bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a questionnaire to identify barriers to the implementation of the Clinical Practice Guidelines for lower limb amputees in a middle‐income country
Authors: Posada‐Borrero Ana‐Maria , Plata‐Contreras Jesús , Lugo‐Agudelo Luz Helena , Velásquez‐Correa Juan Carlos , Patiño‐Lugo Daniel F. , del Pilar Pastor‐Durango Maria , Aguirre‐Acevedo Daniel Camilo
Published: March 2024

Aim

To develop and validate a questionnaire to identify the perceived barriers in the implementation of the Clinical Practice Guidelines for the lower limb amputee (CPG‐AMP).

Study Design and Setting

The study consisted of two stages: first, the development of the questionnaire based on a meta‐review of the literature and interviews with patients and health providers (mixed‐methods research). Second, the evaluation of its psychometric properties was performed. Participants included health providers from hospitals and clinics, prosthetic workshops and academic institutions in Colombia.

Results

A total of 90 items were obtained from the literature review and interviews. The validation of a preliminary 66‐item questionnaire was performed with 545 participants. After the factorial analysis, a 25‐item questionnaire with four domains was developed. Internal consistency was adequate in all domains, with Cronbach's α values between 0.76 and 0.83. Test–retest reliability in 58 participants yielded intraclass correlation coefficients between 0.51 and 0.59.

Conclusions

A 25‐item questionnaire with four domains (health system, guideline, institutional and individual) was proposed to measure the perception of barriers to the CPG‐AMP. The conceptual framework and the questionnaire can be used to identify barriers of other CPGs and to help design strategies aimed at improving its implementation.
Sex differences in cognitive function trajectories and their determinants in older adults: Evidence from the Chinese longitudinal healthy longevity survey
Authors: Tu Lihui , Lv Xiaozhen , Yuan Changzheng , Chen Hui , Yu Xin , Wang Huali , Zhang Qinge
Published: March 2024

Objectives

To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories.

Methods

The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008–2018 cohort. Cognitive function was measured using the Chinese version of the Mini‐Mental State Examination (MMSE). Group‐based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 10 years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes.

Results

Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9 h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline.

Conclusions

The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low‐income and developing countries.
General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning
Authors: Moodie Joanna E. , Harris Sarah E. , Harris Mathew A. , Buchanan Colin R. , Davies Gail , Taylor Adele , Redmond Paul , Liewald David C. M. , Valdés Hernández Maria del C. , Shenkin Susan , Russ Tom C. , Muñoz Maniega Susana , Luciano Michelle , Corley Janie , Stolicyn Aleks , Shen Xueyi , Steele Douglas , Waiter Gordon , Sandu Anca‐Larisa , Bastin Mark E. , Wardlaw Joanna M. , McIntosh Andrew , Whalley Heather , Tucker‐Drob Elliot M. , Deary Ian J. , Cox Simon R.
Published: March 2024

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region‐to‐region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell‐signalling/modification and transcription factors. We validate these patterns out‐of‐sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta‐analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|β| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health‐related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.
Online ratings and narrative comments of American Head and Neck Society surgeons
Authors: Kim Joshua K. , Tawk Karen , Kim Jonathan M. , Shahbaz Hady , Lipton Joshua A. , Haidar Yarah M. , Tjoa Tjoson , Abouzari Mehdi
Published: March 2024

Background

We analyzed online rating scores and comments of head and neck surgeons to understand factors that contribute to higher ratings.

Methods

Numerical ratings and comments for American Head and Neck Society physicians were extracted from Healthgrades, Vitals, RateMDs, and Yelp, with narrative comments categorized based on content. Physician practice location, education, and residency training were also compiled.

Results

Patient ratings were significantly higher with supportive staff and affable physician demeanor but showed significant drops with longer wait times and difficulties scheduling appointments or follow‐ups. Physician education and postgraduate training did not significantly affect ratings.

Conclusion

Online ratings and comments correlated to modifiable factors in clinical practice and may be informative in understanding patient needs.
Comparison of the prognostic value of lymph node yield, lymph node ratio, and number of lymph node metastases in patients with oral squamous cell carcinoma
Authors: Struckmeier Ann‐Kristin , Buchbender Mayte , Lutz Rainer , Agaimy Abbas , Kesting Marco
Published: March 2024

Background

The aim of this study was to assess the prognostic significance of lymph node yield (LNY), lymph node ratio (LNR), and the number of lymph node metastases (LNMs) in patients affected by oral squamous cell carcinoma (OSCC).

Methods

The study included patients who underwent surgical treatment for primary OSCC. Receiver operating characteristic curves were generated to determine the optimal threshold values. Kaplan–Meier curves were employed, along with the log‐rank test, for the analysis of survival. To compare the performance in terms of model fit, we computed Akaike's information criterion (AIC).

