascal , Praud Delphine , Amadou Amina
Published: November 2024

Background

Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk.

Methods

We used data from a nested case–control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects).

Results

The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00–5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13–4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93–4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05–1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75–1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol.

Conclusion

Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.
VI-VS: calibrated identification of feature dependencies in single-cell multiomics
Authors: Boyeau Pierre , Bates Stephen , Ergen Can , Jordan Michael I. , Yosef Nir
Published: November 2024

Unveiling functional relationships between various molecular cell phenotypes from data using machine learning models is a key promise of multiomics. Existing methods either use flexible but hard-to-interpret models or simpler, misspecified models.  (Variational Inference for Variable Selection) balances flexibility and interpretability to identify relevant feature relationships in multiomic data. It uses deep generative models to identify conditionally dependent features, with false discovery rate control. is available as an open-source Python package, providing a robust solution to identify features more likely representing genuine causal relationships.
Estimated diagnostic performance of prostate MRI performed with clinical suspicion of prostate cancer
Authors: Nakai Hirotsugu , Takahashi Hiroaki , LeGout Jordan D. , Kawashima Akira , Froemming Adam T. , Lomas Derek J. , Humphreys Mitchell R. , Dora Chandler , Takahashi Naoki
Published: November 2024

Purpose

To assess the diagnostic performance of prostate MRI by estimating the proportion of clinically significant prostate cancer (csPCa) in patients without prostate pathology.

Materials and methods

This three-center retrospective study included prostate MRI examinations performed for clinical suspicion of csPCa (Grade group ≥ 2) between 2018 and 2022. Examinations were divided into two groups: pathological diagnosis within 1 year after the MRI (post-MRI pathology) is present and absent. Risk prediction models were developed using the extracted eleven common predictive variables from the patients with post-MRI pathology. Then, the csPCa proportion in the patients without post-MRI pathology was estimated by applying the model. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV/NPV) of prostate MRI in diagnosing csPCa were subsequently calculated for patients with and without post-MRI prostate pathology (estimated statistics) with a positive threshold of PI-RADS ≥ 3.

Results

Of 12,191 examinations enrolled (mean age, 65.7 years ± 8.4 [standard deviation]), PI-RADS 1–2 was most frequently assigned (55.4%) with the lowest pathological confirmation rate of 14.0–18.2%. Post-MRI prostate pathology was found in 5670 (46.5%) examinations. The estimated csPCa proportions across facilities were 12.6–15.3%, 18.4–31.4%, 45.7–69.9%, and 75.4–88.3% in PI-RADS scores of 1–2, 3, 4, and 5, respectively. The estimated (observed) performance statistics were as follows: AUC, 0.78–0.81 (0.76–0.79); sensitivity, 76.6–77.3%; specificity, 67.5–78.6%; PPV, 49.8–66.6% (52.0–67.7%); and NPV, 84.4–87.2% (82.4–86.6%).

Conclusion

We proposed a method to estimate the probabilities harboring csPCa for patients who underwent prostate MRI examinations, which allows us to understand the PI-RADS diagnostic performance with several metrics.

Clinical relevance statement

The reported estimated performance metrics are expected to aid in understanding the true diagnostic value of PI-RADS in the entire prostate MRI population performed with clinical suspicion of prostate cancer.

Key Points

Calculating performance metrics only from patients who underwent prostate biopsy may be biased due to biopsy selection criteria, especially in PI-RADS 1–2.

The estimated area under the receiver operating characteristic curve of PI-RADS in the entire prostate MRI population ranged from 0.78 to 0.81 at three facilities.

The estimated statistics are expected to help us understand the true PI-RADS performance and serve as a reference for future studies.

Graphical Abstract
Peri-implant bone regeneration in pigs
Authors: Shanbhag Siddharth , Sanz-Esporrin Javier , Kampleitner Carina , Lie Stein-Atle , Gruber Reinhard , Mustafa Kamal , Sanz Mariano
Published: November 2024

Purpose

To review the current literature to answer the focused question: in the experimental pig model (population), which types of peri-implant bone defects (exposure) have been used evaluate different modes of therapy and what is their capacity for spontaneous healing and regeneration (outcome)?

