bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of carglumic acid in the long-term management of propionic and methylmalonic acidurias
Authors: Yap Sufin , Gasperini Serena , Matsumoto Shirou , Feillet François 
Published: December 2024

AbstractPropionic aciduria (PA) and methylmalonic aciduria (MMA) are rare inherited disorders caused by defects in the propionate metabolic pathway. PA due to propionyl coenzyme A carboxylase deficiency results in accumulation of propionic acid, while in MMA, deficiency in methylmalonyl coenzyme A mutase leads to accumulation of methylmalonic acid. Hyperammonemia is related to a secondary deficiency of N-acetylglutamate (NAG), the activator of carbamoyl phosphate synthetase 1, which is an irreversible rate-limiting enzyme in the urea cycle. Carglumic acid (CGA) is a synthetic structural analog of human NAG and is approved for the treatment of patients with hyperammonemia due to PA or MMA. CGA is well tolerated and its use in normalizing ammonia levels during acute hyperammonemic episodes in patients with PA and MMA is well established. This expert opinion analyzed clinical evidence for CGA and discussed its place, along with other management strategies, in the long-term management of PA or MMA. A literature search of PubMed was undertaken to identify publications related to the chronic use of CGA, transplantation, dietary management, ammonia scavengers, and gene therapy for treatment of patients with PA or MMA. The authors selected the most relevant studies for inclusion. Four clinical studies, one single center case series, and three case reports show that CGA is safe and effective in the chronic treatment of PA and MMA. In particular, the addition of CGA is associated with a reduction in hyperammonemic decompensation episodes and admission to hospital, compared with conventional dietary treatment alone. Current treatment guidelines and recommendations include the use of CGA mainly in acute decompensation, however, lag in considering the benefits of long-term CGA treatment on clinical and biochemical outcomes in patients with PA or MMA. CGA is safe and effective in the chronic treatment of PA and MMA and may help to resolve some of the issues associated with other strategies used to treat these disorders. Thus, CGA appears to have potential for the chronic management of patients with PA and MMA and should be recommended for inclusion in the chronic treatment of these disorders.
Guanidinoacetic acid supplementation and stocking density effects on broiler performance: behavior, biochemistry, immunity, and small intestinal histomorphology
Authors: Alaa Mohammad , Abdel Razek Abeer Hamada , Tony Mohamed Ahmed , Yassin Aya Mohye , Warda Mohamad , Awad Mohamed Ahmed , Bawish Basma Mohamed 
Published: December 2024

Abstract
Background
Rearing poultry under stressful high stocking density (HSD) conditions is a common commercial practice to increase profitability, despite its negative effects on broiler physiology and welfare. Many feed additives are used to alleviate the negative impact of such practices. This study investigated the ameliorative effects of guanidinoacetic acid (GAA) on growth performance, ingestive behavior, immune response, antioxidant status, stress indicators, and intestinal histomorphometry of broilers subjected to HSD. A total of 364 male broilers were randomly allocated into four treatments with 7 replicates each in a 2 × 2 factorial arrangement: two stocking densities (SD) (10 and 16 birds/m2) and two GAA levels (0 and 0.6 g/kg feed).

Results
Body weight, weight gain, feed intake, feed conversion ratio, production efficiency factor, dressing yield, and ingestive behavior were negatively affected by HSD, whereas the mortality rate was unaffected (P > 0.05). GAA improved the overall growth performance and dressing percentage (P < 0.05). In the HSD group, the immune response decreased at d 21 (P < 0.05). Creatine kinase, glutathione peroxidase (GPX), superoxide dismutase, catalase, triglycerides, and villus length and width (ileum) were reduced, whereas corticosterone (CORT) was increased (P < 0.05). Moreover, GAA increased the hemagglutination-inhibition titer at 21 days and the levels of lactate dehydrogenase, GPX, and catalase and decreased the levels of creatinine, alanine aminotransferase, nitrite, triglycerides, and CORT (P < 0.05). SD and GAA did not affect malondialdehyde or other biochemical parameters (P > 0.05).

Conclusions
Dietary GAA supplementation can improve productivity and antioxidant status and reduce stress in broilers reared in a HSD environment.
Temporal trends and social inequities in adolescent and young adult mental health disorders in Catalonia, Spain: a 2008–2022 primary care cohort study
Authors: Lozano-Sánchez Ana , Aragonès Enric , López-Jiménez Tomàs , Bennett Matthew , Evangelidou Stella , Francisco Esther , García Myriam , Malgosa Estel , Codern-Bové Núria , Guzmán-Molina Claudia , Jacques-Aviñó Constanza 
Published: December 2024

Abstract
Background
The prevalence of mental health disorders in children, teens, and young adults is rising at an alarming rate. This study aims to explore time trends in the incidence of mental disorders among young people in Catalonia, Spain from 2008 to 2022, focusing on the effects of the COVID-19 pandemic and from the perspective of social inequities.