Results

This study enrolled 429 patients. Prognostic thresholds were determined at 22 for LNY, 6.6% for LNR, and 3 for the number of LNMs. The log‐rank test revealed a significant improvement in both overall survival and progression‐free survival for patients with a LNR of ≤6.6% or a number of LNMs of ≤3 (p < 0.05). Interestingly, LNY did not demonstrate prognostic significance. The AIC analyses indicated that the number of LNMs is a superior prognostic indicator compared to LNY and LNR.

Conclusions

Incorporating LNR or the number of LNMs into the TNM classification has the potential to improve the prognostic value, as in other types of cancers. Particularly, the inclusion of the number of LNMs should be contemplated for future N staging.
Darolutamide does not interfere with OATP‐mediated uptake of docetaxel
Authors: Buck Stefan A. J. , Talebi Zahra , Drabison Thomas , Jin Yan , Gibson Alice A. , Hu Peng , de Bruijn Peter , de Ridder Corrina M. A. , Stuurman Debra , Hu Shuiying , van Weerden Wytske M. , Koolen Stijn L. W. , de Wit Ronald , Sparreboom Alex , Mathijssen Ron H. J. , Eisenmann Eric D.
Published: March 2024

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient‐derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3‐mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drug–drug interaction was identified.
Treatment of Mycoplasma genitalium infection in pregnancy: A systematic review of international guidelines
Authors: Drew Richard J. , Eogan Maeve
Published: March 2024

Background

Mycoplasma genitalium is an emerging pathogen, which has been linked to cervicitis, urethritis and pelvic inflammatory disease (PID). With the advent of multiplex polymerase chain reaction (PCR) panels for sexually transmitted infections, it is increasingly being identified in pregnant women.

Objectives

The aim was to review international guidelines, which had explicit recommendations for treatment of M. genitalium infection in pregnancy and breastfeeding.

Search Strategy

PubMed, EMBASE and Cochrane databases were reviewed with no age, species, language or date restrictions.

Selection Criteria

Studies were included if they had an explicit recommendation for treatment of M. genitalium in pregnancy. Studies were excluded if there was no recommendation in pregnancy, if they referred to other international guideline recommendations or were historical versions of guidelines.

Data Collection and Analysis

References were manually reviewed and 50 papers were selected for review. Only four guidelines were included in the final analysis and they were from Europe, UK, Australia and Aotearoa New Zealand.

Main Results

All studies recommended azithromycin as first‐line treatment, and advised against moxifloxacin use. The dosing schedule of azithromycin, varied between guidelines, as did the utility/safety of pristinamycin for macrolide resistant infections. Safety data was generally reassuring for azithromycin but inconsistent for pristinamycin.

Conclusions

Azithromycin is the first‐line treatment for macrolide susceptible or unknown resistance infections, but there is a lack of consistency regarding dosing of azithromycin or the utility/safety of pristinamycin for macrolide resistant infections in pregnancy/lactation.
Are international guideline recommendations for the management of placenta accreta spectrum applicable in low‐ and middle‐income countries?
Authors: Nieto‐Calvache Albaro Jose , Jauniaux Eric , Fox Karin A. , Maya Juliana , Stefanovic Vedran , Weizsäcker Katharina , van Beekhuizen Heleen , Adu‐Bredu Theophilus , Collins Sally , Siaulys Monica , Hussein Ahmed M. , Duvekot Johannes , Aryananda Rozi , Pajkrt Eva , Rijken Marcus J. ,   the International Society for PAS (IS‐PAS) LMIC Working Group
Published: March 2024

Objective

The aim of this study was to explore how obstetricians‐gynecologists in low‐ and middle‐income countries (LMICs) can apply current international clinical practice guidelines (CPGs) for the management of placenta accreta spectrum (PAS) in limited resource settings.

Methods

This was an observational, survey‐based study. Clinicians with expertise in managing patients with PAS in LMICs were contacted for their evaluation of the recommendations included in four PAS clinical practice guidelines.

Results

Out of the 158 clinicians contacted, we obtained responses from 65 (41.1%), representing 27 middle income countries (MICs). The results of this survey suggest that the care of PAS patients in middle income countries is very different from what is recommended by international CPGs. Participants in the survey identified that their practice was limited by insufficient availability of hospital infrastructure, low resources of local health systems and lack of trained multidisciplinary teams (MDTs) and this did not enable them to follow CPG recommendations. Two‐thirds of the participants surveyed describe the absence of centers of excellence in their country. In over half of the referral hospitals with expertise in managing PAS, there are no MDTs. One‐third of patients with intraoperative findings of PAS are managed by the team initially performing the surgery (without additional assistance).