Methods

Following PRISMA guidelines, electronic databases were searched for studies reporting peri-implant bone defects in the maxillae or mandibles of pigs. Those studies which reported a control group of untreated defects with assessment of spontaneous regeneration [new bone area (BA)] and/or re-osseointegration [new bone-to-implant contact (BIC)] via quantitative radiography or histomorphometry were included in a random effects meta-analysis for the outcomes BA and BIC.

Results

Overall, 21 studies, mostly performed in the mandibles of minipigs, were included. Most studies reported ‘acute’ intrabony (circumferential and/or dehiscence; n = 12) or supra-alveolar defects (horizontal; n = 4). Five studies attempted to induce ‘chronic’ peri-implantitis lesions using ligatures with conflicting results. Meta-analyses revealed pooled estimates (with 95% confidence intervals) of 48.07% BIC (30.14–66%) and 64.31% BA (42.71–85.91%) in intrabony defects, and 52.09% BIC (41.83–62.35%) and 28.62% BA (12.97–44.28%) in supra-alveolar defects. Heterogeneity in the meta-analysis was high (I2 > 90%).

Conclusion

Current evidence for peri-implant bone regeneration in pigs is mainly based on acute intrabony defects, which demonstrate a high capacity for spontaneous regeneration and re-osseointegration. The evidence for chronic peri-implantitis is limited and does not clearly indicate a spontaneous progression of the disease in this animal model.
Corona crisis disruptions and consequences for demand for freight transport: A screening of the effects for the largest logistics service providers in Norway
Authors: Hovi Inger Beate , Pinchasik Daniel Ruben
Published: November 2024

The present article investigates corona crisis disruptions and consequences for freight transport demand, using shipment data from major logistic service providers in Norway, as well as interviews. We investigate how Covid-19 affected demand for freight transport and transport volumes in different segments, changes for parcel delivery, home-deliveries, which industries were most affected and discussed main issues for LSPs in maintaining robust transport chains. We find temporary reductions in B2B deliveries after the first Norwegian societal lockdown but large volume increases in B2C deliveries, which remained at higher levels and saw further waves of increases. Especially home deliveries and mailbox deliveries of parcels increased, particularly in relation with new infection waves. At an aggregate level, retail trade experienced by far the largest volume increases, followed by transport and storage. The latter can in part be due to increasing low-volume import (parcels) from abroad being attributed to e.g. warehouses or customs. At the other end of the scale, wholesale trade stands out with the largest tonnage decrease, followed by manufacturing.
Biogenic synthesis of silver nanoparticles from Hylocereus undatus peel waste: exploring EGFR inhibition for targeted therapy of cervical and breast carcinomas
Authors: Reddy Kushala , Salve Preeti
Published: November 2024

Background

Cancer is one of the leading causes of death worldwide, with breast and cervical cancers being the most common among women. Over 100,000 new cases of breast cancer and 510,000 new cases of cervical cancer are diagnosed annually. This study aimed to develop and evaluate an eco-friendly, low-cost method to synthesize silver nanoparticles using Hylocereus undatus (dragon fruit) peel extract for their anticancer activity.

Results

Silver nanoparticles loaded with Hylocereus undatus fruit peel extract were successfully developed by a green synthesis technique and were optimized by UV–vis spectroscopy. The nanoparticles had an average size of 71.66 nm, a polydispersity index of 0.3754, and a zeta potential of − 38.52, with a spherical shape and 79.5% silver content. Their maximum absorbance was at 448 nm. Further, in vitro anticancer activity via MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay was evaluated and the synthesized nanoparticles displayed IC50 values at 23.51 µg/ml and 23.66 µg/ml against Hela and MDA MB 231 cell lines, respectively. Cytocompatibility studies showed high cell viability (≥ 95%) in L929 mouse fibroblast cells, indicating low toxicity. In silico analyses, including network pharmacology and molecular docking, identified kaempferol and quercetin as key anticancer compounds, with epidermal growth factor receptor (EGFR) (PDB ID: IM17) being the most significant protein target. Docking studies performed by using the Glide module of Schrodinger’s software displayed that kaempferol and quercetin had higher binding affinities for EGFR as compared to the standard drug erlotinib, with MET 769 being a crucial binding site.

