bluuebunny/crossref_metadata_2025 huggingface dataset:
Wnt, glucocorticoid and cellular prion protein cooperate to drive a mesenchymal phenotype with poor prognosis in colon cancer
Authors: Mouillet-Richard Sophie , Gougelet Angélique , Passet Bruno , Brochard Camille , Le Corre Delphine , Pitasi Caterina Luana , Joubel Camille , Sroussi Marine , Gallois Claire , Lavergne Julien , Castille Johan , Vilotte Marthe , Daniel-Carlier Nathalie , Pilati Camilla , de Reyniès Aurélien , Djouadi Fatima , Colnot Sabine , André Thierry , Taieb Julien , Vilotte Jean-Luc , Romagnolo Béatrice , Laurent-Puig Pierre
Published: April 2024

Background

The mesenchymal subtype of colorectal cancer (CRC), associated with poor prognosis, is characterized by abundant expression of the cellular prion protein PrPC, which represents a candidate therapeutic target. How PrPC is induced in CRC remains elusive. This study aims to elucidate the signaling pathways governing PrPC expression and to shed light on the gene regulatory networks linked to PrPC.

Methods

We performed in silico analyses on diverse datasets of in vitro, ex vivo and in vivo models of mouse CRC and patient cohorts. We mined ChIPseq studies and performed promoter analysis. CRC cell lines were manipulated through genetic and pharmacological approaches. We created mice combining conditional inactivation of Apc in intestinal epithelial cells and overexpression of the human prion protein gene PRNP. Bio-informatic analyses were carried out in two randomized control trials totalizing over 3000 CRC patients.

Results

In silico analyses combined with cell-based assays identified the Wnt-β-catenin and glucocorticoid pathways as upstream regulators of PRNP expression, with subtle differences between mouse and human. We uncover multiple feedback loops between PrPC and these two pathways, which translate into an aggravation of CRC pathogenesis in mouse. In stage III CRC patients, the signature defined by PRNP-CTNNB1-NR3C1, encoding PrPC, β-catenin and the glucocorticoid receptor respectively, is overrepresented in the poor-prognosis, mesenchymal subtype and associates with reduced time to recurrence.

Conclusions

An unleashed PrPC-dependent vicious circle is pathognomonic of poor prognosis, mesenchymal CRC. Patients from this aggressive subtype of CRC may benefit from therapies targeting the PRNP-CTNNB1-NR3C1 axis.
Devastating fungal endocarditis involving ascending aorta in a patient with a history of aortic valve replacement: a case report
Authors: Koohsari Parisa , Nakhaee Akram , Rahmanian Mehrzad , Salahshour Faeze , Parkhideh Roya , Larti Farnoosh
Published: April 2024

Background

Fungal endocarditis is a rare but serious condition associated with high mortality rates. Various predisposing factors contribute to its occurrence, such as underlying cardiac abnormalities, cardiac surgeries, prosthetic cardiac devices, and central venous catheters. Diagnosing fungal endocarditis, particularly Aspergillus, poses challenges, often complicated by negative blood cultures.

Case presentation

This report details a case of extensive ascending aorta involvement in Aspergillus endocarditis (AE) in a 24-year-old man with a history of bioprosthesis aortic valve replacement (AVR). Three months post-AVR, he presented with pericardial effusion and aortic rupture, leading to a redo biological valved conduit aortic root replacement (Bentall surgery). Despite the intervention, the tubular graft exhibited extensive Aspergillus involvement, resulting in graft disruption and significant peri-aortic infection. A second redo procedure involving aortic homograft root replacement was performed. Unfortunately, the patient succumbed two days after the surgery.

Conclusion

A combined approach of medical and surgical therapies is recommended to manage fungal endocarditis. Despite efforts, the mortality rate associated with Aspergillus endocarditis remains unacceptably high, with no significant difference observed between combination therapy and antifungal treatment alone. Further research is essential to explore novel therapeutic strategies and improve outcomes for patients with this challenging condition.
Optimal patient selection for maze procedure in patients undergoing mitral valve disease
Authors: Masuda Tomoaki , Aoki Atsushi , Omoto Tadashi , Maruta Kazuto
Published: April 2024

Objectives

Although risk factors for unsuccessful Maze procedure have been demonstrated, an appropriate patient selection is still controversial. In our institute, Maze procedure is indicated for those whom normal sinus rhythm (NSR) was reestablished by intraoperative direct cardioversion (DC) after ventricular unloading by total cardiopulmonary bypass. The purpose of this study was to evaluate the effectiveness of our indication criteria for Maze procedure in patients with mitral valve disease.

Methods

Between October 2012 and October 2021, MAZE was indicated in 55 patients in whom normal sinus rhythm (NSR) was reestablished by intraoperative direct current cardioversion (DC). Three endpoints and predictors were examined: disappearance of atrial fibrillation (AF), NSR, and A-wave detection.

Results

Restoration of NSR by intraoperative DC was confirmed in 43 patients, and these patients underwent MAZE. AF disappeared in 39 patients (90.7%), and F-wave ≥ 0.1 mV was a significant predictive factor (odds ratio (OR) 20.99, 95% CI 1.22–1079.06). NSR was reestablished in 36 patients (83.7%), and F-wave ≥ 0.1 mV (odds ratio 15.62, 95% CI 1.62–359.86) + AF history ≤ 3 years (OR 8.30, 95% CI 1.09–177.04) were significant predictors. A-wave detection was confirmed in 26 patients (60.5%), and left atrial diameter ≤ 55 mm was a significant predictor (OR 5.22, 95% CI 1.28–24.79).

