bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal TCF7L2 in Lateral Habenula Is Involved in Stress-Induced Depression
Authors: Li Xincheng , Liu Xiaoyu , Liu Jiaxin , Zhou Fei , Li Yunluo , Zhao Ye , Yin Xueyong , Shi Yun , Shi Haishui
Published: November 2024

Depression is a complex psychiatric disorder that has substantial implications for public health. The lateral habenula (LHb), a vital brain structure involved in mood regulation, and the N-methyl-D-aspartate receptor (NMDAR) within this structure are known to be associated with depressive behaviors. Recent research has identified transcription factor 7-like 2 (TCF7L2) as a crucial transcription factor in the Wnt signaling pathway, influencing diverse neuropsychiatric processes. In this study, we explore the role of TCF7L2 in the LHb and its effect on depressive-like behaviors in mice. By using behavioral tests, AAV-mediated gene knockdown or overexpression, and pharmacological interventions, we investigated the effects of alterations in TCF7L2 expression in the LHb. Our results indicate that TCF7L2 expression is reduced in neurons within the LHb of male ICR mice exposed to chronic mild stress (CMS), and neuron-specific knockdown of TCF7L2 in LHb neurons leads to notable antidepressant activity, as evidenced by reduced immobility time in the tail suspension test (TST) and forced swimming test (FST). Conversely, the overexpression of TCF7L2 in LHb neurons induces depressive behaviors. Furthermore, the administration of the NMDAR agonist NMDA reversed the antidepressant activity of TCF7L2 knockdown, and the NMDAR antagonist memantine alleviated the depressive behaviors induced by TCF7L2 overexpression, indicating the involvement of NMDAR. These findings offer novel insights into the molecular mechanisms of depression, highlighting the potential of TCF7L2 as both a biomarker and a therapeutic target for depression. Exploring the relationship between TCF7L2 signaling and LHb function may lead to innovative therapeutic approaches for alleviating depressive symptoms.
Interleukin-6: Cardiovascular Aspects of Long-Term Cytokine Suppression in Patients with Rheumatoid Arthritis
Authors: Gerasimova Elena V. , Popkova Tatiana V. , Kirillova Irina G. , Gerasimova Daria A. , Nasonov Evgenii L. , Lila Aleksandr M.
Published: November 2024

In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index (p < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, p = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, p = 0.03) in RA patients receiving statins. Initially, the thickness of the intima–media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; p < 0.01), BMI (R = 0.37; p < 0.01), and systolic blood pressure (R = 0.64; p < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; p < 0.01) and LDL-C (R = 0.33; p < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = −0.25, p = 0.01) and at the end of this study (R = 0.29, p < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy.
Phosphoproteomics: Advances in Research on Cadmium-Exposed Plants
Authors: Marques Deyvid Novaes , Piotto Fernando Angelo , Azevedo Ricardo Antunes
Published: November 2024

With the increasing concern on heavy metal contamination in agriculture and other environmental settings, unraveling the mechanisms of cadmium (Cd) tolerance and response in plants has become highly important. Ongoing plant Cd research over the years has focused on strategic and relevant aspects, including molecular, biochemical, and physiological processes. From this perspective, phosphoproteomics appears to be an innovative and powerful approach to investigating plant responses to Cd stress. Here, we summarize progress in plant Cd research across different plant species regarding large-scale phosphoproteomic investigations. Some studies revealed major proteins participating in detoxification, stress signaling, and metabolism, along with their regulation through phosphorylation, which modulates the plant’s defense against Cd. However, many pathways remain unexplored. Expanding these studies will help our ability to alleviate Cd stress and provide further information concerning involved mechanisms. Our purpose is to inspire researchers to further explore the use of phosphoproteomics in unraveling such complex mechanisms of Cd tolerance and response across various plant species, with the ultimate aim of enhancing strategies for mitigating Cd stress in agriculture and polluted environments.
Comparative Analysis of Mesocotyl Elongation Ability among Maize Inbred Lines
Authors: Wen Daxing , Tian Xiaoyu , Wu Chenglai , Zhang Chunqing
Published: November 2024

Mesocotyl plays a key role in the seedling emergence of maize; however, the mechanism of mesocotyl elongation is still unclear. Moreover, different maize inbred lines and cultivars have varied mesocotyl lengths positively correlated with deep sowing tolerance. In this study, we selected one inbred line with long mesocotyl (LM) and two maize inbred lines with short mesocotyl (SM1 and SM2) from more than 400 maize inbred lines. The mesocotyl length of the LM line was about three-fold longer than those of the SM1 and SM2 lines. Microstructure observation showed that the reason for short mesocotyl in the SM1 and SM2 lines was few cell numbers and short cell length, respectively. Subsequently, we used RNA-seq to investigate the mechanism of mesocotyl elongation by regulating cell number and cell length at the transcriptome level. Compared with the LM line, the SM1 line displayed stronger downregulation of Cytochrome P450 and peroxidase genes than the SM2 line. Moreover, plant hormone signal transduction plays a vital role in mesocotyl elongation. Taken together, we propose a model for mesocotyl elongation of maize inbred lines with different cell lengths and cell numbers, which provide new insights into mesocotyl elongation in maize.
Drug Repurposing for Cancer Treatment: A Comprehensive Review
Authors: Al Khzem Abdulaziz H. , Gomaa Mohamed S. , Alturki Mansour S. , Tawfeeq Nada , Sarafroz Mohammad , Alonaizi Shareefa M. , Al Faran Alhassan , Alrumaihi Laela Ahmed , Alansari Fatimah Ahmed , Alghamdi Abdullah Abbas
Published: November 2024