Conclusion

Thus, the outcomes suggest that synthesized silver nanoparticles loaded with Hylocereus undatus fruit peel extract could be a potential and promising drug carrier aiding in cancer treatment.
Evaluation of factors associated with the temporomandibular joint dysfunction in university students
Authors: Altın Fatma Nur , Aslan Telci Emine , Özden Fatih
Published: November 2024

Background

Temporomandibular joint dysfunction (TMD) is a multifactorial and complex problem. The underlying causes of the symptoms and related factors of TMD should be specifically identified. This study aimed to examine factors in the relationship between TMD severity and compare cases regarding TMD severity in university students.

Methods

The participants were evaluated with the Visual Analog Scale (VAS) for jaw and neck pain severity. TMD severity was assessed with the Fonseca Anamnestic Index (FAI), sleep quality with the Pittsburgh Sleep Quality Index (PSQI), oral habits with the Oral Behavior Checklist (OBC), and depression and anxiety status with the Hospital Anxiety and Depression Scale (HADS). In addition, mandibular movements were also evaluated.

Results

A total of 51 individuals (39 female, 12 male; mean age: 21.9 ± 3.8) were included in the study. There was a positive moderate correlation between FAI and OBC (r = 0.560, p < 0.01). PSQI (r = 0,373), VAS-jaw pain (r = 0,374, p < 0.05), VAS-neck pain (r = 0,437, p < 0.05) and HADS-D (r = 0,392, p < 0.05) were moderately associated with FAI. There was also a low correlation between FAI and HADS-A (r = 0.346, p < 0.05). A statistically significant predictive correlation was found between VAS-Neck pain and OBC with FAI (p < 0.05).

Conclusions

This study's results show that jaw and neck pain, sleep habits, oral habits, and anxiety-depression levels are associated with TMD severity. This association highlights the need to consider these factors in assessing and treating TMD.
Observed Glycemic and Psychosocial Benefits in the Prospective Bigfoot Unity Real World Study: A 6-Month Analysis
Authors: Tillman John B , Beck Roy W , Polonsky William H , Calhoun Peter , Mouse Thomas , Bailey Ryan , Jacoby Jeanne , Nandan Rakesh , Sheikh F Naureen , Malone James K
Published: November 2024

Context

The Bigfoot Unity Diabetes Management System integrates Abbott FreeStyle Libre 2 continuous glucose monitoring (CGM) data into a smart insulin pen cap and mobile app, enabling clinician-directed insulin dose recommendations and real-time alerts.

Objective

The objective was to analyze real-world 6-month glycemic control in a prospective study for individuals using the System for multiple daily insulin injections (MDI).

Methods

We conducted a 6-month analysis from the BURST study (NCT05088265) of individuals with type 1 or type 2 diabetes (T2D). Participants reported baseline demographics, adverse events, and other survey data electronically. Either at-home kit or electronic medical record glycated hemoglobin A1c (HbA1c) data were collected.

Results

Of 102 participants in the per protocol cohort, median age was 59 years, 87% had T2D, 42% used CGM previously, 62% were White non-Hispanic, and 59% female. Mean HbA1c decreased from 9.1 ± 1.7% at baseline to 8.0 ± 1.2% at 6 months (mean difference −1.1%, 95% CI −1.4 to −0.8, P < .001). At 6 months, time in range (70-180 mg/dL), time at < 70 mg/dL, and time at < 54 mg/dL were 56 ± 23%, 1.0 ± 1.4%, and 0.04 ± 0.14%, respectively. Six severe hypoglycemia events occurred in 4 participants (none System-related) and no diabetic ketoacidosis events occurred in the per protocol cohort.

Conclusion

In this study primarily of older adults with T2D using MDI, durable glycemic improvement occurred using the System at 6 months, with the frequency of hypoglycemia being substantially below established targets of < 4% and < 1% for time below 70 and 54 mg/dL, respectively.
Delineating the Psychiatric Morbidity Spectrum in Congenital Adrenal Hyperplasia: A Population-based Registry Study
Authors: Lind-Holst Marie , Hansen Dorte , Main Katharina Maria , Juul Anders , Andersen Marianne Skovsager , Dunø Morten , Rasmussen Åse Krogh , Jørgensen Niels , Gravholt Claus Højbjerg , Berglund Agnethe
Published: November 2024

Context

Clinical studies of psychiatric morbidity in patients with congenital adrenal hyperplasia (CAH) imply impaired mental health.

