bluuebunny/crossref_metadata_2025 huggingface dataset:
Redes neurais convolucionais no diagnóstico de mielopatia cervical
Authors: Korkmaz Murat , Yılmaz Hakan , Korkmaz Merve Damla , Akgül Turgut
Published: December 2024

Objetivo As tecnologias de inteligência artificial são cada vez mais utilizadas em cirurgias de coluna como ferramentas diagnósticas. O objetivo do presente estudo foi avaliar a eficácia das redes neurais convolucionais no diagnóstico da mielopatia cervical (MC) em comparação à ressonância magnética (RM) cervical convencional.

Métodos O presente estudo foi transversal, descritivo e analítico. Cento e vinte e cinco participantes com diagnóstico clínico e radiológico de MC foram incluídos no estudo. Foram utilizadas imagens de RM sagital e axial em sequência ponderada em T2 da coluna cervical. Todas as imagens foram obtidas em 8 bits/pixel em duas categorias diferentes (MC e normal), tanto em vistas axiais quanto sagitais.

Resultados A validação transversal tripla evitou o sobreajuste (overfitting) durante o processo de treinamento. Duzentas e quarenta e duas imagens foram utilizadas para treinamento e teste do modelo criado para vistas axiais, que apresentou 97,44% de sensibilidade e 97,56% de especificidade. Duzentas e quarenta e nove imagens foram utilizadas para treinamento e teste do modelo criado para vistas sagitais, que apresentou 97,50% de sensibilidade e 97,67% de especificidade. Após o treinamento, a acurácia média foi de 96,7% (±1,53) para a vista axial e de 97,19% (±1,2) para a vista sagital.

Conclusão O deep learning (DL) apresentou grande melhora, especialmente na cirurgia de coluna. Observamos que a tecnologia de DL trabalha com maior acurácia do que em outros estudos na literatura para diagnóstico de MC.
Avaliação clínica comparativa de duas técnicas no tratamento artroscópico das lesões parciais articulares do manguito rotador após seis anos de seguimento
Authors: Sella Guilherme do Val , Silva Luciana Andrade da , Okamoto Ricardo Makoto , Marmille Hector Carmona , do Val Pedro Gabriel Pelegrino , Miyazaki Alberto Naoki
Published: December 2024

Objetivo Avaliar clinicamente a médio prazo os resultados do tratamento artroscópico das lesões parciais da porção articular do manguito rotador (LPPAMR) pelas técnicas de reparo transtendão (RTT) e reparo após completada a lesão (RPCL) utilizando-se a Escala Modificada de Avaliação do Ombro da University of California, Los Angeles (UCLA), a escala de Constant-Murley e análise de força.

Métodos Estudo retrospectivo de reavaliação, após seguimento mínimo de 6 anos, de casos de LPPAMR operados artroscopicamente, envolvendo um total de 34 pacientes, sendo 18 submetidos ao RTT e 16 ao RPCL. Foram comparadas as pontuações atuais nas escala da UCLA e de Constant-Murley, a força média entre as técnicas, e as pontuações na UCLA atualmente e com 2 anos de pós-operatório do mesmo grupo, conforme publicado em estudo anterior, a fim de avaliarmos se houve ou não modificação dos resultados ao longo do tempo.

Resultados Não houve diferença estatística entre as pontuações nas escalas. As pontuações na escala da UCLA atual foram de 33,8 para o RTT e de 32,9 para o RPCL (p = 0,113), e na escala de Constant-Murley, foram de 91,9 e 86,8, respectivamente (p = 0,075). Para o RTT, a pontuação anterior na escala da UCLA (com 2 anos de pós-operatório) foi 32,4, e a atual, de 33,8 (p = 0,374); para o RPCL, foi de 32,4 com 2 anos de pós-operatório, e de 32,9 atualmente (p = 0,859). No RTT, a força média foi estatisticamente maior do lado dominante (11 kg) do que no não dominante (7,80 kg) (p = 0,023) e aqueles do RPCL (8,25 kg) (p = 0,042).

Conclusão Não houve diferença estatística em médio prazo na comparação das pontuações nas escalas da UCLA e de Constant-Murley em relação à técnica utilizada (RTT ou RPCL), nem alteração nas pontuações na escala da UCLA entre 2 e 6 anos de pós-operatório. Nos pacientes submetidos à RTT, a força média foi estatisticamente maior do lado dominante do que no não dominante, e maior do que nos pacientes submetidos à RPCL.
Prótese de polipropileno no tratamento de lesões extensas e cobertura de áreas doadoras sem enxerto: Série de casos
Authors: Uchôa Raphael De Sá Vasconcelos , Ferreira Luís Filipe e Silva Lessa , Uchôa Ana Luiza Simões de Brito
Published: December 2024

Objetivo Avaliar a eficácia do uso das próteses de polipropileno no tratamento de ferimentos extensos nos membros.

Métodos Foram avaliados 13 pacientes quanto aos aspectos finais do tratamento, incluindo presença de epitelização e granulação, redução de área cruenta e cobertura de estruturas profundas.

Resultados Uma redução maior que 40% da área cruenta e cobertura completa de estruturas nobres foram visualizadas.