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therapeutic area where drug repurposing has shown the most prominent impact. This review presents a compilation of medications that have been repurposed for the treatment of various types of cancers. It describes the initial therapeutic and pharmacological classes of the repurposed drugs and their new applications and mechanisms of action in cancer treatment. The review reports on drugs from various pharmacological classes that have been successfully repurposed for cancer treatment, including approved ones and those in clinical trials and preclinical development. It stratifies drugs based on their anticancer repurpose as multi-type, type-specific, and mechanism-directed, and according to their pharmacological classes. The review also reflects on the future potential that drug repurposing has in the clinical development of novel anticancer therapies.
Strength Characteristics of DMJ Piles Based on Indoor Tests
Authors: Yue Hongzhi , Zhang Yuhe , Rong Yu , Feng Weizhe , Wang Yang , Zhao Lin , Wang Songtao , Ding Ruosong , Yang Fan , Yao Zhanyong , Yao Kai
Published: November 2024

The Deep Cement Mixing Integrated Drilling, Mixing and Jetting (DMJ) method represents a novel approach to the construction of slurry piles in the Yellow River Floodplain, offering the potential to enhance the quality of these structures. In order to investigate the pile strength and its distribution characteristics under different conditions, an unconfined compressive strength test was conducted on DMJ pile core samples. The Kolmogorov-Smirnov (K-S) test was employed to evaluate the normal distribution characteristics of the strength, and the fluctuation of the pile strength was evaluated by the autocorrelation function method to elucidate the distribution characteristics. Moreover, a resistivity non-destructive test was conducted to ascertain the correlation between strength and resistivity and to perform supplementary strength testing. The distribution of the pile body strength is normal at the 5% level of significance. A clear correlation was observed between the strength of the pile core and depth, while the correlation between the strength of the pile outer side and depth was less pronounced. Additionally, a positive linear correlation was observed between resistivity and strength, which can be used to evaluate the strength of DMJ piles.
Midseptal and Anteroseptal Accessory Pathway Ablation in Children
Authors: Környei László , Jan Matevž , Ebrahim Mohammad , Radeljić Vjekoslav , Rode Mirta , Delić-Brkljačić Diana , Kralik Ivana , Kocsis Flóra , Krmek Nikola
Published: November 2024

Objectives: The goal of this study is to document outcomes of ablation for high-risk accessory pathways in paediatrics using 3D mapping systems with minimal to zero fluoroscopy. Methods: It is a cross-sectional, multicentre study, conducted between 2013 and 2023, and involving four different centres in Hungary, Croatia, Kuwait, and Slovenia. Results: A total of 128 procedures were performed on 111 patients. The cohort included 57.8% anteroseptal (AS) pathways and 42.2% midseptal (MS) pathways. The mean follow-up time was 2.0 ± 2.1 years. Cryoablation was used in 72.7% of the cases, and radiofrequency ablation was used in 27.3%. The EnSite Precision™ Cardiac Mapping System was the predominant system used. The overall acute success rate was 89.1%, with recurrence rates at 17.2% with similar results regardless of the type of energy used. The success rate was not significantly different between AS and MS substrates. The age and weight of the patient had no bearing on the outcomes (median age and weight were 13 years and 52 kg, respectively). The complications rate was at 4.69% and included transient AV block (three patients), hematoma (one patient), right bundle branch block (one patient), and possible permanent complete AV block (one patient). Fluoroscopy was utilized in 18 cases, with a fluoroscopy time mean of 3 min and 45 s. Conclusions: MS and AS AP in paediatric patients can be treated effectively with either RF or cryoablation and with a low dose of radiation using 3D mapping systems, with excellent acute success rates and low complication rates.
Minimally Invasive Repair of Pectus Excavatum: A Lifeline to Quality of Life
Authors: Higaze Mostafa , Haj Khalaf Mohamed Anwar , Parjiea Chirag , Sirbu Horia
Published: November 2024

Background: Pectus excavatum, a deformity of the chest wall, can lead to significant emotional and social challenges, adversely affecting an individual’s overall well-being. While the Nuss procedure is a well-established treatment, this study evaluates the impact of a modified, minimally invasive approach on patients’ quality of life. Methods: This retrospective study analyzed patients who underwent minimally invasive pectus excavatum repair (MIRPE) from 1 January 2010 to 31 January 2024. Collected data included demographics, operative details, and patient outcomes. Health-related quality of life (HRQoL) was assessed using the SF-36 questionnaire, administered preoperatively and at least four weeks post-surgery. Results: Two hundred thirty-four patients (195 male, mean age 20.5 ± 6 years) underwent MIRPE. Postoperative results showed statistically significant improvements in all dimensions of HRQoL (Physical Component Summary Score (PCS) p = 0.007; Mental Component Summary Score (MCS) p < 0.001). Importantly, postoperative HRQoL scores were not just improved but comparable to those of the general German population, providing reassurance and confidence in the effectiveness of MIRPE. Conclusions: This study demonstrates that MIRPE significantly enhances patients’ quality of life (HRQoL). The improvements observed post-surgery bring HRQoL to levels akin to healthy individuals in the German population. These findings underscore the profound positive impact of MIRPE on patients’ well-being, offering hope and optimism for the future of pectus excavatum treatment.
7-Year Follow-Up of Maxillary Overdentures Supported by Mini-Dental Implants
Authors: Van Doorne Luc , Demeulenaere Laure , Dejans Marie , De Bruyn Hugo
Published: November 2024

