bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognition in patients with mild autonomous cortisol secretion at baseline and post-adrenalectomy
Authors: Saini Jasmine , Nathani Rohit , Singh Sumitabh , Ebbehoj Andreas , Thangamuthu Karthik , Suresh Malavika , Zhang Catherine D , Nevin Sophia , Fell Vanessa , Atkinson Elizabeth J , Achenbach Sara J , Stricker Nikki H , Bancos Irina
Published: December 2024

Objectives

The impact of mild autonomous cortisol secretion (MACS) on cognition is incompletely characterized. We aimed to assess cognition in patients with MACS, identify factors associated with lower cognition, and determine the impact of adrenalectomy on cognition.

Methods

We conducted a cross-sectional study (4/2019 to 10/2022) and a longitudinal cohort study (10/2021 to 9/2023) of adults with MACS and referent subjects. Cognition was assessed with National Institute of Health Toolbox Cognition Battery and reported as standardized T scores (adjusted for age, sex, race/ethnicity, and education) for fluid, crystallized, and total composite cognition. Participants were assessed with urine steroid profiling (liquid chromatography-tandem mass spectrometry), frailty index, Beck’s Depression Inventory (BDI), and Short Form-36 (SF-36).

Results

A total of 84 patients (median age 57 years, 67% women) and 201 referent subjects (median age 63 years, 58% women) were included. Patients with MACS demonstrated lower mean (SD) total composite (50.9 [9.3] vs 55.4 [8.9], P < .001) and fluid composite T score (49.3 [10.6] vs 55.2 [10.2], P < .001), but not crystallized composite T score (52.3 [8.4] vs 54.0 [8.4], P = .130) when compared with referent subjects. Multivariable analysis adjusted for age, sex, BDI, SF-36, frailty index, total glucocorticoids, and androgens demonstrated that MACS status was associated with lower cognition. When cognition was reassessed in 37 patients post-adrenalectomy and 31 referent subjects, adjusted group differences of cognition change were similar except for a higher comparative increase in attention and executive functioning in patients with MACS.

Conclusion

Patients with MACS demonstrate lower cognition than referent subjects. Adrenalectomy for MACS had a minor positive impact on cognition.
Rethinking cancer evolution: from genetic mutations to complex information systems in tumor reversion
Authors: Tez Mesut
Published: December 2024

Cancer research has historically focused on the somatic mutation theory, viewing cancer as a consequence of genetic mutations. However, this perspective has limitations in explaining phenomena like tumor reversion and cancer heterogeneity. This paper introduces an alternative approach: viewing cancer as a complex information-processing system shaped by its microenvironment. By integrating historical data on tumor reversion and insights into evolutionary dynamics, I propose a reframing of cancer biology. This process-oriented perspective highlights the role of cellular plasticity and adaptive behaviors, offering new pathways for therapeutic development.
A cost-effective, high-throughput, highly accurate genotyping method for outbred populations
Authors: Chen Denghui , Chitre Apurva S , Nguyen Khai-Minh H , Cohen Katerina A , Peng Beverly F , Ziegler Kendra S , Okamoto Faith , Lin Bonnie , Johnson Benjamin B , Sanches Thiago M , Cheng Riyan , Polesskaya Oksana , Palmer Abraham A
Published: December 2024

Affordable sequencing and genotyping methods are essential for large-scale genome-wide association studies. While genotyping microarrays and reference panels for imputation are available for human subjects, nonhuman model systems often lack such options. Our lab previously demonstrated an efficient and cost-effective method to genotype heterogeneous stock rats using double-digest genotyping by sequencing. However, low-coverage whole-genome sequencing offers an alternative method that has several advantages. Here, we describe a cost-effective, high-throughput, high-accuracy genotyping method for N/NIH heterogeneous stock rats that can use a combination of sequencing data previously generated by double-digest genotyping by sequencing and more recently generated by low-coverage whole-genome sequencing data. Using double-digest genotyping-by-sequencing data from 5,745 heterogeneous stock rats (mean 0.21× coverage) and low-coverage whole-genome sequencing data from 8,760 heterogeneous stock rats (mean 0.27× coverage), we can impute 7.32 million biallelic single-nucleotide polymorphisms with a concordance rate > 99.76% compared to high-coverage (mean 33.26× coverage) whole-genome sequencing data for a subset of the same individuals. Our results demonstrate the feasibility of using sequencing data from double-digest genotyping by sequencing or low-coverage whole-genome sequencing for accurate genotyping and demonstrate techniques that may also be useful for other genetic studies in nonhuman subjects.
Asymptotic consistency of the WSINDy algorithm in the limit of continuum data
Authors: Messenger Daniel A , Bortz David M
Published: December 2024