Conclusions

Intraoperative DC after ventricular unloading resulted effective patient selection for concomitant Maze procedure. F-wave and AF history were predictive factor of electrical restoration of AF, and left atrial diameter was predictive factor of restoration of atrial function.
The Red Cross Red Crescent Health Information System (RCHIS): an electronic medical records and health information management system for the red cross red crescent emergency response units
Authors: Holl Felix , Clarke Lauren , Raffort Thomas , Serres Elvire , Archer Laura , Saaristo Panu
Published: April 2024

Background

The Red Cross and Red Crescent Movement (RCRC) utilizes specialized Emergency Response Units (ERUs) for international disaster response. However, data collection and reporting within ERUs have been time-consuming and paper-based. The Red Cross Red Crescent Health Information System (RCHIS) was developed to improve clinical documentation and reporting, ensuring accuracy and ease of use while increasing compliance with reporting standards.

Case presentation

RCHIS is an Electronic Medical Record (EMR) and Health Information System (HIS) designed for RCRC ERUs. It can be accessed on Android tablets or Windows laptops, both online and offline. The system securely stores data on Microsoft Azure cloud, with synchronization facilitated through a local ERU server. The functional architecture covers all clinical functions of ERU clinics and hospitals, incorporating user-friendly features. A pilot study was conducted with the Portuguese Red Cross (PRC) during a large-scale event. Thirteen super users were trained and subsequently trained the staff. During the four-day pilot, 77 user accounts were created, and 243 patient files were documented. Feedback indicated that RCHIS was easy to use, requiring minimal training time, and had sufficient training for full utilization. Real-time reporting facilitated coordination with the civil defense authority.

Conclusions

The development and pilot use of RCHIS demonstrated its feasibility and efficacy within RCRC ERUs. The system addressed the need for an EMR and HIS solution, enabling comprehensive clinical documentation and supporting administrative reporting functions. The pilot study validated the training of trainers’ approach and paved the way for further domestic use of RCHIS. RCHIS has the potential to improve patient safety, quality of care, and reporting efficiency within ERUs. Automated reporting reduces the burden on ERU leadership, while electronic compilation enhances record completeness and correctness. Ongoing feedback collection and feature development continue to enhance RCHIS’s functionality. Further trainings took place in 2023 and preparations for international deployments are under way. RCHIS represents a significant step toward improved emergency medical care and coordination within the RCRC and has implications for similar systems in other Emergency Medical Teams.
PMF-GRN: a variational inference approach to single-cell gene regulatory network inference using probabilistic matrix factorization
Authors: Skok Gibbs Claudia , Mahmood Omar , Bonneau Richard , Cho Kyunghyun
Published: April 2024

Inferring gene regulatory networks (GRNs) from single-cell data is challenging due to heuristic limitations. Existing methods also lack estimates of uncertainty. Here we present Probabilistic Matrix Factorization for Gene Regulatory Network Inference (PMF-GRN). Using single-cell expression data, PMF-GRN infers latent factors capturing transcription factor activity and regulatory relationships. Using variational inference allows hyperparameter search for principled model selection and direct comparison to other generative models. We extensively test and benchmark our method using real single-cell datasets and synthetic data. We show that PMF-GRN infers GRNs more accurately than current state-of-the-art single-cell GRN inference methods, offering well-calibrated uncertainty estimates.
Assessment of hypoxemia among young adults with sickle cell anaemia in steady state in southwestern Nigeria: a crosssectional study
Authors: M. A. Asafa , O Ahmed I. , M. S. Afolabi , A. Bolarinwa R. , O. Ogunlade
Published: April 2024

Objectives

Hypoxia is a known feature of sickle cell anaemia (SCA) which results from chronic anaemia and recurrent vaso-occlusive crisis (VOC) which can cause tissue ischaemia that leads to an end organ damage. The hallmark of SCA is chronic anaemia and recurrent vaso-occlusive crisis. The aim of this study is to compare the oxygen saturation of sickle cell anaemic individuals with the normal haemoglobin type (Hb AA) control and also to determine the prevalence of hypoxemia among SCA.

Results

Two-hundred and twenty-two (136 Hb SS and 86 Hb AA) participated in the study. The mean ± SD of age (years), oxygen saturation (%) and pulse rate (bpm) of participants with sickle cell anaemia and Hb AA control were 21.85 ± 3.04 and 22.14 ± 3.18 (t = 0.701, p = 0.436), 95.21 ± 3.02 and 98.07 ± 0.81 (t=-8.598, p < 0.0001) and 77.10 ± 9.28 and 73.16 ± 8.52 (t = 3.173, p = 0.002) respectively. The prevalence of hypoxemia among SCA participants was 47.1%. Prevalence of hypoxemia in males with SCA was 60.9% while 39.1% of the females had hypoxemia.
Swine acute diarrhea syndrome coronavirus nucleocapsid protein antagonizes the IFN response through inhibiting TRIM25 oligomerization and functional activation of RIG-I/TRIM25
Authors: Zhang Jiyu , Shi Hongyan , Zhang Liaoyuan , Feng Tingshuai , Chen Jianfei , Zhang Xin , Ji Zhaoyang , Jing Zhaoyang , Zhu Xiaoyuan , Liu Dakai , Yang Xiaoman , Zeng Miaomiao , Shi Da , Feng Li
Published: April 2024

Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging Alpha-coronavirus, brings huge economic loss in swine industry. Interferons (IFNs) participate in a frontline antiviral defense mechanism triggering the activation of numerous downstream antiviral genes. Here, we demonstrated that TRIM25 overexpression significantly inhibited SADS-CoV replication, whereas TRIM25 deficiency markedly increased viral yield. We found that SADS-CoV N protein suppressed interferon-beta (IFN-β) production induced by Sendai virus (SeV) or poly(I:C). Moreover, we determined that SADS-CoV N protein interacted with RIG-I N-terminal two caspase activation and recruitment domains (2CARDs) and TRIM25 coiled-coil dimerization (CCD) domain. The interaction of SADS-CoV N protein with RIG-I and TRIM25 caused TRIM25 multimerization inhibition, the RIG-I-TRIM25 interaction disruption, and consequent the IRF3 and TBK1 phosphorylation impediment. Overexpression of SADS-CoV N protein facilitated the replication of VSV-GFP by suppressing IFN-β production. Our results demonstrate that SADS-CoV N suppresses the host IFN response, thus highlighting the significant involvement of TRIM25 in regulating antiviral immune defenses.
Multiplicity and nonexistence of positive solutions to impulsive Sturm–Liouville boundary value problems
Authors: Yang Xuxin , Liu Piao , Wang Weibing
Published: April 2024

In this paper, we study the existence, nonexistence, and multiplicity of positive solutions to a nonlinear impulsive Sturm–Liouville boundary value problem with a parameter. By using a variational method, we prove that the problem has at least two positive solutions for the parameter $\lambda \in (0,\Lambda )$
λ
∈
(
0
,
Λ
)
, one positive solution for $\lambda =\Lambda $
λ
=
Λ
, and no positive solution for $\lambda >\Lambda $
λ
>
Λ
, where $\Lambda >0$
Λ
>
0
is a constant.
Combining machine translation and automated scoring in international large-scale assessments
Authors: Jung Ji Yoon , Tyack Lillian , von Davier Matthias
Published: April 2024

Background

Artificial intelligence (AI) is rapidly changing communication and technology-driven content creation and is also being used more frequently in education. Despite these advancements, AI-powered automated scoring in international large-scale assessments (ILSAs) remains largely unexplored due to the scoring challenges associated with processing large amounts of multilingual responses. However, due to their low-stakes nature, ILSAs are an ideal ground for innovations and exploring new methodologies.

Methods

This study proposes combining state-of-the-art machine translations (i.e., Google Translate & ChatGPT) and artificial neural networks (ANNs) to mitigate two key concerns of human scoring: inconsistency and high expense. We applied AI-based automated scoring to multilingual student responses from eight countries and six different languages, using six constructed response items from TIMSS 2019.

Results

Automated scoring displayed comparable performance to human scoring, especially when the ANNs were trained and tested on ChatGPT-translated responses. Furthermore, psychometric characteristics derived from machine scores generally exhibited similarity to those obtained from human scores. These results can be considered as supportive evidence for the validity of automated scoring for survey assessments.

Conclusions

This study highlights that automated scoring integrated with the recent machine translation holds great promise for consistent and resource-efficient scoring in ILSAs.
Isoflurane, like sepsis, decreases CYP1A2 liver enzyme activity in intensive care patients: a clinical study and network model
Authors: Köhler Thomas , Schwier Elke , Praxenthaler Janina , Kirchner Carmen , Winde Günther , Koos Björn , Henzler Dietrich
Published: April 2024

Purpose

Liver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect.

Methods

In this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation.

Results

The mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg−1 h−1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg−1 h−1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence.

Conclusion

Sepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.
Bilateral thoracotomy for horseshoe lung complicated with severe aspergilloma: a case report
Authors: Kagohashi Chihiro , Kurihara Yasuyuki , Hanafusa Mariko , Okubo Kenichi
Published: April 2024

Background

Horseshoe lung is a rare congenital malformation in which the lung protrudes from the mediastinum to the other side. Owing to the high frequency of other fatal cardiovascular complications, it is often diagnosed in childhood and rarely unnoted until adulthood. We report a case of horseshoe lung in an older patient who underwent thoracotomy.

Case presentation

The patient was a 69-year-old man with chronic obstructive pulmonary disease (COPD) and a history of heavy smoking. The patient was admitted to the hospital because of acute exacerbation of COPD. Computed tomography revealed horseshoe lung and pulmonary sequestration with pneumonia. This was the first time that he was diagnosed with horseshoe lung; however, he had been treated for pneumonia multiple times before. Surgery for the horseshoe lung was recommended; however, the patient declined it because his symptoms of acute COPD exacerbation were relieved by medication. Aspergillus infection of the horseshoe lung led to frequent bloody sputum, and the patient’s respiratory condition gradually worsened. Two years after the initial diagnosis, the patient decided to undergo the surgery. Surgery was performed in the order of left and right thoracotomies, with posterolateral thoracotomies performed bilaterally. Surgery was difficult because of strong adhesions around the inflamed lung; however, the lung was removed in one lump. The patient was extubated on postoperative day (POD) 1, and rehabilitation was initiated. His high sputum volume caused postoperative pneumonia, and the patient was again placed on a ventilator on POD 9. He underwent open-window surgery for concomitant pyothorax. The patient was weaned off the ventilator when the inflammation improved and was discharged on POD 133. The patient lived at home, developed severe pneumonia 4 months later, and died of respiratory failure.