Background: Mini dental implants (MDIs) are alternatives to support an overdenture when a standard diameter implant cannot be placed due to lack of bone volume. They reduce the need for invasive bone grafting and lower the barrier for treatment. Aim: This prospective study reports on implant and patient-centered outcomes of flaplessly placed, early loaded MDIs supporting horseshoe-shaped maxillary overdentures after 7 years of function. Materials and Methods: Patients with a CBCT-confirmed thin alveolar crest received 5–6 one-piece MDIs using mentally guided flapless surgery. The conventional denture was relined and MDIs were provisionally loaded within one week. After 6 months the non-splinted MDIs were actively loaded with a horseshoe overdenture. Implant and prosthetic survival, peri-implant health (PPD and BoP) and patient-related outcomes using OHIP-14 and Subjective Masticatory Evaluation were assessed after 7 years. Results: 185 MDIs were placed in 14 females and 17 males. During provisional loading, 32 MDIs were lost, and 17 replacements were required in 16 patients. In total, 170 out of 202 totally placed MDIs were supporting 29 overdentures after 6 months. Cumulative implant failure increased from 15.8% at the moment of active loading to 34.7% at 7 years. After 7 years, 76% of the initially placed overdentures remained functional, mean PPD was 3.48 (SD 0.86), BoP was 0.20 (SD 0.40) and peri-implantitis incidence was 0.9%. The total OHIP-14 was reduced from 21.3/56 (SD: 13.1) preoperatively to 15.6/56 (SD 12.8) at provisional loading (p > 0.1) and 7.3/56 (SD 6.7) at final loading (p = 0.006), and it remained unchanged up to 7 years at 6.57/56 (SD: 8.92) (p > 0.5). Conclusions: Maxillary MDIs provide an acceptable treatment option in patients with deficient bone volume that cannot or refuse to be treated with bone grafting. Despite one third of the MDIs being lost, remaining MDIs had good peri-implant health, prosthetic success was 71% and Oral Health Related Quality of Life was beyond expectations.
The Influence of Kinematic Alignment on Patellofemoral Joint Biomechanics in Total Knee Arthroplasty
Authors: Simon Johanna-Maria , Bauer Leandra , Thorwächter Christoph , Woiczinski Matthias , Simon Florian , Müller Peter E. , Holzapfel Boris M. , Niethammer Thomas R.
Published: November 2024

Background: Anterior knee pain is a prevalent issue post total knee arthroplasty, often necessitating revision surgery. Various factors contribute to this complication, including patellar maltracking and excessive patellofemoral load. Kinematic alignment has emerged as an alternative, showing promising outcomes in clinical studies. However, its impact on patellofemoral biomechanics needs to be more adequately understood. This study compared the effects of kinematically versus mechanically aligned total knee arthroplasty on patellofemoral joint biomechanics. Methods: Eight fresh-frozen human knee specimens underwent biomechanical testing in a knee rig setup, performing an active weight-loaded knee joint flexion of 30–130°. After the testing of native kinematics, kinematically and mechanically aligned total knee arthroplasty was performed using a medial pivot implant design without patellar resurfacing. Quadriceps force, retropatellar peak pressure and the retropatellar contact area were measured during knee flexion using a patellar pressure-sensitive film. Patella kinematics (shift and tilt) was tracked using an optoelectrical measurement system. Functional regressions were used to determine the influence of the alignment on the kinematics and loading of the knee joint. Results: Kinematically aligned total knee arthroplasty resulted in reduced quadriceps force during knee flexion compared to mechanically aligned total knee arthroplasty. Retropatellar peak pressure, retropatellar contact area and patella kinematics did not vary between the alignments. Conclusions: Kinematic alignment offers potential benefits in reducing quadriceps force during knee flexion, which may mitigate anterior knee pain risk. Further research is needed to elucidate its effects in varying anatomical conditions and alignment strategies.
The Usefulness of Carotid Artery Doppler Measurement as a Predictor of Early Death in Sepsis Patients Admitted to the Emergency Department
Authors: Kim Su-Il , Jang Yun-Deok , Ji Jae-Gu , Kim Yong-Seok , Kang In-Hye , Kim Seong-Ju , Han Seong-Min , Choi Min-Seok
Published: November 2024