In this work we study the asymptotic consistency of the weak-form sparse identification of nonlinear dynamics algorithm (WSINDy) in the identification of differential equations from noisy samples of solutions. We prove that the WSINDy estimator is unconditionally asymptotically consistent for a wide class of models that includes the Navier–Stokes, Kuramoto–Sivashinsky and Sine–Gordon equations. We thus provide a mathematically rigorous explanation for the observed robustness to noise of weak-form equation learning. Conversely, we also show that, in general, the WSINDy estimator is only conditionally asymptotically consistent, yielding discovery of spurious terms with probability one if the noise level exceeds a critical threshold $\sigma _{c}$. We provide explicit bounds on $\sigma _{c}$ in the case of Gaussian white noise and we explicitly characterize the spurious terms that arise in the case of trigonometric and/or polynomial libraries. Furthermore, we show that, if the data is suitably denoised (a simple moving average filter is sufficient), then asymptotic consistency is recovered for models with locally-Lipschitz, polynomial-growth nonlinearities. Our results reveal important aspects of weak-form equation learning, which may be used to improve future algorithms. We demonstrate our findings numerically using the Lorenz system, the cubic oscillator, a viscous Burgers-growth model and a Kuramoto–Sivashinsky-type high-order PDE.
Neurturin gene IVSI-663 polymorphism but not RET variants is associated with increased risk for breast cancer
Authors: Taşkan Tuba , Noori Farshad , Kurukahvecioğlu Osman , Karaman Niyazi , Gönenç Aymelek
Published: December 2024

Background

Gene polymorphisms of rearranged during transfection (RET) and its ligand neurturin (NRTN) are one of the focus of studies in the investigation of cancer pathogenesis, invasion, and metastasis. In this study, we aimed to examine the possible risk of breast cancer between RET G691S, L769L, S904S, and NRTN IVSI-663 polymorphisms and to evaluate serum NRTN, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase (MMP)-2, MMP-9, and focal adhesion kinase (FAK) levels.

Methods

The study consists of 110 breast cancer patients and 110 controls. Polymorphisms were detected by the polymerase chain reaction method from study groups whole blood.

Results

The NRTN IVSI-663 polymorphism in G allele has been found to be 1.54 fold increased the risk of breast cancer, however AA genotype has been found 0.43 fold decreased the risk of breast cancer (P < .05, P < .05, respectively). Study groups showed a similar profile for RET G691S, L769L, S904S allele frequencies and genotype distributions (P > .05). In the patient group, significant increase in serum NRTN and FAK levels and decrease in MMP-2 and MMP-9 levels were found (P < .05, P < .05, P < .05, P < .05, respectively).

Discussion

In summary that increased breast cancer risk with the G allele in NRTN gene IVSI-663 polymorphism, as well as the increased serum NRTN and FAK levels, will contribute to the diagnosis, prognosis and determination of new treatment strategies.
On α-state filters in state residuated lattices
Authors: Wu Supeng , Liang Xingliang , Yang Jiang
Published: December 2024

The purpose of this paper is to investigate $\alpha $-state filters in a state residuated lattice. First, the notion of $\alpha $-state filters in a state residuated lattice is introduced. It is proved that the set of all $\alpha $-state filters in a state residuated lattice forms a complete Heyting algebra. Furthermore, the concept of quasicomplemented state residuated lattices is presented. Some equivalent conditions are derived for quasicomplemented state residuated lattices. Finally, the hull-kernel topology on the set of all prime $\alpha $-state filters in a state residuated lattice is investigated. It is demonstrated that the set of all prime $\alpha $-state filters under the hull-kernel topology is a spectral space and some certain conditions are given for the space to be either a $T_{1}$-space or a Hausdorff space. In addition, some topological characterizations are summarized for a state residuated lattice to be quasicomplemented.
Le diagnostic et la prise en charge de la syphilis congénitale : ne laisser passer aucune occasion
Authors: Fanella Sergio , Bitnun Ari , Barton Michelle , Sauvé Laura
Published: December 2024

La syphilis congénitale peut provoquer un arrêt de grossesse et une morbidité importante chez les nouveau-nés. L’épidémie actuelle de syphilis congénitale au Canada (particulièrement dans l’Ouest canadien) est une urgence sanitaire évitable. Les taux font foi d’un manque de contrôle de la syphilis dans la communauté et d’un manque de ressources de santé publique pour éviter une propagation qui s’est amorcée avant la pandémie de COVID-19. Les facteurs de risque incluent l’absence de soins prénatals, l’utilisation de méthamphétamines et d’autres substances psychoactives et l’instabilité du logement. Le dépistage, le traitement et le suivi pendant la grossesse, y compris chez les partenaires, constituent la pierre angulaire de la prévention. Les cliniciens qui s’occupent de nouveau-nés ont besoin d’examiner les aspects du traitement de la mère, le risque de réinfection, les résultats de la sérologie appariée de la syphilis chez la mère et le nouveau-né, de même que l’évaluation clinique du nouveau-né. Une évaluation complète du risque orientera la prise en charge et le suivi efficaces des nouveau-nés exposés à la syphilis in utero.
Exosomes released from immature neurons regulate adult neural stem cell differentiation through microRNA-7a-5p
Authors: Sun Xiujian , Chen Yexiang , Zhang Ying , Cheng Tiantian , Peng Huisheng , Sun Yanting , Liu Jing-gen , Xu Chi
Published: December 2024