Conclusion

The care of patients with PAS in middle income countries frequently deviates from established CPG recommendations largely due to limitations in local resources and infrastructure. New practical guidelines and training programs designed for low resource settings are needed.
Complementary effects of information systems strategic assets and enabling roles of information systems on innovation performance of banking organizations
Authors: Obeng Asare Yaw , Opoku Samuel King , Obeng Ama Pokuah , Afriyie Emmanuel Oppong
Published: March 2024

Banking organizations improve innovation performance by recognizing rare strategic assets and efficient use of information systems. This study explored the role of information systems in enhancing internal operational effectiveness and leveraging firm capabilities for strategic positions. Using a mixed‐method design, 11 participants in six banking organizations in Ghana were interviewed to gather data. The results indicate IT contribution, organizational learning, and IS‐related human are the most significant attributes that positively impact innovation performance. Corroborating qualitative and experimental results identified new products, improved operational processes, improved product functionalities, and innovation strategy as the key innovation performance factors. While the information systems strategic assets have minimal effect, the enabling role of information systems has a moderate impact on innovation performance. In contrast to either information systems strategic assets or the enabling role of information systems alone, the results show their complimentary effect on innovation performance is considerably higher.
Best linear and quadratic moments for spatial econometric models with an application to spatial interdependence patterns of employment growth in US counties
Authors: Jin Fei , Lee Lung‐fei , Yang Kai
Published: March 2024

We provide a novel analytic procedure to construct best linear and quadratic moments of the generalized method of moments estimation for a large class of cross‐sectional network and spatial econometric models. These moments generate an estimator that is asymptotically more efficient than the quasi‐maximum likelihood estimator when the disturbances follow a non‐normal and unknown distribution. We apply this procedure to a high‐order spatial autoregressive model with spatial errors, where the disturbances are heteroskedastic. Two normality tests of disturbances are developed. We apply the model to employment data in US counties, which demonstrates spatial interdependence patterns of regional employment growth.
Explainable artificial intelligence in the design of selective carbonic anhydrase I‐II inhibitors via molecular fingerprinting
Authors: Kırboğa Kevser Kübra , Işık Mesut
Published: March 2024

Inhibiting the enzymes carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) presents a potential avenue for addressing nervous system ailments such as glaucoma and Alzheimer's disease. Our study explored harnessing explainable artificial intelligence (XAI) to unveil the molecular traits inherent in CA I and CA II inhibitors. The PubChem molecular fingerprints of these inhibitors, sourced from the ChEMBL database, were subjected to detailed XAI analysis. The study encompassed training 10 regression models using IC50 values, and their efficacy was gauged using metrics including R2, RMSE, and time taken. The Decision Tree Regressor algorithm emerged as the optimal performer (R2: 0.93, RMSE: 0.43, time‐taken: 0.07). Furthermore, the PFI method unveiled key molecular features for CA I inhibitors, notably PubChemFP432 (C(O)N) and PubChemFP6978 (C(O)O). The SHAP analysis highlighted the significance of attributes like PubChemFP539 (C(O)NCC), PubChemFP601 (C(O)OCC), and PubChemFP432 (C(O)N) in CA I inhibitiotable n. Likewise, features for CA II inhibitors encompassed PubChemFP528(C(O)OCCN), PubChemFP791 (C(O)OCCC), PubChemFP696 (C(O)OCCCC), PubChemFP335 (C(O)NCCN), PubChemFP580 (C(O)NCCCN), and PubChemFP180 (C(O)NCCC), identified through SHAP analysis. The sulfonamide group (S), aromatic ring (A), and hydrogen bonding group (H) exert a substantial impact on CA I and CA II enzyme activities and IC50 values through the XAI approach. These insights into the CA I and CA II inhibitors are poised to guide future drug discovery efforts, serving as a beacon for innovative therapeutic interventions.
Establishment and methodological evaluation of a chemiluminescence assay for detection of anti‐envelope protein (E1, E2) antibodies in the serum of hepatitis C virus‐infected patients
Authors: Wang Ningning , Liu Qingqing , Che Feihu , Sun Qingyang , Wang Yue , Yang Chunli , Dai Yuzhu , Cheng Jun
Published: March 2024

Background

To establish a chemiluminescence method for detecting anti‐E1 and anti‐E2 antibodies in the serum of patients with hepatitis C virus (HCV) infection.

Methods

The microplate was coated with recombinant envelope proteins E1 and E2 by indirect method, respectively, and the kits for detecting anti‐E1 and anti‐E2 antibodies were prepared. The methodological indexes were evaluated.