Background: This study aims to verify whether the blood flow velocity and the diameter size, measured through intra-carotid artery Doppler measurements performed on sepsis patients visiting the emergency department, are useful as tools for predicting the risk of early death. Methods: As a prospective study, this research was performed on sepsis patients who visited a local emergency medical center from August 2021 to February 2023. The sepsis patients’ carotid artery was measured using Doppler imaging, and they were divided into patients measured for the size of systolic and diastolic mean blood flow velocity and diameter size: those measured for their qSOFA (quick sequential organ failure assessment) score and those measured using the SIRS (systemic inflammatory response syndrome) criteria. By measuring and comparing their mortality prediction accuracies, this study sought to verify the usefulness of blood flow velocity and the diameter size of the intra-carotid artery as tools to predict early death. Results: This study was conducted on 1026 patients, excluding 45 patients out of the total of 1071 patients. All sepsis patients were measured using systolic and diastolic blood flow velocity and diameter by Doppler imaging of the intra-carotid artery, assessed using qSOFA and evaluated using SIRS criteria. The results of the analysis performed to compare the mortality prediction accuracy were as follows. First, the hazard ratio (95% CI) of the intra-carotid artery was significant (p < 0.05), at 1.020 (1.004–1.036); the hazard ratio (95% CI) of qSOFA was significant (p < 0.05), at 3.871 (2.526–5.931); and the hazard ratio (95% CI) of SIRS showed no significant difference, at 1.002 (0.995–1.009). After 2 h of infusion treatment, the diameter size was 4.72 ± 1.23, showing a significant difference (p < 0.05). After 2 h of fluid treatment, the blood flow velocity was 101 m/s ± 21.12, which showed a significant difference (p < 0.05). Conclusions: Measuring the mean blood flow velocity in the intra-carotid arteries of sepsis patients who visit the emergency department is useful for predicting the risk of death at an early stage. And this study showed that Doppler measurement of the diameter size of the carotid artery significantly increased after performing fluid treatment after early recognition.
An Additional Certification as a Centre for Geriatric Trauma Had No Benefit on Mortality Among Seriously Injured Elderly Patients—An Analysis of the TraumaRegister DGU® with Data of the Registry for Geriatric Trauma (ATR-DGU)
Authors: Pass Bastian , Aigner Rene , Lefering Rolf , Lendemans Sven , Hussmann Bjoern , Maek Teresa , Bieler Dan , Bliemel Christopher , Neuerburg Carl , Schoeneberg Carsten ,   the TraumaRegister DGU
Published: November 2024

Background/Objectives: The number of seriously injured elderly patients is continuously rising. Several studies have underlined the benefit of orthogeriatric co-management in treating older patients with a proximal femur fracture. The basis of this orthogeriatric co-management is a certification as a Centre for Geriatric Trauma (ATZ). Data of seriously injured patients are collected in the TraumaRegister DGU® (TR-DGU) from participating trauma centres. We hypothesise that if a certified trauma centre is also a certified Centre for Geriatric Trauma, a benefit can be measured. Methods: Retrospective cohort analysis was conducted from 1 January 2016 to 31 December 2021. The TraumaRegister DGU® collected the data prospectively. This retrospective multicentre registry study included patients 70 years or older with an abbreviated injury scale of ≥3 and intensive care unit treatment from 700 certified Trauma Centres and 110 Centres for Geriatric Trauma in Germany, Austria and Switzerland. The primary outcome was mortality in in-hospital stays. Other outcome parameters were days of intubation, the length of stay in ICU, and in-hospital stays. Furthermore, the discharge target and the Glasgow Outcome Scale (GOS) were analysed. Results: The inclusion criteria were met by 27,531 patients. The majority of seriously injured patients (n = 23,007) were transported to certified trauma centres without certification as ATZ. A total of 4524 patients were transported to a trauma centre with additional ATZ certifications. Mortality and the Revised Injury Severity Classification II (RISC-II) model for prediction of mortality after trauma were higher in ATZ hospitals. Logistic regression analysis showed no effect on mortality by a certification as a centre for geriatric trauma in treating seriously injured elderly patients. Conclusions: We assume that the additional ATZ certification does not positively influence the treatment of seriously injured elderly patients. A potential side effect could not be measured.
The Role of Positron Emission Tomography/Computed Tomography in the Management of Differentiated Thyroid Cancer: Current Applications and Future Perspectives
Authors: Panagiotidis Emmanouil , Zhang-Yin Jules Tianyu
Published: November 2024

Differentiated thyroid cancer (DTC), comprising papillary and follicular thyroid carcinoma, is the most common thyroid malignancy and typically has a favourable prognosis when detected early. Positron emission tomography/computed tomography (PET/CT) has emerged as a valuable imaging modality, integrating metabolic and anatomical data. Although PET/CT is not usually part of the initial diagnostic process due to DTC’s indolent nature and low metabolic activity, it plays an essential role in selected clinical scenarios. This includes identifying recurrence in patients with elevated thyroglobulin (Tg) levels and negative radioactive iodine (RAI) scans, evaluating metastatic disease, and guiding treatment in advanced cases. As the use of PET/CT evolves in oncology, this review explores its application in regard to staging, detection of recurrence, and follow-up in terms of managing DTC while also evaluating potential challenges that may occur in the future. The review also considers emerging radiotracers and the theragnostic potential of PET/CT.
Management of Pediatric Mandibular Condyle Fractures: A Literature Review
Authors: Bottini Gian Battista , Roccia Fabio , Sobrero Federica
Published: November 2024