Objective

To delineate psychiatric morbidity in a national CAH cohort by using complete data on psychiatric diagnoses from all Danish hospitals between 1977 and 2018 and on all psychiatric medication prescribed between 1995 and 2018.

Design

A registry-based cohort study.

Setting

A uniform public health care system.

Patients and controls

Four hundred and forty-eight patients (females: n = 215) with CAH, of which 410 had 21-hydroxylase deficiency (21-OHD) (females: n = 255) and 44 527 were age- and sex-matched general population controls.

Main outcome measures

Diagnoses were analyzed by negative binomial regression yielding incidence rate ratios (IRR). Medication were analyzed by Cox regression yielding hazard ratios (HR).

Results

21-OHD was associated with an increased risk of any psychiatric diagnosis; females: IRR = 2.32 (CI, 1.48-3.64), males: IRR = 2.74 (CI, 1.31-5.71) as well as of medication related to psychiatric disorders; females: HR = 1.74 (CI, 1.42-2.13), males: HR = 1.74 (CI, 1.30-2.33). Both females and males with 21-OHD had a significantly increased risk of alcohol use, stress and adjustment disorders, and of suicidal behavior. For patients with more rare forms of CAH (n = 24), the risk of any psychiatric diagnosis was significantly increased for males, IRR = 12.85 (CI, 1.78-92.87), but not for females, IRR = 0.54 (CI, 0.10-3.00). The risk of being prescribed psychiatric medication was not increased for neither females, HR = 1.05 (CI, 0.39-2.84), nor males, HR = 0.72 (CI, 0.10-5.13), with rare forms of CAH.

Conclusion

21-OHD is associated with a significantly increased psychiatric morbidity. This study underlines a need for awareness of mental health in patients with 21-OHD.
Cognitive Function in Individuals with Chronic Hypoparathyroidism—A Prospective Observational Study
Authors: Tmava-Berisha Adelina , Fahrleitner-Pammer Astrid , Stross Tatjana , Geiger Simon , Geiger Christina , Fellendorf Frederike , Scherkl Mario , Finner Alexander , Holl Anna , Dalkner Nina , Reininghaus Eva , Amrein Karin
Published: November 2024

Objective

“Brain fog” is a frequently reported, distressing experience among individuals with chronic hypoparathyroidism, characterized by reduced concentration and reduced ability to perform day-to-day tasks. However, evidence linking chronic hypoparathyroidism to cognitive impairment is limited and inconsistent. This study aimed to explore cognitive function in these patients using a validated neurocognitive test battery, compare results with a matched healthy control group, and analyze the frequency of cognitive impairment based on normative data.

Methods

The participants’ cognitive performance was tested using a cognitive test battery, including the Trail Making Test A/B, the Color-Word Interference Test, and the California Verbal Learning Test. These tests were used to evaluate the cognitive domains of attention and processing speed, verbal learning and memory, and executive function. In total, 30 individuals with hypoparathyroidism and 30 healthy controls were included.

Results

Twenty-four patients were women (80.0%), with a median age of 44.5 ± 13.1 and a median disease duration of 8.7 years (±5.3). Individuals with chronic hypoparathyroidism showed poorer cognitive performance in attention and processing speed [F(1,57) = 8.65, P = .005*, η2 = 0.13] compared to healthy controls. A significantly higher percentage of patients had cognitive deficits in both attention and processing speed (56.7% vs 3.3%) and executive function (60.0% vs 16.7%).