Exosomes in the hippocampal dentate gyrus (DG) are essential for modulating the cell signaling controlling the neural differentiation of hippocampal neural stem cells (NSCs), which may determine the level of hippocampal adult neurogenesis. In the present study, we found that exosomes secreted by immature neurons may promote the neuronal differentiation of mouse NSCs in vitro. By miRNA sequencing, we discovered that miR-7a-5p was significantly lower in exosomes from differentiated immature neurons than those from undifferentiated NSCs. By modulating the level of miR-7a-5p, the mimic and inhibitor of miR-7a-5p could either inhibit or promote the neuronal differentiation of NSCs, respectively. Moreover, we confirmed that miR-7a-5p affected neurogenesis by directly targeting Tcf12, a transcription factor responsible for the differentiation of NSCs. The siRNA of Tcf12 inhibited neuronal differentiation of NSCs, while overexpression of Tcf12 promoted NSC differentiation. Thus, we conclude that the miR-7a-5p content in neural exosomes is essential to the fate determination of adult hippocampal neurogenesis and that miR-7a-5p directly targets Tcf12 to regulate adult hippocampal neurogenesis.
Multilevel factors influence the use of a cardiovascular disease assessment tool embedded in the electronic health record in oncology care
Authors: Kepper Maura M , Gierbolini-Rivera Raúl D , Weaver Kathryn E , Foraker Randi E , Dressler Emily V , Nightingale Chandylen L , Aguilar Aylin A , Wiseman Kimberly D , Hanna Jenny , Throckmorton Alyssa D , Craddock Lee Simon
Published: December 2024

Digital health tools are positive for delivering evidence-based care. However, few studies have applied rigorous frameworks to understand their use in community settings. This study aimed to identify implementation determinants of the Automated Heart-Health Assessment (AH-HA) tool within outpatient oncology settings as part of a hybrid effectiveness-implementation trial. A mixed-methods approach informed by the Consolidated Framework for Implementation Research (CFIR) examined barriers and facilitators to AH-HA implementation in four NCI Community Oncology Research Program (NCORP) practices participating in the WF-1804CD AH-HA trial. Provider surveys were analyzed using descriptive statistics. Interviews with providers (n = 15) were coded using deductive (CFIR) and inductive codes by trained analysts. The CFIR rating tool was used to rate each quote for (i) valence, defined as a positive (+) or negative (−) influence, and (ii) strength, defined as a neutral (0), weak (1), or strong (2) influence on implementation. All providers considered discussing cardiovascular health with patients as important (61.5%, n = 8/13) or somewhat important (38.5%, n = 5/13). The tool was well-received by providers and was feasible to use in routine care among cancer survivors. Providers felt the tool was acceptable and usable, had a relative advantage over routine care, and had the potential to generate benefits for patients. Common reasons clinicians reported not using AH-HA were (i) insufficient time and (ii) the tool interfering with workflow. Systematically identifying implementation determinants from this study will guide the broader dissemination of the AH-HA tool across clinical settings and inform implementation strategies for future scale-up hybrid trials.
Perioperative management of patients with mediastinal mass syndrome
Authors: Hachenberg Thomas , Schilling Thomas , Kretzschmar Moritz
Published: December 2024

Purpose of the review

The mediastinal mass syndrome (MMS) can occur after induction of anesthesia, intraoperatively or even days after the surgical procedure. The focus of this review is on the management of pediatric and adult patients with a significant mediastinal mass.

Recent findings

The age distribution of patients with mediastinal lesions suggests a bimodal shape, with an increased incidence among children under 10 years old and adults aged 60–70 years old. The traditional approach to avoid general anesthesia and mechanical ventilation has been challenged recently. Induction of general anesthesia may be achieved by a titrated intravenous infusion of propofol, with the patient positioned in a semi-sitting position. Mechanical ventilation with a prolonged I:E ratio, low respiratory rate and rigid or flexible bronchoscopy to stent the obstructed airway can facilitate expiration of tidal volume. Continuous video bronchoscopy recordings of the compromised portion of the airway have shown that positive pressure ventilation and neuromuscular blockade can induce an increase in the mean airway patency score.

Meticulous planning, implementation of anesthetic management protocols and protocols for emergency situations are essential to guarantee patient safety with a mediastinal mass.
Patient-reported outcomes in randomized controlled trials evaluating BRAF inhibitors in patients with cutaneous melanoma: a systematic scoping review of quality of reporting and trial results
Authors: Al-Naesan Imad , Krepper Daniela , Sparano Francesco , Sztankay Monika , Efficace Fabio , Giesinger Johannes M.
Published: December 2024

The objective of this study was to provide an overview of the current practice of patient-reported outcome (PRO) assessments in trials investigating treatment with BRAF inhibitors in patients with advanced melanomas. In addition, we extracted information on symptomatic adverse events (AEs) reported by clinicians to inform future PRO measurement strategies. For our systematic scoping review, we investigated randomized controlled trials (RCTs) evaluating treatment with BRAF inhibitors that had a primary, secondary or exploratory PRO endpoint and were indexed on PubMed. Two independent reviewers extracted information on general RCT characteristics, clinical results (e.g. survival, treatment response and symptomatic AEs) and the PRO measurement and results. Quality of PRO reporting using the CONSORT-PRO checklist was also assessed. We identified nine RCTs meeting the inclusion criteria, in which PROs were secondary or exploratory endpoints. In all trials but one, PROs were measured with the generic EORTC QLQ-C30 questionnaire. The quality of PRO reporting showed substantial variation across the different types of information, with information on handling of missing data and on PRO hypotheses lacking most frequently. Our analysis identified 29 relevant symptomatic AEs that could be reported directly by patients. Our findings may inform the planning of the PRO component of future RCTs, in particular regarding what symptoms and AEs should be covered by PRO measures to provide a comprehensive assessment of treatment tolerability. Our results also indicate a need for improving the quality of PRO reporting, to maximize the impact of PRO findings in real-word practice.
Sensitivity and Specificity of Slit-Lamp Demodex Infestation Detection in Patients With Blepharitis
Authors: Eskenazi-Betech Ruth , Zatarain-Barrón Naomi C. , Graue-Hernandez Enrique O. , Ramirez-Miranda Arturo , Kahuam-López Nicolás , Navas Alejandro
Published: December 2024

Purpose:

To determine whether the sensitivity and specificity of detecting Demodex infestation using slit-lamp examination are comparable with those of light microscopy.