Conclusion

Pulmonary sequestration and horseshoe lungs are congenital malformations that require surgery. The selection of the optimal time for surgery is important.
Evaluating photodynamic therapy versus brolucizumab as a second-line treatment for polypoidal choroidal vasculopathy
Authors: Funatsu Ryoh , Terasaki Hiroto , Mihara Naohisa , Sonoda Shozo , Shiihara Hideki , Sakamoto Taiji
Published: April 2024

Background

To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy.

Methods

This case–control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders.

Results

Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01 ± 0.47 logMAR vs. 0.04 ± 0.18 logMAR, P-value = 0.756; CMT: − 36.3 ± 99.4 μm vs. − 114.7 ± 181.4 μm, P-value = 0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42–2070.07, P-value = 0.019). The E-value for the adjusted odds ratio was 23.44.

Conclusions

Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.
The overlap of accessory virulence factors and multidrug resistance among clinical and surveillance Klebsiella pneumoniae isolates from a neonatal intensive care unit in Nepal: a single-centre experience in a resource-limited setting
Authors: Shrestha Raj Kumar , Shrestha Dhruba , Kunwar Ajaya Jang , Thapa Sandeep , Shrestha Nipun , Dhoubhadel Bhim Gopal , Parry Christopher M.
Published: April 2024

Background

There is a lack of data on the characteristics of overlap between acquired antimicrobial resistance and virulence factors in Klebsiella pneumoniae in high-risk settings, especially with the inclusion of surveillance isolates along with the clinical. We investigated K. pneumoniae isolates, from a neonatal intensive care unit (NICU) in Nepal, for the presence of both accessory virulence factors and acquired antimicrobial resistance.

Methods

Thirty-eight clinical and nineteen surveillance K. pneumoniae isolates obtained between January 2017 and August 2022 in the NICU of Siddhi Memorial Hospital, Bhaktapur, Nepal were investigated with antimicrobial susceptibility testing, PCR-based detection of β-lactamases and virulence factors, and genetic similarity by ERIC–PCR.

Results

K. pneumoniae was found positive in 37/85 (43.5%) blood culture-positive neonatal bloodstream infections, 34/954 (3.6%) patient surveillance cultures, and 15/451 (3.3%) environmental surveillance samples. Among 57 isolates analyzed in this study, we detected multidrug resistance in 37/57 (64.9%), which was combined with at least one accessory virulence factor in 21/37 (56.8%). This overlap was mostly among β-lactamase producing isolates with accessory mechanisms of iron acquisition. These isolates displayed heterogenous ERIC–PCR patterns suggesting genetic diversity.

Conclusions

The clinical significance of this overlap between acquired antimicrobial resistance and accessory virulence genes in K. pneumoniae needs further investigation. Better resource allocation is necessary to strengthen infection prevention and control interventions in resource-limited settings.
An intelligent heating system based on the Internet of Things and STM32 microcontroller
Authors: Su Yan
Published: April 2024

Under the rapid growth of Internet of Things technology, many households are moving towards smart solutions. Addressing the inflexibility of temperature control in traditional heating systems, this research focuses on designing an intelligent heating system. To enhance flexibility and intelligence, an intelligent heating system based on the Internet of Things and STM32 microcontroller is proposed. Furthermore, the study identifies limitations of traditional proportional-integral-derivative control methods and establishes an optimization control model for heating system output temperature based on the Dynamic Matrix Control algorithm. Results indicate that the system's web interface successfully draws temperature curves, displaying clear data on detected temperature and humidity. The output temperature optimization control model shows a temperature rise of 2 °C and a temperature control error index of 0.0543 during the initial heating stage, and a control error index of 0.0353 during the mid-heating stage when the valve relative opening is close to 0. And the temperature control effect is better than traditional PID control, fuzzy PID control, genetic algorithm based PID control, and predictive feedback predictive control, without obvious indoor temperature overshoot phenomenon, which has certain advantages. In conclusion, the proposed system and model exhibit favorable application outcomes, offering technological support for the intelligent management of heating systems.
A comparative study in left-sided breast cancer treated with moderate deep inspiratory breath hold versus free breathing
Authors: Muraleedharan Anupam , Barik Sandip Kumar , Das Deepak Kumar , Das Majumdar Saroj Kumar , Mahapatra Bikash Ranjan , Barik Bijay Kumar , Ramasubbu Mathan Kumar , M. Nehla Haroon K. , U. Poornima Devi , Ahmed Sk Soel , Mukherjee Priyanka , Pattanaik Ashutosh , Badajena Avinash , Mishra Minakshi , Kanungo Satyabrata , Dhar Sovan Sarang , Parida Dillip Kumar
Published: April 2024

Background

The moderate deep inspiratory breath hold (mDIBH) is a modality famed for cardiac sparing. Prospective studies based on this are few from the eastern part of the world and India. We intend to compare the dosimetry between mDIBH and free-breathing (FB) plans.

Methods

Thirty-two locally advanced left breast cancer patients were taken up for the study. All patients received a dose of 50 Gy in 25 fractions to the chest wall/intact breast, followed by a 10-Gy boost to the lumpectomy cavity in the case of breast conservation surgery. All the patients were treated in mDIBH using active breath coordinator (ABC). The data from the two dose volume histograms were compared regarding plan quality and the doses received by the organs at risk. Paired t-test was used for data analysis.