Results

The methodological indexes of the kits were as follows: precision test (the variation coefficient of anti‐E1 antibody 6.71%–8.95% for within run and 9.91%–12.16% for between run, the variation coefficient of anti‐E2 antibody 6.06%–8.44% for within run and 10.77%–13.98% for between run, respectively). The blank limit and detection limit were 1.18 RLIR and 3.16 RLIR for the anti‐E1 antibody, and 1.26 RLIR and 3.32 RLIR for the anti‐E2 antibody, respectively. The correlation coefficients (r) of anti‐E1 and anti‐E2 were 0.9963 and 0.9828, the analysis and measurement ranges (AMR) were 1.66–41.28 RLIR and 1.55–19.46 RLIR, and the average recovery was 96.4% and 93.7%, respectively. The rheumatoid factor and other positive serum samples had no interference or cross‐reaction to the test, and the kits were stable within 15 months. The positive rates of anti‐E1 and anti‐E2 antibodies in 45 patients with HCV infection were 35.6% (16/45) and 44.4% (20/45), respectively.

Conclusions

The kits for detecting anti‐E1 and anti‐E2 meet the requirements of methodology, and can be used in screening diagnosis, disease monitoring, prognosis evaluation, disease mechanism, and epidemiological studies of HCV infection. The HCV envelope proteins E1 and E2 have an immune response in HCV‐infected patients.
Hippocampal neurodegeneration induces transient endogenous regeneration and long‐term exhaustion of the neurogenic niche
Authors: Dey Jhilik , Chandra Sreyashi , Gupta Jalaj , Tripathi Prem Prakash
Published: March 2024

The hippocampal dentate gyrus, responds to diverse pathological stimuli through neurogenesis. This phenomenon, observed following brain injury or neurodegeneration, is postulated to contribute to neuronal repair and functional recovery, thereby presenting an avenue for endogenous neuronal restoration. This study investigated the extent of regenerative response in hippocampal neurogenesis by leveraging the well‐established kainic acid‐induced status epilepticus model in vivo. In our study, we observed the activation and proliferation of neuronal progenitors or neural stem cell (NSC) and their subsequent migration to the injury sites following the seizure. At the injury sites, new neurons (Tuj1+BrdU+ and NeuN+BrdU+) have been generated indicating regenerative and reparative roles of the progenitor cells. We further detected whether this transient neurogenic burst, which might be a response towards an attempt to repair the brain, is associated with persistent long‐term exhaustion of the dentate progenitor cells and impairment of adult neurogenesis marked by downregulation of Ki67, HoPX, and Sox2 with BrdU+ cell in the later part of life. Our studies suggest that the adult brain has the constitutive endogenous regenerative potential for brain repair to restore the damaged neurons, meanwhile, in the long term, it accelerates the depletion of the finite NSC pool in the hippocampal neurogenic niche by changing its proliferative and neurogenic capacity. A thorough understanding of the impact of modulating adult neurogenesis will eventually be required to design novel therapeutics to stimulate or assist brain repair while simultaneously preventing the adverse effects of early robust neurogenesis on the proliferative potential of endogenous neuronal progenitors.
Experimental investigation on nontoxic solvents for separation of vanillic acid
Authors: Eshwar Dhanush Shylaja , Antony Fiona Mary , Kumar Anuj , Wasewar Kailas
Published: March 2024

BACKGROUND

Vanillic acid, an aromatic carboxylic acid and a derivative of vanillin, is used as an additive in consumer goods for its aroma. Previously, most vanillic acid was produced through a petrochemical route, but as a consequence of stringent environmental policies, it is now produced by the biotransformation of ferulic acid. Vanillic acid is also found in the wastewater streams of paper‐pulp industries and olive‐oil mills. So, recovering vanillic acid from fermentation broth, either during bioproduction or from a wastewater stream, while minimizing toxicity, is a difficult task. In order to reduce the toxicity substantially, bio‐based solvents such as sunflower, mustard and rice bran oils were employed as diluents along with tri‐n‐butyl phosphate (TBP) as extractant in order to recover vanillic acid by reactive extraction.

RESULTS

The extraction performance was elucidated using terms such as distribution ratio, extraction efficiency, loading ratio and equilibrium complexation constant for different extractant–diluent combinations. The highest extraction efficiency and distribution ratio for the different solvents were in the following order: TBP + sunflower‐oil (72.02%–92.47%; 2.57–12.29) > TBP + rice bran‐oil (65.56%–90.55%; 1.90–9.58) > TBP + mustard‐oil(64.03%–89.87%; 1.78–8.87). The theoretical number of stages was determined as 4 to achieve a targeted extraction efficiency of 90%; these predictions were borne out experimentally.