Methods:

We evaluated 22 eyelids of 22 patients with clinical signs and symptoms of blepharitis that suggested Demodex infestation. Two lashes with cylindrical dandruff were epilated from each lid and mounted on a glass slide. A coverslip was mounted on each slide, then placed on a strip of white paper, and examined on a slit lamp with a 90D lens attached. Number of mites per lash were documented. The slides were then examined under a light microscope. The same procedure was followed with a control group. Results were evaluated per lash and per patient.

Results:

Twenty-two patients were included, 11 were men, with an average age of 54.8 years. A total of 176 epilated lashes were examined. Mean total Demodex count per lash was 0.9 ± 1.3 mites by slit-lamp examination and 1.22 ± 1.73 by light microscopy. Corresponding values per patient were 7.3 ± 4.4 and 9.7 ± 7.18. Correlation between Demodex counts by slit lamp and light microscopy was mildly positive and statistically significant per patient (8 lashes, r= 0.69, P < 0.001). Analysis of positive/negative results yielded 43.2% with a positive result for slit lamp and 51.7% for light microscopy. The sensitivity of the slit-lamp examination for the presence of Demodex per patient was 96.6%, with a specificity of 90.9%; the positive predictive value was 91.6%, and the negative predictive value was 95.2%.

Conclusions:

Demodex infestation in patients with blepharitis and cylindrical dandruff can be confirmed using a slit lamp. This technique demonstrates diagnostic performance that is noninferior to that of light microscopy.
Meralgia Paresthetica: An Anatomical Review and Surgical Case Presentation Utilizing a Robotic Exoscope
Authors: Kurtzman Joey S. , Barnett Joshua , Feng Rui , Taub Peter J. , Margetis Konstantinos
Published: December 2024

Background:

Meralgia paresthetica (MP) is a neuropathic condition marked by pain, tingling, and numbness in the anterolateral thigh, primarily caused by compression of the lateral femoral cutaneous nerve (LFCN). Although compression often occurs beneath the inguinal ligament, anatomical variations can lead to different entrapment sites. Treatments range from conservative measures to surgical decompression, depending on symptom severity. This study provides an anatomical review of the LFCN and presents a unique case of MP where the LFCN was compressed by the sartorius fascia rather than the typical site beneath the inguinal ligament. The study also explores the use of the Synaptive Modus X robotic exoscope for surgical decompression.

Methods:

This article presents a case study of a man in his 40s with a 15-year history of chronic MP symptoms, where the LFCN was atypically compressed by the sartorius fascia. Surgical decompression was performed using the robotic exoscope, a device offering high-definition, 3-dimensional visualization.

Results:

At 13 weeks postoperatively, the patient experienced improvement in thigh sensation and no pain. He returned to baseline ambulation with no complications. The exoscope allowed precise identification of the LFCN’s anatomy and compression site, proving effective in enhancing surgical precision.

Conclusions:

This is the first report of primary LFCN decompression using the Synaptive Modus X exoscope. The device provides excellent visualization, ergonomic benefits, and educational advantages, making it a valuable alternative to traditional microscopes and loupes in nerve decompression and other microsurgical procedures. Further studies are needed to assess its cost-effectiveness and broader applications in plastic surgery.
Management of Synthol-induced Fibrosis
Authors: Nassar Aref , Osseis Michael , Sleilati Fadi , Nasr Marwan , Abou Zeid Samer
Published: December 2024

Site enhancement oils, such as synthol, are sometimes used by bodybuilders to artificially increase muscle size and shape. However, these injections can lead to severe complications, including fibrosis, infections, and impaired muscle function. We report the case of a 45-year-old male patient who presented with severe fibrosis and recurrent infections in the pectoral region following synthol injections. The patient experienced several episodes of infection in the left pectoral area, which were treated with antibiotics, resulting in indurated, erythematous skin. The patient underwent surgical removal of the fibrotic tissue under general anesthesia. This case highlights the severe complications associated with synthol injections and underscores the importance of a meticulous surgical approach to manage these complications. Excision of fibrotic tissue is essential for reducing the risk of reinfection and restoring a normal appearance while carefully weighing the extent of tissue removal to avoid unnecessary damage to healthy structures. Preparing for potential blood loss and balancing the extent of tissue removal with the need to preserve normal function and appearance are crucial for successful outcomes.
Age-dependent differences in FIB-4 predictions of fibrosis in patients with MASLD referred from primary care
Authors: Sung Shuen , Al-Karaghouli Mustafa , Tam Matthew , Wong Yu Jun , Jayakumar Saumya , Davyduke Tracy , Ma Mang , Abraldes Juan G.
Published: December 2024

Background:

Fibrosis 4 (FIB-4) is widely used to triage patients with metabolic dysfunction–associated steatotic liver disease. Given that age is part of FIB-4, higher scores may be expected in the elderly population. This led to the proposal of using a higher threshold of FIB-4 to triage patients aged ≥65. Our main objective is to evaluate how age modifies the association between the FIB-4 index and disease severity based on the vibration-controlled transient elastography (VCTE) “rule of 5s.”