Conclusão Evidenciou-se uma alternativa eficaz, reprodutível e de baixo custo no tratamento de lesões extensas.
Diagnóstico das lesões meniscais em rampa
Authors: Jorge Pedro Baches , Oliveira Diego Escudeiro de , Mussatto Guilherme do Amaral , Horita Melanie Mayumi , Salas Victor Eduardo Roman , Jorge Rafael Baches
Published: December 2024

Objetivo: Comparar os métodos diagnósticos para lesão meniscal em rampa (ressonância magnética, artrotomografia e artroscopia) evidenciando qual o método mais sensível e qual o grau de concordância entre os métodos.

Método: Foram estudados 21 pacientes, sendo esses, jovens, atletas, com suspeita de lesão do LCA após trauma há pelo menos 3 meses, sem evidências ou histórico de outras lesoes osteoarticulares no joelho. Para isso os pacientes foram submetidos a ressonância magnética, artrotomografia e após a confirmação da lesão do LCA foi realizada artroscopia para reconstrução ligamentar e avaliação do menisco medial para confirmar ou excluir o diagnóstico de lesão em rampa. Os métodos diagnósticos foram comparados pelo teste de concordância de McNemar, sendo também avaliada especificidade e sensibilidade, utilizando como padrão ouro a artroscopia, com intervalo de confiança de 95% e p < 0,005.

Resultado: Os resultados foram semelhantes com os já encontrados na literatura. A ressonância magnética apresentou sensibilidade de 73,3% e especificidade de 83,3%, com uma concordância de 76,2% com o padrão ouro. Já a artrotomografia apresentou sensibilidade e especificidade de 100% e 66,7% respectivamente, com uma concordância de 90,5% com a artroscopia.

Conclusão: Neste trabalho, a artrotomografia se apresentou como o método diagnóstico mais sensível e com maior concordância com o padrão ouro, devendo ser considerada na investigação diagnóstica de pacientes com lesão do LCA.
Automated Assessment of Sarcopenia with Hounsfield Unit Average Calculation in Computed Tomography Scans Using Deep Learning Techniques
Authors: Rengan Vinayak , Meenashi Sundaram Pravin , Arora Eham , Ravanasamudram Sitaraman Rengan , Sekaran Praveen , Kalla Rohit , Bawa Ashvind , Alexander Naveen , Ramanan Rochita V.
Published: December 2024

Introduction Skeletal muscle is increasingly plastic with an ability to gain or lose tissue. Depletion of muscle mass and quality occurs due to various factors such as aging, disease, and disuse. Sarcopenia can be loosely defined as a significant loss of muscle mass and function. Sarcopenia is now recognized as an independent risk factor for various patient-related negative outcomes after various surgeries. Various computed tomography (CT) based imaging indices for assessment of sarcopenia exist in practice. The psoas muscle Hounsfield unit average calculation (HUAC) has been proven to be an effective one as it is independent of patient anthropometric data, and it can be calculated in the images provided.

Aim The aim of this study is to develop automated tools for estimation of the HUAC using deep learning algorithms.

Materials and Methods A total of 41 abdominal CTs were used. Ground truth was established and validated by two radiologists with more than 5 and 10 years of experience each. Models were trained to identify the psoas muscle among the slices and calculate the HUAC.

Results At inference, an average intersection over union (IoU) value of 90% was obtained between the deep learning model outputs and the original annotated test images for the CT slices. The Dice coefficient was 0.90 between the ground truth labels and the output from the model.

Conclusion We have demonstrated the accuracy of our deep learning–based algorithm for quantifying the psoas muscle HUAC, which is a marker for sarcopenia. There is a potential for a fully automated measure to calculate the HUAC for any patient undergoing CT scan.
High Success Rate in Sealing Distal Coronary Artery Perforations Using Absorbable Gelatin Sponge
Authors: Hashemi Arash , Serati Alireza , Ahmadieh Arsis , Ghaffari Lida , Movahed Mohammad R.
Published: December 2024

Coronary artery perforation (CAP) is a major complication of percutaneous coronary intervention (PCI). The management of CAP can be challenging, requiring tailored approaches based on specific clinical scenarios. We are reporting outcome data on six patients who experienced distal CAP during PCI and were 100% successfully treated using absorbable gelatin sponge embolization without procedural or immediate postprocedural complications.
Transverse susceptibility of a double Ising chain
Authors: Yurishchev M. A.
Published: December 2024

The initial static transverse susceptibility is calculated for a double Ising chain whose Hamiltonian is invariant relative to the simultaneous reflection of all spins. The possibility is also noted of finding the imaginary part of the transverse dynamic susceptibility that governs the form of the magnetic resonance spectrum.
Pseudopairwise potential and lattice dynamics of rare-gas crystals
Authors: Ratner A. M. , Shamfarova O. Ya.
Published: December 2024