CONCLUSION

In this study, vanillic acid was recovered from the aqueous phase using tri‐n‐butyl phosphate in sustainable, environmentally friendly, bio‐based solvents such as rice bran oil, sunflower oil and mustard oil. © 2024 Society of Chemical Industry (SCI).
Biology of Callistethus plagiicollis (Coleoptera: Scarabaeoidea: Rutelinae) and comparative morphology of its larvae
Authors: Long Tingting , Jiang Rixin , Zhu Wenli , Long Jiankun , Chen Xiangsheng
Published: March 2024

Larvae of the beetle subfamily Rutelinae are poorly described in the literature. Notably, the morphology of the larvae of Callistethus plagiicollis Fairmaire has not previously been analyzed. Here, we report for the first time that these larvae feed on the tubers and roots of Gastrodia elata Blume, an important traditional Chinese herbal medicine, which causes a reduction in the yield and economic value of G. elata. We employed scanning electron microscopy and light microscopy to investigate the morphology and occurrence regularity of egg, larvae, pupae, and adult specimens of C. plagiicollis collected from the G. elata planting base in Guizhou Province, China, with a focus on the ultrastructure of mature larvae. The results revealed one generation of C. plagiicollis per year in the study area and three instar stages of larvae. Mature larvae were identified by the following characteristics: raster without palidia with a large number of hamate setae, antennal apex containing seven sensilla basiconica, larval haptomerum containing eight sensilla styloconica and four enlarged heli, and seven longitudinally arranged stridulatory teeth on the stipes of the maxilla. The combination of scanning electron and light microscopy effectively revealed the difference between membranous and sclerotized structures, ensuring accurate identification of C. plagiicollis larvae. By determining the feeding characteristics and occurrence regularity of C. plagiicollis, this study has implications for improved pest management in G. elata crops.

Research Highlights

We identified C. plagiicollis as a new pest of G. elata, a traditional Chinese medicine

Scanning electron and light microscopy were combined to analyze the morphology of the mature larvae of C. plagiicollis for the first time

We determined the feeding characteristics and occurrence regularity of C. plagiicollis, which can be used to develop effective pest management strategies
Ramsey numbers upon vertex deletion
Authors: Wigderson Yuval
Published: March 2024

Given a graph , its Ramsey number is the minimum so that every two‐coloring of contains a monochromatic copy of . It was conjectured by Conlon, Fox, and Sudakov that if one deletes a single vertex from , the Ramsey number can change by at most a constant factor. We disprove this conjecture, exhibiting an infinite family of graphs such that deleting a single vertex from each decreases the Ramsey number by a super‐constant factor. One consequence of this result is the following. There exists a family of graphs so that in any Ramsey coloring for (i.e., a coloring of a clique on vertices with no monochromatic copy of ), one of the color classes has density .
Unlocking the potential of synthetic patients for accelerating clinical trials: Results of the first GIMEMA experience on acute myeloid leukemia patients
Authors: Piciocchi Alfonso , Cipriani Marta , Messina Monica , Marconi Giovanni , Arena Valentina , Soddu Stefano , Crea Enrico , Feraco Maria Valeria , Ferrante Marco , La Sala Edoardo , Fazi Paola , Buccisano Francesco , Voso Maria Teresa , Martinelli Giovanni , Venditti Adriano , Vignetti Marco
Published: March 2024

Artificial Intelligence has the potential to reshape the landscape of clinical trials through innovative applications, with a notable advancement being the emergence of synthetic patient generation. This process involves simulating cohorts of virtual patients that can either replace or supplement real individuals within trial settings. By leveraging synthetic patients, it becomes possible to eliminate the need for obtaining patient consent and creating control groups that mimic patients in active treatment arms. This method not only streamlines trial processes, reducing time and costs but also fortifies the protection of sensitive participant data. Furthermore, integrating synthetic patients amplifies trial efficiency by expanding the sample size. These straightforward and cost‐effective methods also enable the development of personalized subject‐specific models, enabling predictions of patient responses to interventions. Synthetic data holds great promise for generating real‐world evidence in clinical trials while upholding rigorous confidentiality standards throughout the process. Therefore, this study aims to demonstrate the applicability and performance of these methods in the context of onco‐hematological research, breaking through the theoretical and practical barriers associated with the implementation of artificial intelligence in medical trials.
Structure of the oral tentacles of early ontogeny stage in brachiopod Hemithiris psittacea (Rhynchonelliformea, Rhynchonellida)
Authors: Kuzmina Tatyana Valerievna , Temereva Elena Nikolaevna
Published: March 2024