Methods:

In this cross-sectional study, we prospectively analyzed data from a primary care referral pathway. We used liver stiffness measurement by VCTE as a reference standard for liver risk. We modeled with ordinal regression the exceedance probabilities of finding different liver stiffness measurement thresholds according to FIB-4, and how age modifies FIB-4 predictions.

Results:

Nine hundred eighty-five participants with complete data were used for modeling. Participants aged ≥65 had a higher prevalence of advanced liver disease estimated by VCTE and higher FIB-4 values than those <65 (85.9% vs. 20.2% for FIB-4 ≥1.3, and 46.5% vs. 6.5% for FIB-4 ≥2.0). In participants age ≥65, the negative predictive value for VCTE ≥10 kPa of FIB-4 <1.3 was 100% versus FIB-4 <2.0 was 83%. Age significantly modified FIB-4–based prediction of fibrosis, but predictions at a threshold of 1.3 or 2 were only minimally altered. For higher FIB-4 threshold (ie, 2.7), age strongly modified FIB-4 predictions of liver stiffness measurement.

Conclusions:

Age does not relevantly modify FIB-4 predictions when using the common threshold of 1.3. Our data suggest no rationale for increasing the FIB-4 threshold to 2 for undergoing further testing in patients aged ≥65. However, the meaning of a FIB-4 of 2.7 strongly changes with age. This cutoff for ages over 65 is not enough to define high-risk and would not warrant direct referral.
Gaps in Knowledge Relevant to the “ICNIRP Guidelines for Limiting Exposure to Time-Varying Electric, Magnetic and Electromagnetic Fields (100 kHz TO 300 GHz)”
Authors:   International Commission on Non-Ionizing Radiation Protection (ICNIRP)
Published: December 2024

In the last 30 y, observational as well as experimental studies have addressed possible health effects of exposure to radiofrequency electromagnetic fields (EMF) and investigated potential interaction mechanisms. The main goal of ICNIRP is to protect people and the environment from detrimental exposure to all forms of non-ionizing radiation (NIR), providing advice and guidance by developing and disseminating exposure guidelines based on the available scientific research on specific parts of the electromagnetic spectrum. During the development of International Commission on Non-Ionizing Radiation Protection’s (ICNIRP’s) 2020 radiofrequency EMF guidelines some gaps in the available data were identified. To encourage further research into knowledge gaps in research that would, if addressed, assist ICNIRP in further developing guidelines and setting revised recommendations on limiting exposure, data gaps that were identified during the development of the 2020 radiofrequency EMF guidelines, in conjunction with subsequent consideration of the literature, are described in this Statement. Note that this process and resultant recommendations were not intended to duplicate more traditional research agendas, whose focus is on extending knowledge in this area more generally but was tightly focused on identifying the highest data gap priorities for guidelines development more specifically. The result of this distinction is that the present data gap recommendations do not include some gaps in the literature that in principle could be relevant to radiofrequency EMF health, but which were excluded because either the link between exposure and endpoint, or the link between endpoint and health, was not supported sufficiently by the literature. The evaluation of these research areas identified the following data gaps: (1) Issues concerning relations between radiofrequency EMF exposure and heat-induced pain; (2) Clarification of the relation between whole-body exposure and core temperature rise from 100 kHz to 300 GHz, as a function of exposure duration and combined EMF exposures; (3) Adverse effect thresholds and thermal dosimetry for a range of ocular structures; (4) Pain thresholds for contact currents under a range of exposure scenarios, including associated dosimetry; and (5) A range of additional dosimetry studies to both support future research, and also to improve the application of radiofrequency EMF exposure restrictions in future guidelines.
Successful surgical management of symptomatic antenatally diagnosed congenital pulmonary airway malformation: A case report
Authors: Mansour Marah , Naksho Abdulmonem , Abboud Yazan , Saqa Bayan , Yousif Mayas Ali
Published: December 2024

Background:

Congenital pulmonary airway malformations (CPAM) are rare developmental malformations of the lung with a prevalence of only 0.81/10,000. The exact cellular mechanisms are not fully understood yet. CPAM is often diagnosed on prenatal ultrasound (90% sensitivity and 77% specificity), around the second gestational trimester.

Case presentation:

A 30-year-old female had a routine ultrasound in the 13th gestational week which revealed cystic changes in the fetal left lung, along with mild polyhydramnios. This was monitored for the term of the pregnancy which ended with cesarean delivery at 39th week. The delivered baby had respiratory distress, needed an incubator for 24 hours, and underwent an open left lower lobectomy before being discharged home without any complications on follow-up.

Discussion and Conclusion:

Routine obstetric ultrasound is important in detecting CPAM and should be followed up routinely throughout the pregnancy. Management of CPAM is debatable and varies from conservative to invasive approaches. This case report emphasizes the significance of early prenatal diagnosis and timely surgical treatment, especially in resource-limited settings, in improving patient outcomes, while also contributing to a better understanding of this rare congenital condition.
Head-to-Head Comparison of 68Ga-DOTATATE and 18F-FDG PET in EBV-Positive Nonkeratinizing Nasopharyngeal Carcinoma
Authors: Qi Mengfang , Zhou Ping , Huang Shuhui , Su Minggang , Peng Xingchen , Huang Rui
Published: December 2024

Purpose

The aim of this study was to compare the clinical application value of 68Ga-DOTATATE and 18F-FDG PET/CT in Epstein-Barr virus (EBV)–positive nonkeratinizing nasopharyngeal carcinoma.