This narrative review evaluates the literature on the management of mandibular condyle fractures in growing patients. It aims to illustrate some fundamental biological principles and to offer a series of considerations applicable to clinical practice. The discussion is based on 116 papers published in PubMed and two relevant textbooks. Condylar fractures may be overlooked, especially in pre-scholar children, where compliance is usually reduced. However, these injuries can have disabling sequelae such as ankyloses, facial deformities, malocclusion, and chronic pain in some patients if not diagnosed and managed correctly. Due to their significance, mandibular condyle fractures in children are a subject of considerable clinical interest. As of today, there is consensus about their treatment. Four management options are available: expectative (analgesia, soft food and follow-up), functional protocols (guiding elastics, orthodontic appliances and exercises), maxillomandibular fixation (MMF), and open reduction and internal fixation (ORIF). Nondisplaced and minimally displaced fractures should be treated expectantly; severely displaced non-comminuted fractures can be safely operated on if the expertise is available, even in patients with deciduous dentition. Moderately displaced fractures can be managed with functional protocols or operatively, depending on the background and know-how of the specialist. Functional protocols can achieve good outcomes, especially in patients with deciduous dentition. MMF should be foregone in children due to its many drawbacks.
Predicting Syndromic Status Based on Longitudinal Data from Parental Reports of the Presence of Additional Structural and Functional Anomalies in Children Born with an Orofacial Cleft
Authors: Davies Amy J. V. , Wren Yvonne E. , Hamilton Mark , Sandy Jonathan R. , Stergiakouli Evangelia , Lewis Sarah J.
Published: November 2024

Background: Orofacial clefts are the most common craniofacial congenital malformation in humans. Approximately 30% of clefts arise as part of a syndrome or sequence, characterised by co-existing structural and functional anomalies. Many syndromes are thought to be undiagnosed, although the presence of multiple anomalies may indicate the presence of a syndrome or sequence. Aim: To determine the extent to which the presence of additional structural and functional anomalies can help to identify those children with an undiagnosed syndrome. Methods: Secondary data analysis was performed using data from 1701 children born with an orofacial cleft, collected as part of a longitudinal cohort study, the Cleft Collective. Data were collected between 2013 and 2023 across the United Kingdom. The prevalence of structural and functional anomalies and syndromes were explored using descriptive statistics. Logistic regression was used to determine the extent to which anomalies can predict syndromic status. Results: A syndrome and/or sequence was reported in 20.5% children. Among children who reported five or more anomalies, the prevalence of a diagnosed syndrome was 81.5%. When adjusting for cleft subtype and sex, in 27 out of 32 anomalies tested, strong evidence was found to suggest increased odds of having a syndrome if the specific anomaly was present compared to if the anomaly was absent (p-values ranged between 1.4 × 10−30 and 0.002). Conclusions: Children born with a cleft who present with two or more anomalies are much more likely to have a syndrome than those with fewer anomalies and should be prioritised for genetic screening and counselling.
MicroRNA-133a and MicroRNA-145 May Be Involved in the Development of Hypertension-Mediated Organ Damage in Children with Primary Hypertension—A Preliminary Study
Authors: Szyszka Michał , Skrzypczyk Piotr
Published: November 2024

Background/Objectives: Studies in adults have demonstrated the essential role of microRNAs in developing hypertension and their effect on hypertension sequelae. In this preliminary study, we aimed to investigate the expression of five miRNA particles, miRNA-21, miRNA-27a, miRNA-27b, miRNA-133a, and miRNA-145, in school-aged children with primary hypertension and to examine their correlations with blood pressure and arterial and heart properties. Methods: In 22 hypertensive children (15.1 ± 1.9 years), we measured blood pressure parameters (office, central, and 24 h), the urinary albumin/creatinine ratio, and the pulse wave velocity (PWV) before and after one hour of aerobic exercise. The left ventricular mass index (LVMI) and common carotid artery intima–media thickness (cIMT) were also assessed. The relative miRNA expression was calculated using the 2−ΔΔCt method with miRNA-16 as an endogenous control and the pre-exercise miRNA expression levels as the control (baseline). Results: We found a statistically significant decrease in both the office and 24 h ambulatory diastolic blood pressure after 1 h of exercise (82.2 ± 8.5 mm Hg versus 78.6 ± 8.8 mm Hg, p = 0.01 and 75.0 ± 8.3 mm Hg versus 73.0 ± 7.4 mm Hg, p = 0.02). The increase in miRNA-133a expression after exercise correlated positively with the LVMI. Furthermore, the rise in miRNA-145 expression after exercise correlated negatively with the systolic and diastolic office and 24 h blood pressure and with markers of arterial damage: 24 h PWV and cIMT. Conclusions: In conclusion, miRNA-133a may be a biomarker of left ventricular hypertrophy in children with elevated blood pressure. Additionally, changes in miRNA-145 expression induced by exercise might reduce the blood pressure after exercise and protect against arterial damage. Both miRNA-133a and miRNA-145 may be involved in epigenetic alterations in children affected by primary hypertension that may contribute to the exacerbation of HMOD.
Celiac Disease and Inflammatory Cardiomyopathies: Exploring the Heart-Gut Axis
Authors: Birtolo Lucia Ilaria , Di Pietro Gianluca , Improta Riccardo , Severino Paolo , Shahini Endrit , Vizza Carmine Dario
Published: November 2024