We considered the potential U = Ur+ Uc of a system of rare-gas atoms, where Uc is the Van der Waals potential and Ur is the repulsion potential determined by the permutation symmetry of the many-electron wave function Ψ. Hartree-Fock calculations of Ur are cumbersome and unreliable. In view of this, in calculating Ur, we made allowance for the permutation symmetry in a different way, i.e., by using the nodal surface Σ, of the function Ψ generated by the symmetry. In some important particular cases the form of the surface Σ is found from general considerations. Thus, for a pair of rare-gas atoms A and B the surface Σ is close to a plane normal to the segment AB and dividing it in a ratio which does not depend on its length. For the wave function of an atom in a lattice Σ is a polyhedron formed by such planes. The many-particle repulsion potential, obtained as the difference of the energy of atoms with and without the nodal surface, is approximated (with an estimation of the error) by the sum of pair-wise potentials U(2) (Ref. 1). The potential U(2), which (unlike the true pairwise potential) depends on the lattice constant, is called pseudopairwise; it contains a parameter β which determines the position of the nodal surface. The other unknown parameter of the potential U = Ur + Uc is the coefficient C in the principal term of the expansion of the Van der Waals potential (determining the other terms as well2). The calculations for an anharmonic lattice described by a pseudopairwise potential were performed by a variational method with subsequent estimation and correction of the systematic error. With an optimal choice of β and C all the calculated functions (phonon dispersion law, specific heat, thermal expansion, and compressibility over a wide range of temperatures and pressures) for Ne, Ar, and Kr crystals practically coincide with experimental data. The values of β so determined, virtually the same for various rare-gas atoms, can also be used in calculations for closed-shell ions. The values of C somewhat exceed the data obtained by nonrelativistic calculations3 (the discrepancy increases with an increase in the atomic number). For comparision with the pseudopairwise potential, in much the same way we obtained the true pairwise (molecular) potential; the difference between them is governed by a law and amounts to several per cent.
On the theory of electron–ripplon resonances in a two-dimensional Wigner crystal on a liquid-helium surface
Authors: Monarkha Yu. P.
Published: December 2024

A theoretical study is made of the structure of resonance anomalies in the high-frequency conductivity of a two-dimensional electron crystal on the free surface of liquid helium in a uniform electric field parallel to the liquid-vapor interface. New mechanisms responsible for these resonances are suggested and analyzed. It is shown that in relatively weak driving fields (of the order of 1 mV/cm) nonlinear effects resulting in additional, low-frequency resonances are significant. Under nonresonance conditions we calculate the concentration and frequency dependence of the conductivity of the two-dimensional Wigner crystal; this can provide interesting information about the character of the dissipative processes near the free surface of liquid helium.
Dependence of differential (“flux-flow”) resistance on critical current with allowance for superheating of samples
Authors: Goncharov I. N. , Dorofeev G. L. , Pasyuk V. V. , Khukhareva I. S.
Published: December 2024

Current-voltage characteristics for cold-worked ribbon samples of Nb-(76–80%)Zr superconducting alloys were measured at various temperatures, various magnetic field intensities, and various orientations of the magnetic field relative to the plane of the sample. The critical current was varied through more than one order of magnitude. Current-voltage characteristics were then calculated for various angles between the magnetic field and the place of the sample, taking into account superheating of the sample at its center and assuming that differential resistance does not depend on critical current. The close agreement between calculated and measured current-voltage characteristics supports this assumption (where the maximum pinning force is 5 · 107 dyn/cm3 at T = 1.85 °K). The problem of the stability of the resistive state, which is related to heat transfer to the liquid helium, is considered.
Anisotropy of critical fields of columnar vanadium films
Authors: Sidorenko A. S. , Kolin’ko A. E. , Rybal’chenko L. F. , Cherkasova V. G. , Fogel’ N. Ya.
Published: December 2024

We studied the anisotropy of the critical magnetic fields of thin columnar vanadium films. The position of the secondary maximum on the Hc(Θ) curve changed according to the conditions under which the films were grown. It was found that impurities as well as the structure of the films were responsible for the anomalous behavior of Hc(Θ). The effect is discussed within the framework of a model in which the impurity concentration in the superconductor experiences periodic modulation due to the columnar structure of the specimens.
Peak effect due to vortex pinning in the subsurface layer of a type II superconductor
Authors: Ashimov S. M. , Batsankalashvili T. P. , Nedzelyak N. L. , Tsakadze Dzh. S.
Published: December 2024

Using a mechanical method, we study the strength of Abrikosov fluxoid pinning in niobium single crystals as a function of the external magnetic field. It is shown that this dependence displays maxima near Hc1 and Hc2 and that the first is due to the existence of a barrier in the subsurface layer of the superconductor which hinders vortices in entering and leaving the specimen.
Limitations in the microwave stimulation of superconductivity
Authors: Bevza G. , Dmitrenko I. M. , Karamushko V. I. , Turutanov O. G.
Published: December 2024

A limitation of the stimulation of superconductivity is observed in measurements of critical current as a function of the incident microwave power in narrow long films of tin, with a sudden fall of the critical current to zero at a certain critical radiation power. This limitation is due to the occurrence of a spatially nonuniform state, the existence of which in the film is confirmed by the form of the current-voltage characteristics. A numerical calculation carried out using Eliashberg’s theory, taking into account the heating due to the microwave field, does not agree with the thermal mechanism of the limitation of stimulation.
Anomalies of electronic sound absorption in rare-earth metals at the transition to the helical phase
Authors: Lobanova T. L.
Published: December 2024

We consider anomalies which appear in the electronic sound absorption coefficient Γe in rare-earth metals at the transition to the helical phase. The character of the Γe anomalies are shown to depend essentially on the topology of that segment of the Fermi phase which is responsible for the formation of the helical magnetic structure.
Toward a quantum theory of spin excitations in cobalt carbonate
Authors: Loktev V. M. , Ostrovskii V. S.
Published: December 2024

Using a self-consistent quantum calculation, expressions are obtained for the energies of spin excitations of CoCO3, and the energy parameters of the crystal are evaluated.
High frequency properties of antiferroelectric ferrites
Authors: Chupis I. E.
Published: December 2024