Patients and Methods

Patients underwent 18F-FDG and 68Ga-DOTATATE PET scans. The lesion numbers, tracer parameters, and primary tumor volume derived from contrast-enhanced MRI, 18F-FDG, and 68Ga-DOTATATE PET were compared. The correlation between clinical characteristics and PET parameters as well as the predictive value of PET parameters were analyzed.

Results

The median maximum standard uptake values (SUVmax) of 18F-FDG and 68Ga-DOTATATE in all 26 primary tumors was 15.00 and 9.73, respectively (P = 0.001). 68Ga-DOTATATE PET was superior to 18F-FDG PET in detecting intracranial and skull base involvement. The primary tumor volume of 68Ga-DOTATATE with 35% SUVmax as the threshold had the highest consistency with that of contrast-enhanced MRI. 68Ga-DOTATATE and 18F-FDG PET/CT detected 103/108 (95.4%) and 101/108 (93.5%) regional lymph nodes metastases (P = 0.552), and the median SUVmax was 6.05 and 10.81, respectively (P < 0.001). Furthermore, 68Ga-DOTATATE PET/CT detected more distant metastases than 18F-FDG (89/92 [96.7%] vs 54/92 [58.7%], respectively, P < 0.001). The plasma EBV DNA was positively correlated with the total metabolic tumor volume, lesion glycolysis, somatostatin receptor–expressing tumor volume, and lesion somatostatin receptor expression (all P values <0.05). The PET parameters in the non–objective response rate group were higher than those in the objective response rate group (all P values >0.05).

Conclusions

68Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic EBV-positive nonkeratinizing nasopharyngeal carcinoma and delineating primary tumor boundary.
Congenital transmission of Chagas disease: The role of newborn therapy on the disease’s dynamics
Authors: Boukaabar Meriem , Oduro Bismark , Chataa Paul
Published: December 2024

Chagas disease, also known as American trypanosomiasis, is caused by a protozoan blood-borne pathogen called Trypanosoma cruzi. The World Health Organization (WHO) has classified Chagas as one of 21 neglected tropical diseases present in the world and estimates that 6-7 million people are currently infected with Chagas. Congenital transmission of Chagas disease contributes to a significant amount of new infections, especially in endemic areas where 22.5% of new infections are due to congenital transmission. In this paper, we investigate the impact of congenital transmission on the dynamics of Chagas disease through a mathematical model. Specifically, we examine how treatment and the efficacy of the therapy for newborns impact the progression and spread of Chagas disease.

The influence of newborn therapy on the dynamics of the model is thoroughly investigated, both theoretically and numerically. The results illustrate the importance of an effective treatment for newborns in reducing infected cases of the Chagas. We observed that if vector transmission can be controlled, then at least 41% of the newborns need to be treated to curb the disease, and varying the newborn treatment rate and its efficacy significantly shapes the disease’s spread. The finding further shows that the therapy given to newborns is not sufficient but necessary to curb the transmission of Chagas disease, and a comprehensive approach that includes vector and vertical transmission control strategy is essential for eradicating Chagas disease.
Seroprevalence of measles and varicella in healthcare workers in Chonburi province, Thailand between October 2022 and January 2023
Authors: Katanyutanon Apirat , Thanasopon Wichai , Sonthichai Chaninan , Angsuwatcharakorn Piyada , Chansaenroj Jira , Nakabut Ratchathorn , Naritpavalun Sarandhorn , Prasitsomsakul Yanathep , Surakhot Paranyu , Pompim Phuvich , Wanlapakorn Nasamon , Poovorawan Yong
Published: December 2024

Introduction

Health care workers (HCWs) face the risk of contracting and transmitting vaccine-preventable infectious diseases (VPDs). Therefore, it is crucial to evaluate the immune status of HCWs against certain VPDs, such as measles and varicella zoster virus (VZV). This study aimed to determine age-specific seropositivity rates of anti-measles and anti-VZV IgG in HCWs working in Chonburi province, Thailand, and to develop a measles and varicella vaccination policy for Thai HCWs.

Methods

A total of 266 HCWs in Chonburi Province, Thailand, were enrolled in this study between October 2022 and January 2023. Participants were divided into six age groups: 21-30, 31-40, 41-50, 51-60, 61-70, and >70 years. Anti-measles and anti-VZV IgG levels were evaluated using commercial ELISA kits (EUROIMMUN, Lübeck, Germany).

Results

The overall seropositivity rates for measles and varicella were 85.0% and 81.2%, respectively. The lowest seropositivity rates for both measles and varicella were found among the 21-30-year-old group. Furthermore, seropositivity rates increased with age, reaching 100% among people over the age of 60 years.