Brachiopods have the most complex lophophore in comparison with other lophophorates, i.e., phoronids and bryozoans. However, at early ontogenetic stages, brachiopods have a lophophore of simple morphology, which consists of the oral tentacles. Data on the ultrastructure of the oral tentacles is mostly missing. Nonetheless, it has recently been suggested that the structure of oral tentacles is ancestral for all lophophorates in general, and for brachiopods in particular. The fine structure of the oral tentacles in the brachiopod Hemithiris psittacea is studied using light microscopy, transmission and scanning electron microscopy, cytochemistry and confocal laser scanning microscopy. The oral tentacles have a round shape in transverse section, and four ciliary zones, i.e., one frontal, two lateral, and one abfrontal. Latero‐frontal sensory cells occur among the frontal epithelium. Four basiepithelial nerves in the ciliary epithelium are colocalized with ciliary zones. Lophophores of simple morphology in phoronids and brachiopods are characterized by non‐specified round forms of tentacles. In phoronids and bryozoans, tentacles have additional latero‐frontal ciliary zones that function as a sieve during filtration. In most brachiopods, lateral cilia are involved in the capture of food particles, whereas latero‐frontal cells are retained in the frontal zone as sensory elements. The oral tentacles of H. psittacea contain a coelomic canal and have distinct frontal and abfrontal longitudinal muscles, which are separated from each other by peritoneal cells. A similar structure of tentacle muscles occurs in all bryozoans, whereas in phoronids, the frontal and abfrontal tentacle muscles are not separated by peritoneal cells. We suggest that the lophophorates' ancestor had tentacles, which were similar to the tentacles of some phoronids with lophophore of simple morphology. We also assume that the structure of the oral tentacles is ancestral for all brachiopods and the specialization of brachiopod tentacles correlates with the appearance of the double row of tentacles.
Evaluation of 4D Flow MRI‐Derived Relative Residence Time as a Marker for Cirrhosis Associated Portal Vein Thrombosis
Authors: Hyodo Ryota , Takehara Yasuo , Ishizu Yoji , Nishida Kazuki , Mizuno Takashi , Ichikawa Kazushige , Horiguchi Ryota , Kurata Nobuhiko , Ogura Yasuhiro , Yokoyama Shinya , Naganawa Shinji , Jin Ning , Ichiba Yoshito
Published: March 2024

Background

Portal vein thrombosis (PVT) is thought to arise from stagnant blood flow, yet conclusive evidence is lacking. Relative residence time (RRT) assessed using 4D Flow MRI may offer insight into portal flow stagnation.

Purpose

To explore the relationship between RRT values and the presence of PVT in cirrhotic participants.

Study Type

Prospective.

Population

Forty‐eight participants with liver cirrhosis (27 males, median age 67 years [IQR: 57–73]) and 20 healthy control participants (12 males, median age 45 years [IQR: 40–54]).

Field Strength/Sequence

3 T/4D Flow MRI.

Assessment

Laboratory (liver and kidney function test results and platelet count) and clinical data (presence of tumors and other imaging findings), and portal hemodynamics derived from 4D Flow MRI (spatiotemporally averaged RRT [RRT‐mean], flow velocity, and flow rate) were analyzed.

Statistical Tests

We used multivariable logistic regression, adjusted by selected covariates through the Lasso method, to explore whether RRT‐mean is an independent risk factor for PVT. The area under the ROC curve (AUC) was also calculated to assess the model's discriminative ability. P < 0.05 indicated statistical significance.

Results

The liver cirrhosis group consisted of 16 participants with PVT and 32 without PVT. Higher RRT‐mean values (odds ratio [OR] 11.4 [95% CI: 2.19, 118]) and lower platelet count (OR 0.98 per 1000 μL [95% CI: 0.96, 0.99]) were independent risk factors for PVT. The incorporation of RRT‐mean (AUC, 0.77) alongside platelet count (AUC, 0.75) resulted in an AUC of 0.84. When including healthy control participants, RRT‐mean had an adjusted OR of 12.4 and the AUC of the combined model (RRT‐mean and platelet count) was 0.90.

Data Conclusion

Prolonged RRT values and low platelet count were significantly associated with the presence of PVT in cirrhotic participants. RRT values derived from 4D Flow MRI may have potential clinical relevance in the management of PVT.

Evidence Level

2

Technical Efficacy

Stage 2
An energy‐efficient tunable threshold spiking neuron with excitatory and inhibitory function
Authors: Khanday Mudasir A. , Khanday Farooq A.
Published: March 2024

In this work, a complementary metal‐oxide‐semiconductor (CMOS) based leaky‐integrate and fire neuron has been proposed and investigated for neuromorphic applications. The neuron has been designed in Cadence Virtuoso and validated experimentally. It has been observed that the neuron consumes a maximum energy of 68.87 fJ/spike. The response of the neuron to excitatory as well as inhibitory inputs has been studied. To verify the applicability, the proposed neuron has been explored for reconfigurable threshold logic to implement various linearly separable Boolean functions including OR, AND, NOT, NOR, and NAND. Moreover, the threshold tunability of the neuron has also been verified and this property has been exploited to design threshold‐controlled logic gates. Instead of adjusting the weights of the applied inputs, the functionality of such gates can be controlled by changing the threshold of the neuron, simplifying the synaptic architecture of a neural network. Finally, a multilayer network has been designed and the recognition ability of the proposed network for MNIST handwritten digits has been verified with an accuracy of 96.93%.
Functional neuroanatomy of basal forebrain projections to the basolateral amygdala: Transmitters, receptors, and neuronal subpopulations
Authors: McDonald Alexander Joseph
Published: March 2024