Expressions are obtained for the spectrum of coupled magnetoelectric oscillations and the high frequency susceptibility tensor in a uniaxial antiferroelectric ferrite. It is shown that electrical polarization oscillations may cause the appearance of an extremum in the temperature dependence of the magnetization below the electric and magnetic transition temperatures. The possibility of spin wave participation in the detection of an ac electric field is demonstrated.
Linear magnetic birefringence of light in ferromagnetic materials
Authors: Genkin G. M. , Golubeva N. G.
Published: December 2024

The object of this study is linear magnetic birefringence of light in ferromagnetic materials determined by an addition to the dielectric permittivity of a ferromagnetic crystal, this addition being proportional to the square of the magnetization. Interband s-d exchange interaction of electrons and magnetic atoms is considered as the mechanism for the nonlinearity. The analysis is based on the spin-wave approximation and applies to the range of temperatures T < Tc.
Quantum theory of the linear response of an Ising antiferromagnetic material to a high-frequency magnetic field
Authors: Filatova L. D. , Tsukernik V. M.
Published: December 2024

The high-frequency properties of an antiferromagnetic material described by the Ising model when a weak constant magnetic field is applied perpendicular to the chosen inter-ion anitsotropy axis is investigated. It is shown that certain components of the high-frequency magnetic susceptibility tensor calculated by quantum mechanics differ considerably from the corresponding components obtained using the semiclassical theory.
Dependence of critical vortex formation velocity in helium II upon oscillation period
Authors: Nadirashvili Z. Sh. , Tsakadze Dzh. S.
Published: December 2024

When the critical velocity of vortex formation in helium II is measured by the use of oscillations of axially symmetric bodies, the measured νc proves to be a function of oscillation period and produces false critical velocity values. It is shown that either recalculation of the measured νc values or maintenance of the condition θ ≫ τ (where θ is the oscillation period and τ is the vortex formation delay time) will produce true values of νc which are independent of oscillation period and decrease with growth in temperature, and values of τ which increase as T→Tλ.
Propagation and attenuation of third sound
Authors: Adamenko I. N. , Poluéktov Yu. M.
Published: December 2024

The propagation of finite amplitude third sound waves and their attenuation due to shock wave formation are considered. It is shown that such a mechanism explains the experimentally observed absorption value. The problem of propagation of a low amplitude third sound wave in a film of varying thickness is solved.
Dynamic properties of SNS junctions
Authors: Golub A. A.
Published: December 2024

The case of SNS junctions is considered where the weak link is a metal filament of a small diameter. The dynamic properties of such a system at low voltage are analyzed on the basis of the kinetic equations in the theory of superconductivity. It is demonstrated that the effective resistance of such a junction decreases.
Superfluid vortex formation at rough boundaries
Authors: Krasnov Yu. K.
Published: December 2024

It is shown that roughness of a superfluid boundary lowers the surface energy barrier, which prevents the detachment of quantized vortices from the boundary under the action of the Magnus force exerted by the external flow past the roughness.
Influence of pressure on the electron-phonon interaction in niobium and tantalum
Authors: Revenko Yu. F. , D’yachenko A. I. , Svistunov V. M. , Shonaikh B.
Published: December 2024

The method of electron tunneling is used to study the electron–phonon interaction in niobium and tantalum in the pressure interval 0–9 kbar. It is shown that the superconductivity of these metals is caused by the electron-phonon Cooper pairing mechanism. The method of determining the electron–phonon interaction function from tunnel spectroscopy data of these superconductors is improved.
Impurity-spin relaxation in a one-dimensional X-Y model
Authors: Zaslavskii O. B. , Tsukernik V. M.
Published: December 2024

The time evolution of the impurity spin projection in an X-Y chain on the direction of the external magnetic field is considered for a stepwise change in the field acting on the impurity. The mode of relaxation is substantially dependent on the presence of discrete impurity levels in the system, and also on the closeness of these to the edge of the continuum. Low-temperature and high-temperature cases are considered.
Influence of a magnetic field on the stability of the charged surface of a liquid dielectric
Authors: Monarkha Yu. P.
Published: December 2024

We study theoretically the stability of a charged surface of a liquid dielectric in the presence of a constant magnetic field for various phase states of the electron system. It is shown that a strong magnetic field may significantly increase the stability of the charged surface if the electrons are in the liquid phase. In the case when the electrons form a two-dimensional Wigner crystal, the stability criterion for the surface in the presence of a strong magnetic field is the same as in the absence of a magnetic field.
Kinetics of oriented triplet metastable helium states in gas and liquid phases
Authors: Myshkis D. A. , Luzan E. G.
Published: December 2024

The kinetics of oriented metastable states is examined in a helium plasma afterglow at T ≈ 10 °K and in superfliud helium. The initial conditions given by preliminary optical orientation under total mixing conditions are extended for both the cases under consideration. Their total spin is conserved in bulk processes of destruction of metastable states and the orientation reaches unity. Results are presented for a computation of the kinetics on an electronic computer. The time to achieve complete orientation is less than 10 msec for concentrations of He(23S1) and He2(23Σu+) ≈ 1012 cm3. In the gas phase, the behavior of the inverse concentration is linear in time for a zero initial orientation. In a liquid the features of the kinetics and the optical orientation are related to the formation of microbubbles around the metastable states and electrons. This results in nonmonotonic behavior of the concentration components with zero spin projection.
Hysteresis in the development of instability on a charged liquid surface
Authors: Chernikova D. M.
Published: December 2024