Conclusions

To prevent measles and VZV outbreaks in HCWs, it is crucial to implement catch-up measles and varicella vaccination programs, particularly among HCWs younger than 30 years of age.
Alexander Disease: Screening andin silicofunctional characterization of variants on candidate gene
Authors: Malakar Surajit , Das Tathagata , Yadav Vikrant , Sahu Anurag , Das Parimal
Published: December 2024

Background

Alexander disease is a rare neurological ailment caused by the degeneration of the white matter of the brain accompanied with the formation of Rosenthal fibers, a unique cytoplasmic inclusion within astrocytes (non-nerve tissue) in the brain. Till to date only heterozygousde novomutation in Glial Fibrillary Acidic Protein (GFAP) gene is found to be associated for the disease phenotype.

Methods and Result

the aim of our study was to determine the genetic basis of an Indian-origin juvenile AxD patient with pathological symptoms of macrocephaly and psychomotor delay followed by regression, spastic parapresis and feeding difficulty. The patient was screened for mutation in candidate gene for AxD by Whole Exome Sequencing and the detected variants were further reconfirmed by Sanger sequencing. The clonicopathological feature were investigated and two heterozygous missence variants (c.983T>C and c. 626G>A) were indentify in GFAP gene of the patient. Familial screenings of both of these variants were predicted to be pathogenic or damaging by variousin silicomethods and prediction tools.

Conclusion

This altered GFA protein get accumulated in cytoplasm of the astroglial cells, leading to formation of Rosenthal fibers, which impairs cell function. Future study, however, would be helpful to understand the functional mechanism of these variant in formation of Rosenthal fibers leading to AxD pathophysiology.
Attention-mediated genetic influences on psychotic symptomatology in adolescence
Authors: Chang Sarah E. , Hughes Dylan E. , Zhu Jinhan , Hyat Mahnoor , Salone Sullivan D. , Goodman Zachary T. , Roffman Joshua L. , Karcher Nicole R. , Hernandez Leanna M. , Forsyth Jennifer K. , Bearden Carrie E.
Published: December 2024

Attention problems are among the earliest precursors of schizophrenia (SCZ). Here we examine relationships between multi-trait polygenic scores (PGS), psychotic spectrum symptoms, and attention-related phenotypes in an adolescent cohort (ABCD; n=11,855, mean baseline age: 9.93). Across three biennial visits, greater attentional variability and altered functional connectivity were associated with severity of psychotic-like experiences (PLEs). In European ancestry youth, neuropsychiatric and cognitive PGS were associated with greater PLE severity and greater attentional variability; notably, the effect of multi-trait PGS on PLEs weakened over time. Attentional variability partially mediated relationships between multi-trait PGS and PLEs, explaining 4-16% of these associations. Lastly, multi-trait PGS parsed by developmental co-expression patterns were significantly associated with greater PLE severity, though effect sizes were larger for genome-wide PGS. Findings suggest that broad neurodevelopmental liability is implicated in pathophysiology of psychotic spectrum symptomatology in adolescence, and attentional variability may act as an intermediate between risk variants and symptom expression.
TCMM: A Unified Database for Traditional Chinese Medicine Modernization and Therapeutic Innovations
Authors: Ren Zhixiang , Ren Yiming , Li Zeting , Xu Huan
Published: December 2024

Mining the potential of traditional Chinese medicine (TCM) in treating modern diseases requires a profound understanding of its action mechanism and a comprehensive knowledge system that seamlessly bridges modern medical insights with traditional theories. However, existing databases for modernizing TCM are plagued by varying degrees of information loss, which impede the multidimensional dissection of pharmacological effects. To address this challenge, we introduce traditional Chinese medicine modernization (TCMM), the currently largest modernized TCM database that integrates pioneering intelligent pipelines. By aligning high-quality TCM and Western medicine data, TCMM boasts the most extensive TCM modernization knowledge, including 20 types of modernized TCM concepts such as prescription, ingredient, target and 46 biological relations among them, totaling 3,447,023 records. We demonstrate the efficacy and reliability of TCMM with two features, prescription generation and knowledge discovery, the outcomes show consistency with biological experimental results. A publicly available web interface is athttps://www.tcmm.net.cn/.
Mapping echocardiogram reports to a structured ontology: a task for statistical machine learning or large language models?
Authors: Subramaniam Suganya , Rizvi Sara , Ramesh Ramya , Sehgal Vibhor , Gurusamy Brinda , Arif Hikamtullah , Tran Jeffrey , Thamman Ritu , Anyanwu Emeka , Mastouri Ronald , Mackensen G. Burkhard , Arnaout Rima
Published: December 2024

Background

Big data has the potential to revolutionize echocardiography by enabling novel research and rigorous, scalable quality improvement. Text reports are a critical part of such analyses, and ontology is a key strategy for promoting interoperability of heterogeneous data through consistent tagging. Currently, echocardiogram reports include both structured and free text and vary across institutions, hampering attempts to mine text for useful insights. Natural language processing (NLP) can help and includes both non-deep learning and deep-learning (e.g., large language model, or LLM) based techniques. Challenges to date in using echo text with LLMs include small corpus size, domain-specific language, and high need for accuracy and clinical meaning in model results.

Methods

We tested whether we could map echocardiography text to a structured, three-level hierarchical ontology using NLP. We used two methods: statistical machine learning (EchoMap) and one-shot inference using the Generative Pre-trained Transformer (GPT) large language model. We tested against eight datasets from 24 different institutions and compared both methods against clinician-scored ground truth.