Results

The dose received by the heart in terms of V5, V10, and V30 (4.55% vs 8.39%) and mean dose (4.73 Gy vs 6.74 Gy) were statistically significant in the ABC group than that in the FB group (all p-values < 0.001). Also, the dose received by the LADA in terms of V30 (19.32% vs 24.87%) and mean dose (32.99 Gy vs 46.65 Gy) were significantly less in the ABC group. The mean treatment time for the ABC group was 20 min, while that for the free-breathing group was 10 min.

Conclusions

Incorporating ABC-mDIBH for left-sided breast cancer radiotherapy significantly reduces the doses received by the heart, LADA, and left and right lung, with no compromise in plan quality but with an increase in treatment time.
Global perspectives on bipolar disorder treatment: in-depth comparative analysis of international guidelines for medication selection
Authors: Park Ji Hyun , Fernando Kaveesha , Park Youngja Hwang , Park Esther O.
Published: April 2024

Background

Bipolar disorder, a chronic mental health condition characterised by fluctuations in mood, energy and functionality, affects millions of individuals worldwide. Its management requires a comprehensive approach, and, as such, treatment guidelines have a pivotal role in guiding clinicians to alleviate symptoms, prevent relapse and enhance overall patient well-being. However, the treatment landscape is far from homogenous, with significant variations existing across different countries.

Aims

This study aimed to explore and compare treatment guidelines for bipolar disorder in various regions, shedding light on the factors that influence therapeutic approaches and thus offering insights that could contribute to the ongoing refinement of evidence-based practices in management.

Method

The study explores various international treatment guidelines for bipolar disorder that have been updated after 2014. Guidelines from the UK, Canada, Australia/New Zealand, South Korea and the International College of Neuropsychopharmacology are scrutinised to identify factors contributing to the observed differences among them.

Results

The variations in recommended drugs across guidelines arise from the approaches employed in guideline development – whether relying on expert consensus or meta-analysis results. Timing disparities in conducting these analyses and the selection of studies also exert influence. Moreover, differences in metabolic enzymes among diverse races and the health policies implemented by individual nations play a significant part in shaping these differences.

Conclusion

The primary hindrance to consistent treatment conclusions lies in the scarcity of high-quality research results, leading to variations in guidelines. Enhancing evidence-based recommendations necessitates the undertaking of large-scale studies dedicated to assessing treatments for bipolar disorder.
Scaling of buccal mass growth and muscle activation determine the duration of feeding behaviors in the marine mollusc Aplysia californica
Authors: Rogers Stephen M. , Gill Jeffery P. , De Campos Ana Skalski , Wang Katherine , Kaza Isha V. , Fan Victoria X. , Sutton Gregory P. , Chiel Hillel J.
Published: April 2024

The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviors, which may both be affected by size-dependent scaling. The mechanics of slow movements in small animals are dominated by elastic forces and are thus quasistatic (i.e., always near mechanical equilibrium). Muscular forces producing movement and elastic forces resisting movement should both scale identically (proportional to mass⅔), leaving the scaling of the time constant of muscle activation to play a critical role in determining behavioral duration. We tested this hypothesis by measuring the duration of feeding behaviors in the marine mollusc Aplysia californica whose body sizes spanned three orders of magnitude. The duration of muscle activation was determined by measuring the time it took for muscles to produce maximum force as Aplysia attempted to feed on tethered inedible seaweed, which provided an in vivo approximation of an isometric contraction. The timing of muscle activation scaled with mass0.3. The total duration of biting behaviors scaled identically, with mass0.3, indicating a lack of additional mechanical effects. The duration of swallowing behavior, however, exhibited a shallower scaling of mass0.17. We suggest that this was due to the allometric growth of the anterior retractor muscle during development, as measured by micro computed tomography scans (microCT) of buccal masses. Consequently, larger Aplysia did not need to activate their muscles as fully to produce equivalent forces. These results indicate that muscle activation may be an important determinant of the scaling of behavioral durations in quasistatic systems.
The effects of muscle starting length on work loop power output of isolated mouse soleus and extensor digitorum longus muscle
Authors: Shelley Sharn P. , James Rob S. , Tallis Jason
Published: April 2024

Force–length relationships derived from isometric activations may not directly apply to muscle force production during dynamic contractions. As such, different muscle starting lengths between isometric and dynamic conditions could be required to achieve maximal force and power. Therefore, this study examined the effects of starting length [±5–10% of length corresponding to maximal twitch force (L0)] on work loop (WL) power output (PO), across a range of cycle frequencies, of the soleus (SOL) and extensor digitorum longus muscle (EDL; N=8–10) isolated from ∼8 week old C57 mice. Furthermore, passive work was examined at a fixed cycle frequency to determine the association of passive work and active net work. Starting length affected maximal WL PO of the SOL and EDL across evaluated cycle frequencies (P<0.030, ηp2>0.494). For the SOL, PO produced at −5% L0 was greater than that at most starting lengths (P<0.015, Cohen's d>0.6), except −10% L0 (P=0.135, d<0.4). However, PO produced at −10% L0 versus L0 did not differ (P=0.138, d=0.35-0.49), indicating −5% L0 is optimal for maximal SOL WL PO. For the EDL, WL PO produced at −10% L0 was lower than that at most starting lengths (P<0.032, d>1.08), except versus −5% L0 (P=0.124, d<0.97). PO produced at other starting lengths did not differ (P>0.163, d<1.04). For the SOL, higher passive work was associated with reduced PO (Spearman's r=0.709, P<0.001), but no relationship was observed between passive work and PO of the EDL (Pearson's r=0.191, r2=0.04, P=0.184). This study suggests that starting length should be optimised for both static and dynamic contractions and confirms that the force–length curve during dynamic contractions is muscle specific.
ANÁLISE DA EFETIVIDADE TEMPORAL NA GESTÃO DOS PROCESSOS DE AQUISIÇÕES EM UNIDADES GESTORAS EXECUTORAS
Authors: Morrudo Anderson Luis Raldi
Published: April 2024