It is demonstrated that on the plane boundary of a deep liquid body with a low surface electron concentration there can be established conditions under which instability of the charged surface will develop with a rather soft but also slightly hysteretic transition. The energy of this new state is determined, this state being characterized by a hexagonal lattice symmetry. This new state is also found to be stable relative to small oscillations.
Pediatric human immunodeficiency virus-positive disclosure status and associated factors among caregivers of children in Wolaita and Hadiya zone, southern Ethiopia
Authors: Tesfaye Lina , Abebe Amene , Molla Simegn , Admasu Amare
Published: December 2024

Background

Human immunodeficiency virus (HIV) positive status disclosure is an essential component of pediatric care and long-term disease management. However, pediatric HIV disclosure is a complex and understudied public health concern. This study aimed to assess the pediatric HIV-positive disclosure status and associated factors among caregivers.

Method

A facility-based cross-sectional study was done among 375 caregivers of HIV-positive children in selected facilities from March 1 to April 30, 2022. Data was collected through inperson interviews using a carefully designed questionnaire that had been tested beforehand. Study participants were randomly selected from the anti-retroviral therapy (ART) logbook using a lottery method as the sampling frame. The data collected was inputted into Epidata version 3.02 and then transferred to SPSS version 23 for analysis. The findings were displayed through tables, graphs, charts, and written descriptions. Statistical analyses using different models were performed to examine the data. The association of variables was declared at 95%CI and p-value <0.05 and the strength of association was determined using the adjusted odds ratio (AOR).

Result

Out of 371 participants, 98.9% replied to the survey. Forty-one point eight percent of caregivers told them about their HIV-positive children’s status. Caregivers/parents’ discussions with health care providers about disclosure [AOR 2.171, 95% CI [1.199, 3.931]], child duration on ART [AOR 1.633, 95% CI [1.013, 2.631]], and child stigmatization [AOR 2.103, 95% CI [1.361, 3.250]] were significantly associated with pediatric HIV positive status disclosure.

Conclusion

The rate of disclosing pediatric HIV-positive status was lower compared to other studies in Ethiopia. Caregivers who talked to healthcare providers, children on ART for a longer time, and caregivers not fearing stigma for their child were more likely to disclose pediatric HIV-positive status. Facility management and healthcare providers should focus on improving the disclosure of pediatric HIV-positive status.
Combined inhibition of MDM2 and PARP lead to a synergistic anti-tumoral response in p53 wild-type rhabdomyosarcoma models
Authors: Pons Guillem , Zarzosa Patricia , Gallo-Oller Gabriel , Wenz Amelie , Lapins Maris , García-Gilabert Lia , Sansa-Girona Júlia , Navarro Natalia , Segura Miguel F. , Soriano Aroa , Guillén Gabriela , Hladun Raquel , Sánchez de Toledo Josep , Gallego Soledad , Carreras-Puigvert Jordi , Moreno Lucas , Roma Josep
Published: December 2024

Targeting MDM2-p53 interaction to enhance p53 activity represents a promising antitumoral strategy for p53 wild-type pediatric tumors, including soft-tissue sarcomas. However, results from early-phase clinical trials in hematological and solid cancers have shown limited efficacy of MDM2 inhibitors, underscoring the necessity to explore more effective combinations with other agents. In this study, we provide results from a 22-drug combination screening demonstrating the therapeutic potential of combining siremadlin (MDM2 inhibitor) and olaparib (PARP inhibitor) for treating p53 wild-type rhabdomyosarcoma (p53 WT RMS). Cell survival, cell death, and apoptosis analysis revealed synergistic effects of combining siremadlin plus olaparibin vitro. The combination of both drugs led to a significant increase in p53 activity, as evidenced by p53 accumulation and K382 acetylation, along with an increased expression of bona fide p53 targets. Furthermore, treatment with both drugs resulted in significant reduction of tumor growth and increased mice overall survival when compared to single treatments and control in cell line-derived orthotopic xenograft models. Overall, our study demonstrates, for the first time, the synergistic effect of combining siremadlin plus olaparib in inhibiting p53 WT RMS tumor growthin vitroandin vivo. Our findings support the potential to study the combination of both drugs in clinical trials and warrants further investigation in other tumors with similar molecular features.
RNA-programmable cell type monitoring and manipulation in the human cortex with CellREADR
Authors: Matthews Elizabeth A. , Russ Jeffrey B. , Qian Yongjun , Zhao Shengli , Thompson Peyton , Methani Muhib , Vestal Matthew L. , Huang Z. Josh , Southwell Derek G.
Published: December 2024