Background: Celiac disease (CD) is associated with an increased risk of cardiovascular (CV) events, especially inflammatory heart diseases. We aimed to gather evidence on the association between CD and inflammatory CV diseases, including pericarditis and myocarditis, and the underlying pathophysiological mechanisms. Methods: The PubMed, Scopus, and Google Scholar databases were searched for studies assessing the prevalence and the long-term outcomes of patients with CD and inflammatory CV diseases. Result: Ten studies (nine case series/reports and one prospective observational study) covering a total of 22 patients, including 9 women (41%) and 13 men (59%), were evaluated. The median age was 23 (IQR, 12–41) years. A total of 6 patients had recurrent pericarditis, while 16 patients had celiac-related myocarditis (11 patients presented with heart failure and 5 with arrhythmia). A strict gluten-free diet (GFD) alone was effective in 87.5% of cases (4/6 for pericarditis and 10/16 for myocarditis). All patients with pericarditis achieved complete resolution of symptoms. Conversely, heart function was restored in 81% of patients with myocarditis. Only one patient died. Conclusions: Myocarditis and/or pericarditis, especially if recurrent, may complicate CD in pediatric and adult subjects due to an autoimmune reaction involving the pericardium/myocardium and the small intestine.
The Effectiveness of Thermal Stimulation Plus Conventional Therapy for Functional Recovery After Stroke: A Systematic Review and Meta-Analysis
Authors: Celi-Lalama Daniela , Soria-Vizcaino Aida , Flores-Santy Lucía Fernanda , Araya-Quintanilla Felipe , Esparza Wilmer Danilo , Cuyul-Vásquez Iván , Gutiérrez-Espinoza Héctor
Published: November 2024

Background: Motor impairments limit the functional abilities of patients after stroke; it is important to identify low-cost rehabilitation avenues. The aim of this study is to determine the effectiveness of thermal stimulation in addition to conventional therapy for functional recovery in post-stroke patients. Methods: An electronic search was performed in the MEDLINE, Scopus, Web of Science, EMBASE, CINAHL, SPORTDiscus, Epistemonikos, LILACS, and PEDro databases. The eligibility criterion was randomized clinical trials that analyzed the clinical effects of thermal stimulation plus conventional therapy. Two authors independently performed the search, study selection, data extraction, and risk of bias assessment. Results: Eight studies met the eligibility criteria, and six studies were included in the quantitative synthesis. For thermal stimulation plus conventional therapy versus conventional therapy alone, the mean difference (MD) for function was 6.92 points (95% CI = 4.36–9.48; p < 0.01), for motor function was 6.31 points (95% CI = 5.18–7.44; p < 0.01), for balance was 4.41 points (95% CI = −2.59–11.4; p = 0.22), and for walking was 1.01 points (95% CI = 0.33–1.69; p < 0.01). For noxious thermal stimulation versus innocuous thermal stimulation, the MD for activities of daily living was 1.19 points (95% CI = −0.46–2.84; p = 0.16). Conclusions: In the short term, adding thermal stimulation to conventional therapy showed statistically significant differences in functional recovery in post-stroke patients. The quality of evidence was high to very low according to GRADE rating. The studies included varied in the frequency and dosage of thermal stimulation, which may affect the consistency and generalizability of the results. A larger quantity and a better quality of clinical studies are needed to confirm our findings. PROSPERO registration: CRD42023423207.
Denervation of the Patella During Knee Arthroplasty: An Updated Systematic Global Review
Authors: Nkachukwu Kennedy , Alejo Amanda , Toman Jeffrey , Jwayyed Jalal , Iwuagwu Justin , Alejo Andrew
Published: November 2024

Background: Total knee arthroplasty is a widely endorsed surgical intervention, extensively recognized within the orthopedic field for its efficacy in significantly reducing pain and enhancing overall mobility in patients suffering from advanced stages of osteoarthritis. Despite a general consensus on the core procedural steps, the rapid advancements in implant technology and the nuanced techniques in knee reconstruction have inevitably introduced subtle variations in surgical approaches. These variations often emerge due to individual surgeon preferences, their unique expertise, and comfort levels with specific techniques. Anterior knee pain, however, remains a frequent postoperative complication, likely attributed to the extensive and complex innervation of the patella. To address this challenge, some surgeons have adopted patellar denervation, hypothesizing that by reducing nerve signaling from the patellar region, patients may experience a measurable decrease in pain. Methods: A systematic search was performed to include eight recent level I studies to analyze this issue. Results: Of the eight reviews, there were four strong studies that concluded patellar denervation helps decrease anterior knee pain in the acute period, but this may not last long term. The other four papers did not show a difference in anterior knee pain after denervation. Conclusions: This review synthesizes and critically analyzes the current body of literature, aiming to provide clinicians with evidence-based insights into the potential benefits and limitations of incorporating patellar denervation into their surgical especially during the acute post-operative period.
Endoscopic Local Excision (ELE) with Knife-Assisted Resection (KAR) Techniques Followed by Adjuvant Radiotherapy and/or Chemotherapy for Invasive (T1bsm2,3/T2) Early Rectal Cancer: A Multicenter Retrospective Cohort
Authors: Tribonias George , Papaefthymiou Apostolis , Zormpas Petros , Seewald Stefan , Zachou Maria , Barbaro Federico , Kahaleh Michel , Andrisani Gianluca , Elkholy Shaimaa , El-Sherbiny Mohamed , Komeda Yoriaki , Yarlagadda Raghavendra , Tziatzios Georgios , Essam Kareem , Haggag Hany , Paspatis Gregorios , Mavrogenis Georgios
Published: November 2024