As aquisições no contexto das instituições públicas assumem, atualmente, uma relevância estratégica. A elaboração dos processos de uma significativa parte dessas aquisições é lenta, produzindo efeitos negativos na eficiência, na economia e na oportunidade dos bens ou serviços a serem adquiridos. A intenção desta pesquisa foi analisar a efetividade temporal dos processos de aquisição identificando os fatores que provocam a falta de celeridade na sua elaboração. Este estudo qualitativo, utilizando-se do método quantitativo, foi baseado no questionário aplicado nas UGEs, em uma pesquisa bibliográfica e processual e em entrevistas com a Consultoria Jurídica, órgão de assessoria jurídica que realiza a análise dos processos de aquisição. Os achados do estudo apontam para a perda de efetividade na elaboração processual das compras públicas, provocada por fatores internos e externos às UGEs. A conclusão do estudo propõe a implementação de medidas voltadas para a melhoria da gestão dos processos, visando mitigar os impactos negativos identificados.
Latest discoveries related to taste and smell disorders in
patients with post-COVID-19 and other neuroviruses – a
systematic literature review
Authors: Goldstein Horia , Onose Gelu , Azamfirei Bianca , Muresanu Dafin F.
Published: April 2024

Abstract: Introduction: The SARS CoV-2 infection, responsible for COVID-19, has spread worldwide starting with the end of 2019, with major impact in the years 2020 and 2021, especially through the alpha, beta, and delta strains respectively. These strains have also been associated with the development of symptoms of anosmia and ageusia, even after overcoming the acute form of the disease, as part of the post-COVID-19 sequalae that make up the so-called “long-Covid”. [1] The purpose of this systematic literature review was to study these disabling symptoms in the context of long-COVID syndrome.
Material and methods: In order to accomplish this review, we used the method Preferred Reporting Items for Systematic Reviews and Meta-Analyses (acronym - PRISMA) to filter and select the articles of interest that appeared in the period 1/01/2021-31/12/2022, in the international medical databases: Elsevier, NCBI/ PubMed,NCBI/ PMC and PEDro (= Physiotherapy Evidence Database classification), as well as ISI Web of Knowledge (Institute for Scientific Information - ex Thomson Reuters - Clarivate Analytics). We used the keywords for the selection: "COVID-19" / "viral neuroinfections" + "smell" /”olphactory” + "taste" /”gustatory”+ "anosmia" + 'ageusia' +'recovery'+'rehabilitation'.
Results and discussion: After applying indirect and then direct quantitative and qualitative filtering, 25 articles remained that met the selection criteria (noted in order of relevance in table 1, at the end of the article). We also added a number of freely identified papers, considered relevant to our topic. We studied aspects of the "long-COVID" syndrome, mainly related to neuro-psychiatric symptoms - especially taste and smell disorders (anosmia/ageusia), risk factors, predictors for this status, pathophysiology, their intricate mechanism of action, frequency of symptoms, neuroanatomy imaging correlated with clinical aspects, effect of anosmia and ageusia on quality of life, recovery from such sequelae, favorable/unfavorable prognostic factors in this regard.
Conclusions: Smell and taste are more than just simple sensations/perceptions and anosmia/ ageusia does not always recover spontaneously. The category of patients who are left with such permanent qualitative/quantitative alterations requires in-depth study in order to establish standardized and more effective methods of diagnosis, evaluation and treatment and recovery, than those available at the moment. The chosen topic represents a partially studied niche in the current well of knowledge, which will allow us, following the theoretical and practical deepening of the subject, some possible elements of future contribution.
The role of periodontal treatment in comprehensive cardiac
rehabilitation
Authors: Caloian Carmen Silvia , Pop Dana , Caloian Bogdan , Ciurea Andreea , Stanomir Alina , Micu Iulia Cristina , Soancă Andrada , Roman Alexandra
Published: April 2024

Abstract: (1) Background: Periodontitis is a chronic infectious, inflammatory disease associated with significant local disastrous effects due to alveolar bone destruction and systemic morbidities. Some associations between periodontitis and coronary and cerebrovascular diseases have been highlighted in the literature. The present study investigated a group of patients with atherosclerotic cardiovascular diseases and periodontitis and aimed to as-sess the comprehensive effects of nonsurgical periodontitis treatment. (2) Methods: The present study included 11 patients with atherosclerotic cardiovascular disease and perio-dontitis, that were diagnosed after a complete and a complex periodontal evaluation. These patients received periodontal treatment and periodontal reevaluation after 2 months from initial therapy. (3) Results: A significant improvement of the oral hygiene and gingival bleeding scores was recorded at two months follow-up. For moderate pockets of 5 mm, there was a significant reduction of their median values at two months follow-up moment (p=0.021). (4) Conclusion: The nonsurgical periodontal treatment significantly improves the clinical-related parameters of the periodontal tissues, as revealed by gingival bleeding and pocket closure.
Μοριακή μελέτη των μικρών ανευρυσμάτων κοιλιακής αορτής και αναζήτηση βιοδεικτών για την ανευρυσματική νόσο της κοιλιακής αορτής
Authors: Τασοπούλου Καλλιόπη-Μαρία
Published: April 2024