Conclusion

This study provides evidence that cognitive dysfunction, particularly in attention and processing speed, is common in chronic hypoparathyroidism. Recognizing cognitive impairment in these patients is crucial, especially when discussing workability. Neuropsychological training as an adjunct therapy strategy may be beneficial in managing these cognitive deficits.
Abrupt-mediated control of ninjurins regulates Drosophila sessile haemocyte compartments
Authors: Kwon So Yeon , Chan Kimberly , Stofanko Martin , Chan Ka Hei , Badenhorst Paul
Published: November 2024

Macrophage-like cells called haemocytes are key effectors of Drosophila cellular innate immune function. Larval haemocytes exist either in circulation or localize to segmentally repeated sessile haemocyte compartments (SHCs). While numerous functions have been proposed for SHCs, the mechanisms directing haemocytes to them are unclear. Here, we have exploited the developmentally regulated dispersal of SHCs that occurs at pupariation to identify the Abrupt (Ab) transcription factor (TF) and ninjurin cell-adhesion molecules as regulators of haemocyte recruitment to SHCs. We show that larval haemocytes express ninjurins, which are required for targeting haemocytes to SHCs. However, at pupariation, ecdysteroid signalling stimulates Ab expression, which collaborates with TFs, including Blimp-1 and Hr3, to repress ninjurins and disperse haemocytes. We observe that experimental manipulations that antagonize ninjurin function in larval haemocytes cause premature SHC dispersal, while stabilization of ninjurins in haemocytes blocks developmentally regulated SHC remodelling and increases sensitivity to immune challenges. Cumulatively, our data indicate that control of ninjurin activity provides a common target through which diverse developmental, environmental and immune stimuli can be integrated to control haemocyte dispersal and immune function.
Three-dimensional anatomy and dorsoventral asymmetry of the mature Marchantia polymorpha meristem develops from a symmetrical gemma meristem
Authors: Spencer Victoria , Wallner Eva-Sophie , Jandrasits Katharina , Edelbacher Natalie , Mosiolek Magdalena , Dolan Liam
Published: November 2024

Meristems are three-dimensional (3D) generative structures that contain stem cells and produce new organs and tissues. Meristems develop in all land plants; however we know little about the spatial and temporal regulation of meristem structure in lineages such as bryophytes. Here, we describe the 3D meristem anatomy during the development of the liverwort Marchantia polymorpha. We show that the apical stem cell of the mature meristem is sub-apical, ventral, and in the outer cell layer. Mature meristem anatomy is therefore asymmetrical in the dorsoventral axis, which is reflected by the domain-specific protein localisation of Class III and Class IV Homeodomain-Leucine-Zippers (MpC3HDZ and MpC4HDZ), and by the promoter activity of MpYUCCA2. The dorsoventral asymmetry that defines the mature meristem is absent in the juvenile meristems of asexual propagules known as gemmae. We discovered that anatomical dorsoventral asymmetry of the meristem forms after 1 to 2 days of gemmaling growth, and is accompanied by expression of the dorsal identity reporter MpC3HDZ. We conclude that the gemma meristem has arrested development and undergoes anatomical rearrangement to develop the 3D meristem structure of the mature plant.
The small ARF-like 2 GTPase TITAN5 is linked with the dynamic regulation of IRON-REGULATED TRANSPORTER 1
Authors: Mohr Inga , Eutebach Monique , Knopf Marie C. , Schommen Naima , Gratz Regina , Angrand Kalina , Genders Lara , Brumbarova Tzvetina , Bauer Petra , Ivanov Rumen
Published: November 2024

Iron acquisition is crucial for plants. The abundance of IRON-REGULATED TRANSPORTER 1 (IRT1) is controlled through endomembrane trafficking, a process that requires small ARF-like GTPases. Only few components that are involved in the vesicular trafficking of specific cargo are known. Here, we report that the ARF-like GTPase TITAN5 (TTN5) interacts with the large cytoplasmic variable region and protein-regulatory platform of IRT1. Heterozygous ttn5-1 plants can display reduced root iron reductase activity. This activity is needed for iron uptake via IRT1. Fluorescent fusion proteins of TTN5 and IRT1 colocalize at locations where IRT1 sorting and cycling between the plasma membrane and the vacuole are coordinated. TTN5 can also interact with peripheral membrane proteins that are components of the IRT1 regulation machinery, like the trafficking factor SNX1, the C2 domain protein EHB1 and the SEC14-GOLD protein PATL2. Hence, the link between iron acquisition and vesicular trafficking involving a small GTPase of the ARF family opens up the possibility to study the involvement of TTN5 in nutritional cell biology and the endomembrane system.