The projections of the basal forebrain (BF) to the hippocampus and neocortex have been extensively studied and shown to be important for higher cognitive functions, including attention, learning, and memory. Much less is known about the BF projections to the basolateral nuclear complex of the amygdala (BNC), although the cholinergic innervation of this region by the BF is actually far more robust than that of cortical areas. This review will focus on light and electron microscopic tract‐tracing and immunohistochemical (IHC) studies, many of which were published in the last decade, that have analyzed the relationship of BF inputs and their receptors to specific neuronal subtypes in the BNC in order to better understand the anatomical substrates of BF‐BNC circuitry. The results indicate that BF inputs to the BNC mainly target the basolateral nucleus of the BNC (BL) and arise from cholinergic, GABAergic, and perhaps glutamatergic BF neurons. Cholinergic inputs mainly target dendrites and spines of pyramidal neurons (PNs) that express muscarinic receptors (MRs). MRs are also expressed by cholinergic axons, as well as cortical and thalamic axons that synapse with PN dendrites and spines. BF GABAergic axons to the BL also express MRs and mainly target BL interneurons that contain parvalbumin. It is suggested that BF‐BL circuitry could be very important for generating rhythmic oscillations known to be critical for emotional learning. BF cholinergic inputs to the BNC might also contribute to memory formation by activating M1 receptors located on PN dendritic shafts and spines that also express NMDA receptors.
False springs and spring phenology: Propagating effects of downscaling technique and training data
Authors: Wootten Adrienne M. , Dixon Keith W. , Adams‐Smith Dennis J. , McPherson Renee A.
Published: March 2024

Projected changes to spring phenological indicators (such as first leaf and first bloom) are of importance to assessing the impacts of climate change on ecosystems and species. The risk of false springs (when a killing freeze occurs after plants of interest bloom), which can cause ecological and economic damage, is also projected to change across much of the United States. Given the coarse nature of global climate models, downscaled climate projections have commonly been used to assess local changes in spring phenological indices. Few studies that examine the influence of the sources of uncertainty sources in the downscaling approach on projections of phenological changes. This study examines the influence of sources of uncertainty on projections of spring phenological indicators and false spring risk using the South Central United States. The downscaled climate projections were created using three statistical downscaling techniques applied with three gridded observation datasets as training data and three global climate models. This study finds that projections of spring phenological indicators and false spring risk are primarily sensitive to the choice of global climate models. However, this study also finds that the formulation of the downscaling approach can cause errors representing the daily low‐temperature distribution, which can cause errors in false spring risk by failing to capture the timing between the last spring freeze and the first bloom. One should carefully consider the downscaling approach used when using downscaled climate projections to assess changes to spring phenology and false spring risk.
Torsion constants and virtual mechanical tests are valid image‐based surrogate measures of ovine fracture healing
Authors: Ren Tianyi , Inglis Brendan , Darwiche Salim , Dailey Hannah L.
Published: March 2024

In large animal studies, the mechanical reintegration of the bone fragments is measured using postmortem physical testing, but these assessments can only be performed once, after sacrifice. Image‐based virtual mechanical testing is an attractive alternative because it could be used to monitor healing longitudinally. However, the procedures and software required to perform finite element analysis (FEA) on subject‐specific models for virtual mechanical testing can be time consuming and costly. Accordingly, the goal of this study was to determine whether a simpler image‐based geometric measure—the torsion constant, sometimes known as polar moment of inertia—can be reliably used as a surrogate measure of bone healing in large animals. To achieve this, postmortem biomechanical testing and microCT scans were analyzed for a total of 33 operated and 20 intact ovine tibiae. An image‐processing procedure to compute the attenuation‐weighted torsion constant from the microCT scans was developed in MATLAB and this code has been made freely available. Linear regression analysis was performed between the postmortem biomechanical data, the results of virtual mechanical testing using FEA, and the torsion constants measured from the scans. The results showed that virtual mechanical testing is the most reliable surrogate measure of postmortem torsional rigidity, having strong correlations and high absolute agreement. However, when FEA is not practical, the torsion constant is a viable alternative surrogate measure that is moderately correlated with postmortem torsional rigidity and can be readily calculated.
An interactive visualization and data portal tool (PALTIDE) for relative sea level and palaeotidal simulations of the northwest European shelf seas since the Last Glacial Maximum
Authors: Scourse James , Ward Sophie , Wainwright Adam , Bradley Sarah , Wilson Jerome Keaton , Guo Jessica
Published: March 2024