Results

Despite all adhering to clinical guidelines, there were notable differences by institution in what information was included in data dictionaries for structured reporting. EchoMap performed best in mapping test set sentences to the ontology, with validation accuracy of 98% for the first level of the ontology, 93% for the first and second level, and 79% for the first, second, and third levels. EchoMap retained good performance across external test datasets and displayed the ability to extrapolate to examples not initially included in training. EchoMap’s accuracy was comparable to one-shot GPT at the first level of the ontology and outperformed GPT at second and third levels.

Conclusions

We show that statistical machine learning can achieve good performance on text mapping tasks and may be especially useful for small, specialized text datasets. Furthermore, this work highlights the utility of a high-resolution, standardized cardiac ontology to harmonize reports across institutions.
Development and Validation of Prediction Models for Sentinel Lymph Node Status Indicating Postmastectomy Radiotherapy in Breast Cancer: a Population-Based Study of 18 185 Women
Authors: Svensson Miriam , Bendahl Pär-Ola , Alkner Sara , Hansson Emma , Rydén Lisa , Dihge Looket
Published: December 2024

Background

Postmastectomy radiotherapy (PMRT) impairs the outcome of immediate breast reconstruction (IBR) in patients with breast cancer, and the sentinel lymph node (SLN) status is crucial in evaluating the need for PMRT. This study aimed to develop models to preoperatively predict the risk for SLN metastasis indicating the need for PMRT.

Methods

Women diagnosed with clinically node-negative (cN0) T1-T2 breast cancer from January 2014 to December 2017 were identified within the Swedish National Quality Register for Breast Cancer. Nomograms for nodal prediction based on preoperatively accessible patient and tumor characteristics were developed using adaptive LASSO logistic regression. The prediction of ≥1 and >2 SLN macrometastases (macro-SLNMs) adheres to the current guidelines on use of PMRT and reflects the exclusion criteria in ongoing clinical trials aiming to de-escalate locoregional radiotherapy in patients with 1-2 macro-SLNMs, respectively. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC) and calibration plots.

Results

Overall, 18 185 women were grouped into training (n=13 656) and validation (n= 4529) cohorts. The well-calibrated nomograms predicting ≥1 and >2 macro-SLNMs displayed AUCs of 0.708 and 0.740, respectively, upon validation. By using the nomogram for ≥1 macro-SLNMs, the risk could be updated from the pre-test population prevalence 13% to the post-test range 2%-75%.

Conclusion

Nomograms based on routine patient and tumor characteristics could be used for prediction of SLN status that would indicate PMRT need and assist the decision-making on IBR for patients with cN0 breast cancer.
Beyond IQ: Executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome
Authors: Pollak Rebecca M , Sefik Esra , Aberizk Katrina , Duan Kuaikuai , Espana Roberto , Guest Ryan M , Goldman-Yassen Adam E , Goines Katrina , Novacek Derek M , Saulnier Celine A , Klaiman Cheryl , Pulver Stormi , Cubells Joseph F , Burrell T Lindsey , Shultz Sarah , Walker Elaine F , Murphy Melissa M , Mulle Jennifer G
Published: December 2024

Background

3q29 deletion syndrome (3q29del) is a rare (∼1:30,000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function deficits in 47% of individuals with 3q29del; however, the nuances of executive function in this population have not been described.

Methods

We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world executive functioning in a cohort of 32 individuals with 3q29del (62.50% male, mean age=14.50±8.26 years). High-resolution structural magnetic resonance imaging was performed on a subset of participants (n=24).

Results

We found global deficits in executive function; individuals with 3q29del scored significantly higher than the population mean on the BRIEF Global Executive Composite (GEC) and all subscales. 81.25% of study subjects (n=26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC T scores were significantly higher among 3q29del participants with a diagnosis of ADHD, and BRIEF GEC T scores were significantly associated with schizophrenia spectrum symptoms as measured by the SIPS. The BRIEF-2 ADHD Form accurately (sensitivity=86.70%) classified individuals with 3q29del based on ADHD diagnosis status, highlighting its potential use as a screener for ADHD in this population. BRIEF GEC T scores were significantly correlated with cerebellar white matter and subregional cerebellar cortex volumes.

Conclusions

Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify executive function as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.
An AI-Cyborg System for Adaptive Intelligent Modulation of Organoid Maturation
Authors: Liu Ren , Ren Zhaolin , Zhang Xinhe , Li Qiang , Wang Wenbo , Lin Zuwan , Lee Richard T. , Ding Jie , Li Na , Liu Jia
Published: December 2024

Recent advancements in flexible bioelectronics have enabled continuous, long-term stable interrogation and intervention of biological systems. However, effectively utilizing the interrogated data to modulate biological systems to achieve specific biomedical and biological goals remains a challenge. In this study, we introduce an AI-driven bioelectronics system that integrates tissue-like, flexible bioelectronics with cyber learning algorithms to create a long-term, real-time bidirectionalbioelectronic interface withoptimizedadaptive intelligentmodulation (BIO-AIM). When integrated with biological systems as an AI-cyborg system, BIO-AIM continuously adapts and optimizes stimulation parameters based on stable cell state mapping, allowing for real-time, closed-loop feedback through tissue-embedded flexible electrode arrays. Applied to human pluripotent stem cell-derived cardiac organoids, BIO-AIM identifies optimized stimulation conditions that accelerate functional maturation. The effectiveness of this approach is validated through enhanced extracellular spike waveforms, increased conduction velocity, and improved sarcomere organization, outperforming both fixed and no stimulation conditions.