Εισαγωγή: Τα μικρά ανευρύσματα κοιλιακής αορτής είναι συνήθως ασυμπτωματικά και ανιχνεύονται ως τυχαίο εύρημα σε απεικονιστικούς ελέγχους για διερεύνηση άλλων παθολογιών. Επί του παρόντος, η διάγνωση της ανευρυσματικής νόσου γίνεται με απεικονιστικές μεθόδους. Η ανάδειξη βιοδεικτών αποτελεί ένα επιπλέον βήμα προς την έγκαιρη διάγνωση, πριν την εμφάνιση επιπλοκών όπως η ρήξη, που είναι δυνητικά θανατηφόρα. Τα microRNA έχουν αποδειχτεί καλής ποιότητας βιοδείκτες για μεγάλο αριθμό παθολογιών, συμπεριλαμβανομένων και των ανευρυσμάτων κοιλιακής αορτής. Σκοπός:Ο σκοπός της παρούσας εργασίας ήταν, μέσω της ανίχνευσης microRNA με διαφορική έκφραση στα μικρά ανευρύσματα κοιλιακής αορτής, να δημιουργηθεί μια εν δυνάμει αντιπροσωπευτική ομάδα microRNA καθώς και η περαιτέρω επαλήθευση της έκφρασης ενός εξ’αυτών, ως πιθανό βιοδείκτη, στον ορό ασθενών. Μέθοδοι: Το αρχικό στάδιο ανίχνευσης της διαφορικής έκφρασης των microRNA πραγματοποιήθηκε με τη μέθοδο Next-Generation Sequencing σε τρεις ομάδες δειγμάτων (9 στοσύνολο, 3 από κάθε ομάδα), τα μικρά ανευρύσματα κοιλιακής αορτής συγκριτικά με μεγάλα ανευρύσματα, και τα δείγματα ελέγχου. Για το δεύτερο στάδιο, επιλέχθηκε το miR-24, για επαλήθευση της έκφρασης του με τη μέθοδο Real – time PCR σε μεγαλύτερη ομάδα δειγμάτων (n=80). Αποτελέσματα: Από τη μέθοδο Next-Generation Sequencing, ταυτοποιήθηκαν 23 microRNA μεστατιστικά σημαντική διαφορική έκφραση στα μικρά ανευρύσματα κοιλιακής αορτής. Το miR-24 παρουσίασε τη μεγαλύτερη υπερ-έκφραση, κατά 23 φορές (log2FC 4,5, p= 0,024). Για τα μεγάλα ανευρύσματα κοιλιακής αορτής, συγκριτικά με τα δείγματα ελέγχου καθώς και για τα μικρά συγκριτικά με τα μεγάλα ανευρύσματα, ταυτοποιήθηκαν 33 και 131 microRNA αντίστοιχα, με στατιστικά σημαντική διαφορική έκφραση. Σε περαιτέρω ανάλυση, ανευρέθηκαν 17 microRNA τα οποία ήταν κοινά στις συγκρίσεις της διαφορικής έκφρασης ανάμεσα στις 3 ομάδες: miR-3194 miR-3195, miR-7846, miR-486-2, miR-3178, miR-1538, miR-5589, miR-1908, miR-6504, miR-3159,miR-4771-1, miR-5695, miR-6823, miR-496, miR-193a, miR-7853 και miR-23a. Στο στάδιο της επαλήθευσης με Real – time PCR, αναδείχθηκε μειωμένη έκφραση του miR-24 στο πλάσμα ασθενών με ανευρύσματα κοιλιακής αορτής (μικρά και μεγάλα) συγκριτικά με υγιείς εθελοντές: 0.27 fold-change (p= 0,015) για τα μικρά και 0.15 (p=0,005) για τα μεγάλα ανευρύσματα. Τέλος, δεν ανευρέθηκε συσχέτιση μεταξύ των τιμών Ct από τη Real – Time PCR και τη διάμετρο του ανευρύσματος ή την ηλικία των ασθενών. Συμπέρασμα: Τα ευρήματα της παρούσας μελέτης αναδεικνύουν τη σημαντικότητα του miR-24ως πιθανό βιοδείκτη για τη διάγνωση των μικρών ανευρυσμάτων κοιλιακής αορτής αλλά και ως πιθανό θεραπευτικό στόχο. Περαιτέρω ανάλυση και ταυτοποίηση περισσότερων microRNA, ειδικών για την ανευρυσματική νόσο, είναι καίριας σημασίας για τη διαφοροποίηση μεταξύ παθολογιών με παρόμοιους παθογενετικούς μηχανισμούς.
Ex vivo precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases
Authors: Perocheau Dany , Gurung Sonam , Touramanidou Loukia , Duff Claire , Sharma Garima , Sebire Neil , Finn Patrick F , Cavedon Alex , Siddiqui Summar , Rice Lisa , Martini Paolo G.V. , Frassetto Andrea , Baruteau Julien
Published: April 2024