Reliable and systematic experimental access to diverse cell types is necessary for understanding the neural circuit organization, function, and pathophysiology of the human brain. Methods for targeting human neural populations are scarce and currently center around identifying and engineering transcriptional enhancers and viral capsids. Here we demonstrate the utility of CellREADR, a programmable RNA sensor-effector technology that couples cellular RNA sensing to effector protein translation, for accessing, monitoring, and manipulating specific neuron types inex vivohuman cortical tissues. We designed CellREADR constructs to target two distinct human neuron types,CALB2+(calretinin) GABAergic interneurons andFOXP2+ (forkhead box protein P2) glutamatergic projection neurons, and validated cell targeting using histological, electrophysiological, and transcriptomic methods. CellREADR-mediated expression of optogenetic effectors and genetically-encoded calcium indicators allowed us to manipulate and monitor these neuronal populations in cortical microcircuits. We further demonstrate that AAV-based CellREADR and enhancer vectors can be jointly used to target different subpopulations in the same preparation. By demonstrating specific, reliable, and programmable experimental access to targeted cell types, our results highlight CellREADR’s potential for studying human neural circuits and treating brain disorders with cell type resolution.
Exercise alleviates liver senescence but does not outmatch the effect of dietary restriction in diet-induced MASLD
Authors: Katsarou Angeliki , Papadopoulos Grigorios , Moustakas Ioannis I. , Papadopetraki Argyro , Moustogiannis Athanasios , Legaki Aigli-Ioanna , Giannousi Eirini , Veroutis Dimitris , Kotsinas Athanassios , Gorgoulis Vassilis G , Philippou Anastassios , Koutsilieris Michael , Chatzigeorgiou Antonios
Published: December 2024

Background

The present study aims at deciphering the potential benefits of aerobic exercise and dietary restriction on liver senescence, which is an established hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), a condition with limited therapeutic options.

Methods

C57BL6 mice were subjected to normal diet (ND, 10% of kilocalories from fat) or a high-fat diet (HFD, 60% of kilocalories deriving from fat and water supplemented with 5% High-fructose Corn Syrup, HFCS) for 12 weeks. Then, for additional 8 weeks, the ND group continued with the same diet, while the HFD group was divided into four subgroups: a) mice that continued with the same HFD-5% HFCS in water scheme (HFD), b) mice that continued with the same HFD-5% HFCS in water scheme and underwent supervised aerobic exercise 3-times/week (HFDEX), c) mice that were switched to ND (dietary restriction, DR) and d) mice that were switched to ND while undergoing supervised aerobic exercise 3-times/week (DREX). Phenotypic and histological characterization of obesity and MASLD were performed in all groups. Biomarkers of senescence were analyzed in terms of their mRNA expression levels to assess the impact of all interventions on MASLD-related senescence in the liver. GL13 and p21 immunohistochemical stainings were conducted to examine the protein levels of senescence-associated lipofuscin and p21WAF1/CIP1respectively, so as to finally investigate their relationship with the grade of steatosis observed in each individual animal.

Results

DR and DREX groups exhibited significantly reduced features of obesity and MASLD-related hepatic steatosis, to a greater extent than the respective amelioration driven by aerobic exercise-only in HFDEX animals. A statistically significant increase of the mRNA expression of cyclin-dependent kinase p21WAF1/CIP1was detected in HFD livers as compared to ND, which was also reversed upon DR-inclusive interventions. In contrast, the gene expression levels of cyclin-dependent kinase p16INK4aremained similar in all groups even after a combined intervention. Increased hepatic expression of the p27 and p53 components of the p53-p21CIP/WAF-driven axis of cellular senescence as well as their restoration to ND-like levels upon DR and DREX, suggest an active participation of the p21WAF1/CIP1mechanism of senescence in the emergence of MASLD, but also in its reversal through DR or/and EX interventions. Immunohistochemical stainingsforGL13 and p21 confirmed the aforementioned alterations of p21WAF1/CIP1at the tissular level.

Conclusion

Liver senescence is responsive both to exercise and dietary restriction, but its amelioration in the context of MASLD is more robust upon DR-inclusive interventions.
Tokenvizz: GraphRAG-Inspired Tokenization Tool for Genomic Data Discovery and Visualization
Authors: Oğuztüzün Çerağ , Gao Zhenxiang , Xu Rong
Published: December 2024

One of the primary challenges in biomedical research is the interpretation of complex genomic relationships and the prediction of functional interactions across the genome. Tokenvizz is a novel tool for genomic analysis that enhances data discovery and visualization by combining GraphRAG-inspired tokenization with graph-based modeling. In Tokenvizz, genomic sequences are represented as graphs, where sequence k-mers (tokens) serve as nodes and attention scores as edge weights, enabling researchers to visually interpret complex, non-linear relationships within DNA sequences. Through a web-based visualization interface, researchers can interactively explore these genomic relationships and extract biologically meaningful insights about regulatory patterns and functional elements. Applied to promoter-enhancer interaction prediction tasks, Tokenvizz outperformed traditional sequential models while providing interpretable insights into genomic features, demonstrating the advantage of graph-based representations for biological discovery.

Availability and Implementation

Tokenvizz, along with its user guide, is freely accessible on GitHub at:https://github.com/ceragoguztuzun/tokenvizz.

ACM Reference Format

Çerağ Oğuztüzün, Zhenxiang Gao, and Rong Xu. 2024. Tokenvizz: GraphRAG Inspired Tokenization Tool for Genomic Data Discovery and Visualization. InProceedings of (Bioinformatics). ACM, New York, NY, USA, 7 pages.https://doi.org/XXXXXXX.XXXXXXX
Integrating Whole Genome and Transcriptome Sequencing to Characterize the Genetic Architecture of Isoform Variation and its Implications for Health and Disease
Authors: Liu Chunyu , Joehanes Roby , Ma Jiantao , Xie Jiuyong , Yang Jian , Wang Mengyao , Huan Tianxiao , Hwang Shih-Jen , Wen Jia , Sun Quan , Cumhur Demirkale Y. , Heard-Costa Nancy L. , Orchard Peter , Carson April P. , Raffield Laura M. , Reiner Alexander , Li Yun , O’Connor George , Murabito Joanne M. , Munson Peter , Levy Daniel
Published: December 2024