Relative sea level (RSL) predictions based on glacial isostatic adjustment (GIA) simulations and palaeotidal predictions generated by hydrodynamic models using GIA‐generated palaeotopographies are available in the published literature, and datasets are available via data repositories. However, these data are often difficult to extract for specific locations or timeslices, requiring users to request datasets from corresponding authors. To overcome the intractability of these data and to enable users to interrogate datasets themselves without requiring offline requests, we have developed PALTIDE, an online visualization tool with intuitive user interface accessible at https://shiny.bangor.ac.uk/paleotidal/. The model domain for this interactive visualization tool is the northwest European continental shelf, covering the period from the Last Glacial Maximum (LGM) to the present day, and is based on previous GIA simulations by Bradley and colleagues and hydrodynamic simulations using Regional Ocean Modelling System (ROMS) published by Ward and colleagues. The tool is developed in R and utilizes a number of packages including shiny and bslib for the frontend, and arrow, raster and the tidyverse for backend data processing. The tool enables visualizations and data downloads for RSL, tidal amplitude and tide‐dependent parameters for any location within the model domain over 1000‐year timesteps from the LGM to the present.
Donor age has no relevant role in biomechanical properties of allografts used in anterior cruciate ligament (ACL) reconstruction: A systematic review
Authors: Grassi Alberto , Agostinone Piero , Di Paolo Stefano , Altovino Emanuele , Gallese Alessandro , Akbaba Derya , Bonanzinga Tommaso , Marcacci Maurilio , Zaffagnini Stefano
Published: March 2024

Purpose

Surgeons generally consider the donor age as a factor that negatively influences the quality of allograft used in anterior cruciate ligament (ACL) reconstruction, however, the available evidence does not clearly support this statement. The purpose of the study was to investigate if donor age influences the biomechanical properties of allografts used in ACL reconstruction.

Methods

A comprehensive literature search was conducted for all relevant articles using MEDLINE (PubMed), Scopus, and Cochrane Collaboration Library, according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis. Studies including the analysis of the correlation between biomechanical properties of the allografts and donor age were selected. The role of donor age was labelled as ‘none’ if absent, ‘higher’ or ‘lower’ if the properties were higher or lower in older specimens with respect to younger. The correlation was defined as ‘weak’ or ‘strong’ according to each study definition.

Results

No conflicting role of donor age was reported for modulus of elasticity, load to failure, strain, stiffness and displacement. The only parameters where the significant results were consistent were the tensile strength and the stress (low or moderate correlations). When considering the tested samples with a donor's age <65 years, a significant role of age was reported in only four out of 13 groups of graft tested (patellar tendon, fascia lata, anterior tibialis tendon and posterior tibialis tendon).

Conclusion

The current literature did not allow to state that the donor age negatively influences the biomechanical properties of allografts, making it impossible to identify a clear age cut‐off value to exclude them from ACL reconstruction procedures.

Level of Evidence

Level IV, systematic review.
Alignment is only part of the equation: High variability in soft tissue distractibility in the varus knee undergoing primary TKA
Authors: Grosso Matthew J. , Wakelin Edgar A. , Plaskos Christopher , Lee Gwo‐Chin
Published: March 2024

Purpose

The purpose of this study is to evaluate the in vivo medial and lateral joint laxities across various total knee arthroplasty (TKA) alignment categories correlated to (1) hip–knee–ankle angle, (2) proximal tibial angle and (3) distal femoral angle in a consecutive group of patients undergoing robotic‐assisted TKA.

Methods

Using ligament tensions acquired during 805 robotic‐assisted TKA with a dynamic ligament tensor under a load of 70–90 N, the relationship between medial and lateral collateral ligament laxity and overall limb alignment was established. Only knees with neutral or mechanical varus alignment were included and divided into five groups: neutral (0°–3°), varus 3°–5°, varus 6°–9°, varus 10°–13° and varus ≥14°. Groups were further subdivided by the intraoperative medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA). The distraction of the medial and lateral sides was compared across the various alignments using an analysis of variance.

Results

The ability to distract the medial collateral ligament in extension and flexion was proportional to the degree of varus deformity, increasing from 4.0 ± 2.3 mm in the neutral group to 8.7 ± 3.2 mm in the varus ≥14° group (p < 0.0001). On the lateral side, the distraction of the lateral collateral ligament decreased in both extension (2.2 ± 2.4 vs. 1.2 ± 2.7, p < 0.0001) and flexion (2.8 ± 2.8 to 1.7 ± 3.0, p < 0.0001) with increasing native varus deformity. MPTA and LDFA had similar effects, where increasing MPTA varus and LDFA valgus increased medial distractibility in extension and flexion. There was significant variability of the stretch of the ligaments within and across all alignment categories, in which the standard deviation of the groups ranged from 2.0 to 3.0 mm.

Conclusion

This study demonstrates increased medial ligament distractibility with increasing varus deformity. However, there was significant variability in ligamentous laxity within various limb alignment categories suggesting the anatomy and soft tissue identity of the knee is complex and highly variable. TKAs seeking to be more anatomic will not only need to restore alignment but also native soft tissue tensions.

Level of Evidence

Level III, prognostic.