Background In academic research and the pharmaceutical industry, in vitro cell lines and in vivo animal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have intrinsic limitations, whilst the use of precision-cut tissue slices can bridge the gap between these mainstream models. Precision-cut tissue slices combine the advantage of high reproducibility, studying all cell sub-types whilst preserving the tissue matrix and extracellular architecture, thereby closely mimicking a mini-organ. This approach can be used to replicate the biological phenotype of liver monogenic diseases using mouse models. Methods Here, we describe an optimised and easy-to-implement protocol for the culture of sections from mouse livers, enabling its use as a reliable ex-vivo model to assess the therapeutic screening of inherited metabolic diseases Results We show that precision-cut liver sections can be a reliable model for recapitulating the biological phenotype of inherited metabolic diseases, exemplified by common urea cycle defects such as citrullinemia type 1 and argininosuccinic aciduria, caused by argininosuccinic synthase (ASS1) and argininosuccinic lyase (ASL) deficiencies respectively. Conclusions Therapeutic response to gene therapy such as messenger RNA replacement delivered via lipid nanoparticles can be monitored, demonstrating that precision-cut liver sections can be used as a preclinical screening tool to assess therapeutic response and toxicity in monogenic liver diseases.
Case Report: Leathery black plaque on the temple and scalp
Authors: Rusia Kaveri , Madke Bhushan , Meghe Soham , Kashikar Yash
Published: April 2024

Background Epidermal nevus sebaceous, commonly known as the nevus sebaceous of Jadassohn, is a congenital sebaceous hamartoma. It typically manifests as a single yellowish plaque across the head and neck and is composed of sebaceous glands. It commonly occurs during infancy and grows during puberty. Usually, it follows a benign course; however, in a few cases, it can be malignant. This is the case of a 13-year-old child with verrucous plaques on the temple and scalp. Case report We report the case of a 13-year-old boy with a steadily developing hyperpigmented verrucous plaque on the scalp and ipsilateral side of his face. A dermoscopic examination revealed ridges and fissures in a cerebriform pattern with yellowish-gray globules and a papillary appearance. Physical examination and laboratory tests revealed no abnormalities. Biopsies were taken from the scalp and temple area, and the findings were consistent with the diagnosis of nevus sebaceous. The patient was referred to a plastic surgeon for a staged excision. Conclusions We describe a unique example of a sebaceous nevus that affected the scalp and ipsilateral side of the face. As this hamartomatous growth carries the risk of cancer development, a dermatologist must identify the condition and begin treatment before malignant transformation occurs. This example of multiple verrucous plaques is an exception.
The Beginnings of the Development of Ophthalmology in Slovakia Region Bratislava
Authors: Furdova Alena , Olah Zoltan
Published: April 2024

The first hospital was founded in Bratislava in the territory of today’s Slovakia, but probably also in the whole of Hungary, already in 1307. One of the very serious disease states, threatening the eyes with blindness, was an infectious eye disease – trachoma. According to preserved historical sources, the large spread of trachoma in the territory of Slovakia occurred during the Turkish wars. A fundamental and extremely important moment for ophthalmology was the construction and opening of the new landscape “State” Hospital in Bratislava in the years 1857-1864 (still within Austria-Hungary). The landscape “State” Hospital was built and equipped very modernly for the given period. The fact that among its first “founding” departments: internal, skin-genital, surgical-obstetrical, psychiatric was also ophthalmic department is extremely important, because this made Bratislava one of the first cities in Europe to have a separate inpatient unit for the treatment of eye diseases. Dr. Kanka in 1882-1892 was also the director of the landscape “State” Hospital, as a royal councilor in Bratislava, he also served as regional ophthalmologist and was awarded the 3rd degree of the Iron Crown. Scientifically he dealt with the problems of accommodation of the eye, operating instruments and eye operations, the effect of poisonous substances on the eyes, but also general problems of health care in Bratislava and in some counties of Hungary. Dr. Kanka was among the doctors who were also very active in publishing. The landscape “State” Hospital in Bratislava, which at the time of its foundation was the largest not only in Upper Hungary, but in Hungary as a whole, became, together with the activities of the “Medical and Natural Science Society” in Bratislava, a center of intensive medical-professional and scientific life.
Rewolucja o odroczonej konkluzji. Rewolucje społeczne w perspektywie reform zdrowia publicznego ze szczególnym uwzględnieniem polskiej rewolucji „Solidarności” 1980-1981
Authors: Początek Michał
Published: April 2024

W niniejszym artykule, na podstawie przeglądu prasy partyjnej i związkowej oraz komunikatów podawanych w oficjalnych biuletynach, podjęto próbę oceny istotności zamiarów reformatorskich względem systemu ochrony zdrowia w Polsce w trakcie przemian politycznych na przełomie lat 1980 i 1981. Analiza stanowisk stron podczas eskalacji konfliktu, który dał początek procesom określanym w późniejszej publicystyce mianem pokojowej rewolucji, wskazuje, że nie zarysowano wtedy pomysłu na rzeczywistą przebudowę organizacji i działań służby zdrowia. Protestującym chodziło raczej o doraźne zaspokojenie podstawowych potrzeb wizerunkowych i materialnych tej grupy zawodowej. Trudno orzec, czy dowartościowanie jednej ze stron mogło prowadzić ku prawdziwym reformom, związanym wszakże z koniecznością demokratyzacji systemu politycznego i wprowadzeniem w gospodarce (dotąd socjalistycznej) zasad rynkowych. Konkluzje w postaci rzeczywistej transformacji nastąpiły dopiero po zakończeniu obrad Okrągłego Stołu w 1989 r.