We created a comprehensive whole blood splice variation quantitative trait locus (sQTL) resource by analyzing isoform expression ratio (isoform-to-gene) in Framingham Heart Study (FHS) participants (discovery: n=2,622; validation: n=1,094) with whole genome (WGS) and transcriptome sequencing (RNA-seq) data. External replication was conducted using WGS and RNA-seq from the Jackson Heart Study (JHS, n=1,020). We identified over 3.5 millioncis-sQTL-isoform pairs (p<5e-8), comprising 1,176,624cis-sQTL variants and 10,883 isoform transcripts from 4,971 sGenes, with significant change in isoform-to-gene ratio due to allelic variation. We validated 61% of these pairs in the FHS validation sample (p<1e-4). External validation (p<1e-4) in JHS for the top 10,000 and 100,000 most significantcis-sQTL-isoform pairs was 88% and 69%, respectively, while overall pairs validated at 23%. For 20% ofcis-sQTLs in the FHS discovery sample, allelic variation did not significantly correlate with overall gene expression. sQTLs are enriched in splice donor and acceptor sites, as well as in GWAS SNPs, methylation QTLs, and protein QTLs. We detailed several sentinelcis-sQTLs influencing alternative splicing, with potential causal effects on cardiovascular disease risk. Notably, rs12898397 (T>C) affects splicing ofULK3, lowering levels of the full-length transcript ENST00000440863.7 and increasing levels of the truncated transcript ENST00000569437.5, encoding proteins of different lengths. Mendelian randomization analysis demonstrated that a lower ratio of the full-length isoform is causally associated with lower diastolic blood pressure and reduced lymphocyte percentages. This sQTL resource provides valuable insights into how transcriptomic variation may influence health outcomes.
Co-designed point-of-care ultrasound program development and implementation at a Veterans Affairs Emergency Department
Authors: Theophanous Rebecca G. , Staton Catherine A. , Ragsdale Luna C. , Tupetz Anna , Peethumnongsin Erica , Eucker Stephanie A.
Published: December 2024

Integrating point-of-care ultrasound (POCUS) into patient care requires a multi-faceted culture change using a multi-pronged approach. A standardized implementation method is lacking for POCUS program sustainability. We developed a standardized training curriculum and clinical POCUS documentation, archival, and image review process at a single Veterans Affairs Emergency Department (ED). We hypothesized that co-designed development and implementation of the multifaceted POCUS intervention would maximize ED provider uptake and sustainability.

Using Participatory Action Research (PAR) and adapted Experience-Based Co-design (EBCD) methods, stakeholders collaboratively co-designed our POCUS intervention to optimize implementation. Using the PRODUCES framework, twelve stakeholder participants (co-creators including study researchers, ultrasound faculty, ED leadership, and ED providers (POCUS end-users)) met in four monthly co-design meetings from July to October 2021 to brainstorm, discuss, refine, and finalize the POCUS intervention and implementation plan.

Throughout the co-design process, stakeholders reviewed findings from prior meetings, reflected on successes and failures, and held open discussions on refining and finalizing the proposed POCUS educational and clinical program. By involving stakeholders as co-creators throughout the co-design process, we maximized end-user POCUS enthusiasm, program uptake, and sustained use. This simple, streamlined, and generalizable user-centered co-design method serves as a framework for future POCUS implementation and dissemination plans.
Lifetime incidence and age of onset of mental disorders, and 12-month service utilization in primary and secondary care: a Finnish nationwide registry study
Authors: Suokas Kimmo , Niemi Ripsa , Gutvilig Mai , McGrath John J. , Komulainen Kaisla , Suvisaari Jaana , Elovainio Marko , Lumme Sonja , Pirkola Sami , Hakulinen Christian
Published: December 2024

Previous studies have estimated lifetime incidence, age-specific incidence, age of onset, and service utilization for mental disorders but none have used nationwide data from both primary and secondary care. This study used nationwide Finnish data (2000–2020), including both care settings for the first time. We followed 6.4 million individuals for 98.5 million person-years, calculating cumulative incidence while accounting for competing risks. By age 100, lifetime incidence of any diagnosed mental disorder was 76.7% (95% CI, 76.6–76.7) in women and 69.7% (69.6–69.8) in men. At age 75, stricter estimates for non-organic disorders (ICD-10: F10–F99) were 65.6% (65.5–65.7) for women and 60.0% (59.9–60.1). Anxiety disorders (F40–F48) had the highest cumulative incidence. Median age of onset of non–organic mental disorders was 24.1 (interquartile range 14.8–43.3) in women and 20.0 (7.3–42.2) in men. Service utilization within 12 months was 9.0% for women and 7.7% for men. Most, though not all, individuals experience at least one type of mental disorder, often during youth. Capturing the overall occurrence of mental disorders requires including both primary and secondary care data.
Predicting coronary artery disease severity through genomic profiling and machine learning modelling: The GEnetic SYNTAX Score (GESS) trial
Authors: Chatzopoulou Fani , Mittas Nikolaos , Chatzidimitriou Dimitrios , Giannopoulos-Dimitriou Alexandros , Saiti Aikaterini , Ganopoulou Maria , Karagiannidis Efstratios , Papazoglou Andreas S. , Stalikas Nikolaos , Papa Anna , Giannakoulas George , Sianos Georgios , Angelis Lefteris , Vizirianakis Ioannis S.
Published: December 2024