Background: Resected rectal polyps with deep invasion into the submucosa (pT1b-sm2,3) or the muscle layer (pT2) are currently confronted with surgery due to non-curative resection. Aims: We evaluated the efficacy, safety, and locoregional control of adjuvant radiotherapy (RT) and/or chemotherapy (CT) following endoscopic KAR (knife-assisted resection) in patients with invasive early rectal cancers who are unwilling or unsuitable for additional surgical resection. Methods: Fifty-one patients with early rectal cancers, pT1b or pT2, underwent post-resection adjuvant RT and/or CT in 15 centers worldwide. “En bloc” macroscopic resection, R0 resection, recurrence rate, and adverse events following resection and adjuvant therapy were recorded in a multicenter retrospective cohort study. Results: Diagnostic staging (38/51, 75%) was the main reason for ELE. Macroscopic “en bloc” resection was demonstrated in 50/51 (98%), with an average follow-up of 20.6 months. Endoscopic recurrence occurred in 7/51 (13.7%) of patients, with mean time for diagnosis of recurrence at 8.9 months. Adjuvant therapy consisted of RT in 49.0% (25/51), CT in 11.8% (6/51), and combined CRT in 39.2% (20/51) of the cases. Perforation, severe post-procedural bleeding, and incontinence were the most frequent complications. The absence of superficial ulceration was associated with macroscopic complete resection, while the lesions with lower budding stage, clear lateral margins, lesion size < 40 mm, and needle-type knife used were associated with less endoscopic recurrencies. Conclusions: Our data investigated adjuvant RT and/or CT after endoscopic KAR of infiltrative rectal cancers (pT1bsm2,3-pT2) as being safe and effective for locoregional control and providing a non-surgical treatment option for patients with a non-curative resection.
The Association Between Diabetic Nephropathy and Triglyceride/Glucose Index and Triglyceride/High-Density Lipoprotein Cholesterol Ratio in Patients with Type 2 Diabetes Mellitus
Authors: Tam Abbas Ali , Altay Feride Pınar , Demir Pervin , Ozdemir Didem , Topaloglu Oya , Ersoy Reyhan , Cakır Bekir
Published: November 2024

Background: In this study, we aimed to investigate the relationship between diabetic nephropathy (DN) and triglyceride/glucose (TyG) index and triglyceride/high-density lipoprotein cholesterol ratio (Tg/HDL-C) as surrogate markers of insulin resistance. Method: Medical records of 15,378 individuals between February 2019 and May 2024 were examined. Serum glucose, Tg, HDL-C, HbA1c, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio (UACR) were evaluated and the TyG index and TG/HDL-C ratios were calculated for each individual. DN was defined as a UACR ≥ 30 mg/g and/or eGFR <60 mL/min/1.73 m2. Results: Of 10,714 patients, DN was detected in 3763 (35.1%). Females had 10% higher odds of developing DN compared to males. A TyG index at or above the determined cutoff point (9.58) indicated a risk of DN and the sensitivity and specificity values were 44.01% and 71.28%, respectively. The risk of DN was 1.95 times higher in individuals with a TyG index value of ≥9.58 compared to those with a TyG index <9.58. While the Tg/HDL ratio was significant in detecting DN in the univariate analysis (odds ratio (OR) 1.59; 95% confidence interval 1.46–1.73), this significance was not found in the multivariate analysis (OR 1.15; 95% confidence interval 0.94–1.40). Conclusions: A high TyG index is associated with DN in patients with type 2 diabetes and it might be a potential marker in predicting DN.
Liver Dysfunction in a Patient with Graves’ Disease
Authors: Campos Filipa , Sharma Angelica , Patel Bijal , Papadopoulou Deborah , Comninos Alexander N. , Abbara Ali
Published: November 2024