Cardiovascular diseases (CVDs) present multifactorial pathophysiology and produce immense health and economic burdens globally. The most common type, coronary artery disease (CAD), shows a complex etiology with multiple genetic variants to interplay with various clinical features and demographic traits affecting CAD risk and severity. The development and clinical validation of machine learning (ML) algorithms that integrate genetic biomarkers and clinical features can improve diagnostic accuracy for CAD avoiding, thereby, unnecessary invasive procedures. To this end, we present, here, the development of a data-driven ML approach able to predict the existence and severity of CAD based on the analysis of 228 single nucleotide polymorphisms (SNPs) and clinical and demographic data of 953 patients enrolled in the Genetic Syntax Score (GESS) trial (NCT03150680). Two competing ensemble models (one with clinical predictors and another with clinical plus genetic predictors) were built and evaluated to infer their prediction capabilities. The ensemble model with both clinical and genetic predictors exhibited superior diagnostic performance compared to the competing model with only clinical predictors. The proposed ML framework identified a total of eight contributing SNPs as predictors for the existence of obstructive CAD and seven significant SNPs for the severity of CAD. Such algorithms positively contributes to global efforts aiming to predict the risk and severity of CAD in early stages, thus lowering the cost as well as achieving prognostic, diagnostic, and therapeutic benefits in healthcare and improving patient outcomes in a non-invasive way. Overall, the design and execution of this trial reinforces clinical decision-making and facilitate the harmonization in digitized healthcare within the concept of precision medicine.

Clinical Trial Registration

NCT03150680;https://clinicaltrials.gov/study/NCT03150680?cond=NCT03150680&rank=1
Real-world safety of zonisamide: Mining and analysis of adverse events related to zonisamide based on FAERS database
Authors: Zhang Yongyi , Sun Zhongqian , Li Haoming , Kong Qingxia , Zhang Xuezheng , Li Chengde
Published: December 2024

Purpose

To investigate the real-world adverse event signals associated with zonisamide and provide a foundation for its safe clinical use.

Methods

Adverse event reports involving zonisamide as the primary suspected drug were collected from the FDA Adverse Event Reporting System (FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2023. The data were analyzed utilizing the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods of the proportional imbalance technique.

Results

A total of 3205 adverse event reports involving zonisamide as the primary suspected drug were identified, resulting in 260 positive signals for preferred terms (PTs). These signals, derived from both the ROR and BCPNN methods, encompassed 27 systems and organs (SOCs), with a predominant focus on nervous system disorders and skin and subcutaneous tissue disorders. The most frequently reported PTs included seizures, drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, rash, and dizziness. Notably, the top PTs in terms of signal intensity included perinephritis, epilepsy with myoclonic-atonic, ocular mucocutaneous syndrome, ocular choroidal leakage, tonsillar exudate, and ovarian granulosa vesicular cell tumor. Interestingly, ten of the top 30 risk signals for adverse events, based on signal strength, were not detailed in the package inserts. Thses included perinephritis, myoclonic dystonic epilepsy, ovarian granulosa vesicular cell tumor, positive human herpesvirus 6 serology, and positive lymphocyte stimulation test.

Conclusion

Common adverse reactions to zonisamide in real-world settings are generally in line with the established specification, with the most frequently observer signals related to neurological, skin, and subcutaneous tissue disorders. However, several newly suspected adverse reactions have been identified, including perinephritis, infectious pneumonitis, ovarian granulosa vesicular cell tumor, positive serology for human herpesvirus 6, and positive lymphocyte stimulation test. These findings indicate that these potential adverse reactions should be closely monitored in clinical practice.
Serious psychological distress among people with unstable housing in Ho Chi Minh City, Vietnam: Prevalence and associated factors
Authors: Murakami Hitoshi , Linh Nguyen Thuy , Fujita Masami , Thuy Lam Ngoc , Phuc Nguyen Hong , Mai Huong Kieu Thi , Anh Le Tuan , Ngoc Mai Pham Thi , Hai Oanh Khuat Thi
Published: December 2024

Purpose

This study aimed to estimate the prevalence of serious psychological distress (SPD) among slum dwellers and homeless individuals in Ho Chi Minh City, Vietnam, and to identify factors associated with SPD.

Method

A cross-sectional survey of 415 individuals with unstable housing, including 383 slum dwellers and 32 homeless individuals, was conducted from November 2023 to April 2024. Data were collected using a structured questionnaire that included the Kessler Psychological Distress Scale (K6).

Results

The prevalence of SPD was 19.8% (18.5% among slum dwellers and 34.4% among the homeless). Multiple logistic regression revealed significant associations between SPD and female gender (p=0.000), labor exploitation (p=0.046), and debt (p=0.000). Notably, 68.7% of participants reported experiencing some form of labor exploitation, commonly involving contract rejections, forced overwork, wage theft, and physical or verbal abuse. Additionally, 43.7% were in debt, with 38.6% borrowing from moneylenders.

Conclusions

The prevalence of SPD among individuals with unstable housing in Ho Chi Minh City was significantly higher than that of the general population. Those with SPD frequently faced both labor and economic exploitation, without insufficient social protection. In terms of labor exploitation, policy interventions, particularly from an occupational health perspective, are necessary. To address economic exploitation through debt, given the prevalence of loan sharks, efforts to crack down on predatory lending and promote financial inclusion are essential.