Liver dysfunction can occur in patients presenting with thyrotoxicosis, due to several different aetiologies. A 42-year-old man had mild liver dysfunction on presentation with hyperthyroidism due to Graves’ disease (GD): ALT 65 (0–45 IU/L), fT4 41.2 (9–23 pmol/L), fT3 > 30.7 (2.4–6 pmol/L), and TSH < 0.01 (0.3–4.2 mIU/L). His liver dysfunction worsened following the initiation of the antithyroid drug (ATD) carbimazole (CBZ), with ALT reaching a zenith of 263 IU/L at 8 weeks following presentation. Consequently, CBZ was stopped, and he was managed with urgent radioiodine therapy. His liver function tests (LFTs) improved within 1 week of stopping carbimazole (ALT 74 IU/L). Thionamide-induced liver dysfunction is more typically associated with a ‘cholestatic’ pattern, although he had a ‘hepatitic’ pattern of liver dysfunction. The risk of liver dysfunction in GD increases with older age and higher titres of thyroid-stimulating hormone receptor antibody (TRAb). This review of the literature seeks to explore the possible causes of liver dysfunction in a patient presenting with hyperthyroidism, including thyrotoxicosis-induced liver dysfunction, ATD-related liver dysfunction, and the exacerbation of underlying unrelated liver disease.
VEXAS Syndrome: A Comprehensive Review of Current Therapeutic Strategies and Emerging Treatments
Authors: Alqatari Safi , Alqunais Abdulaziz A. , Alali Shahad M. , Alharbi Mohammed A. , Hasan Manal , Al Shubbar Mohammed D.
Published: November 2024

VEXAS syndrome is a recently identified autoinflammatory disorder resulting from somatic mutations in the UBA1 gene, leading to a complex spectrum of severe inflammatory and hematologic manifestations. The absence of established treatment guidelines and the variability in clinical presentation make its management particularly challenging. Current therapeutic approaches are often based on limited evidence, and their effectiveness remains inconsistent. This review seeks to consolidate the existing knowledge on therapeutic strategies for VEXAS syndrome, offering a critical evaluation of their efficacy and addressing the gaps in the current literature. As the clinical recognition of VEXAS grows, there is an urgent need to explore more targeted, effective treatments that can address both the inflammatory and hematologic aspects of the disease. By providing a comprehensive analysis of the current therapeutic landscape, this review aims to guide clinicians and researchers toward developing more effective, long-term management strategies for this life-threatening condition.
Numerical Analysis on Static Performances of Graphene Platelet-Reinforced Ethylene-Tetrafluoroethylene (ETFE) Composite Membrane Under Wind Loading
Authors: Wang Yu , Gu Jiajun , Zhang Xin , Fan Jian , Ji Wenbin , Feng Chuang
Published: November 2024

This study examines the static performances of a graphene platelet (GPL)-reinforced ethylene tetrafluoroethylene (ETFE) composite membrane under wind loadings. The wind pressure distribution on a periodic tensile membrane unit was analyzed by using CFD simulations, which considered various wind velocities and directions. A one-way fluid–structure interaction (FSI) analysis incorporating geometric nonlinearity was performed in ANSYS to evaluate the static performances of the composite membrane. The novelty of this research lies in the integration of graphene platelets (GPLs) into ETFE membranes to enhance their static performance under wind loading and the combination of micromechanical modelling for obtaining material properties of the composites and finite element simulation for examining structural behaviors, which is not commonly explored in the existing literature. The elastic properties required for the structural analysis were determined using effective medium theory (EMT), while Poisson’s ratio and mass density were evaluated using rule of mixtures. Parametric studies were carried out to explore the effects of a number of influencing factors, including pre-strain, attributes of wind, and GPL reinforcement. It is demonstrated that higher initial strain effectively reduced deformation under wind loads at the cost of increased stress level. The deformation and stress significantly increased with the increase in wind velocity. The deflection and stress level vary with the wind direction, and the maximum values were observed when the wind comes at 15° and 45°, respectively. Introducing GPLs with a larger surface area into membrane material has proven to be an effective way to control membrane deformation, though it also results in a higher stress level, indicating a trade-off between deformation management and stress management.
Ppn2 Polyphosphatase Improves the Ability of S. cerevisiae to Grow in Mild Alkaline Medium
Authors: Eliseeva Irina A. , Ryazanova Lubov , Ledova Larisa , Zvonarev Anton , Valiakhmetov Airat , Suntsova Maria , Modestov Aleksander , Buzdin Anton , Lyabin Dmitry N. , Kulakovskiy Ivan V. , Kulakovskaya Tatiana
Published: November 2024

Inorganic polyphosphates and respective metabolic pathways and enzymes are important factors for yeast active growth in unfavorable conditions. However, particular proteins of polyphosphate metabolism remain poorly explored in this context. Here we report biochemical and transcriptomic characterization of the CRN/PPN2 yeast strain (derived from Ppn1-lacking CRN strain) overexpressing poorly studied Ppn2 polyphosphatase. We showed that Ppn2 overexpression significantly reduced lag phase in the alkaline medium presumably due to the ability of Ppn2 to efficiently hydrolyze inorganic polyphosphates and thus neutralize hydroxide ions in the cell. With RNA-Seq, we compared the molecular phenotypes of CRN/PPN2 and its parent CRN strain grown in YPD or alkaline medium and detected transcriptomic changes induced by Ppn2 overexpression and reflecting the adaptation to alkaline conditions. The core set of upregulated genes included several genes with a previously unknown function. Respective knockout strains (∆ecm8, ∆yol160w, ∆cpp3, ∆ycr099c) exhibited defects of growth or cell morphology in the alkaline medium, proving the functional involvement of the respective proteins in sustaining growth in alkaline conditions.