Methods
A cohort study using primary care records from the SIDIAP database was conducted. It included 2,088,641 individuals aged 10 to 24 years. We examined the incidence of depressive, anxiety, eating, and attention deficit/hyperactivity disorders, stratified by sex, age, deprivation, and nationality.

Results
All disorders reflected an increasing trend throughout the study period: depressive disorders (IRR: 2.44, 95% CI: 2.31–2.59), anxiety disorders (IRR: 2.33, 95% CI: 2.27–2.39), ADHD (IRR: 2.33, 95%CI: 2.17–2.50), and eating disorders (IRR: 3.29, 95% CI: 3.01–3.59). A significant increase in incidence was observed after the outbreak of the COVID-19 pandemic. In 2022, anxiety disorders were most frequent, with an incidence rate (IR) of 2,537 per 100,000 persons-year (95% CI: 2,503–2,571). Depressive disorders followed with an IR of 471 (95% CI: 458–486), ADHD with an IR of 306 (95% CI: 295–317) and eating disorders with an IR of 249 (95% CI: 239–259). Significant associations were reported with sex, age, deprivation, and nationality.

Conclusion
The incidence of all studied disorders has steadily increased, reaching unprecedented levels during the pandemic. Understanding these trends is essential for an appropriate healthcare response, while addressing the non-medical determinants, requires action across all sectors of society.
Navigating recovery in childhood OCD: a qualitative analysis of barriers and facilitators
Authors: Sravanti Lakshmi , Madegowda Rajendra Kiragasur , Velusamy Arul Jayendra Pradeep , Kommu John Vijay Sagar , Girimaji Satish Chandra , Seshadri Shekhar 
Published: December 2024

Abstract
Objective
The objective is to examine barriers and facilitators to recovery in children and adolescents with obsessive-compulsive disorder (OCD) using a qualitative approach.

Methods
Ten semi-structured interviews were conducted, audio-recorded, and analyzed using thematic analysis. Findings were validated through investigator triangulation, peer validation and member check.

Results
Barriers to recovery were internal—lack of awareness; poor motivation to seek treatment; and perceived stigma, or external—poor parental support; parental anxiety; inadequate awareness in schools; social misconceptions about illness; myths about medication; and frustrations in treatment processes. Facilitators were internal—will and determination; self-discipline; keeping calm; sense of purpose, and external—general awareness; parental support; peer support; and good therapeutic engagement.

Conclusions
To the best of our knowledge, this is the first study to explore barriers and facilitators to recovery in-depth in pediatric OCD. Findings underscore the importance of tailored interventions, robust support networks, and cultural sensitivity for successful recovery outcomes.
Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes
Authors: Stanaway Ian B. , Morrell Eric D. , Mabrey F. Linzee , Sathe Neha A. , Bailey Zoie , Speckmaier Sarah , Lo Jordan , Zelnick Leila R. , Himmelfarb Jonathan , Mikacenic Carmen , Evans Laura , Wurfel Mark M. , Bhatraju Pavan K. 
Published: December 2024

Abstract

Background
Patients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes.

Methods
We prospectively enrolled 173 ICU patients with sepsis from a suspected respiratory infection (87 without AKI and 86 with AKI on enrollment). Among the AKI patients, 66 were classified as AKI-SP1 and 20 as AKI-SP2 using a three-plasma biomarker classifier. Aptamer-based proteomics assessed 5,212 proteins in urine collected on ICU admission. We compared urinary protein abundances between AKI sub-phenotypes, conducted pathway analyses, tested associations with risk of RRT and blood bacteremia, and predicted AKI-SP2 class membership using LASSO.

Measurement and main results
In total, 117 urine proteins were higher in AKI-SP2, 195 were higher in AKI-SP1 (FDR < 0.05). Urinary proteins involved in inflammation and chemoattractant of neutrophils and monocytes (CXCL1 and REG3A) and oxidative stress (SOD2) were abundant in AKI-SP2, while proteins involved in collagen deposition (GP6), podocyte derived (SPOCK2), proliferation of mesenchymal cells (IL11RA), anti-inflammatory (IL10RB and TREM2) were abundant in AKI-SP1. Pathways related to immune response, complement activation and chemokine signaling were upregulated in AKI-SP2 and pathways of cell adhesion were upregulated in AKI-SP1. Overlap was present between urinary proteins that differentiated AKI sub-phenotypes and proteins that differentiated risk of RRT during hospitalization. Variable correlation was found between top aptamers and ELISA based protein assays. A LASSO derived urinary proteomic model to classify AKI-SP2 had a mean AUC of 0.86 (95% CI: 0.69–0.99).

Conclusion
Our findings suggest AKI-SP1 is characterized by a reparative, regenerative phenotype and AKI-SP2 is characterized as an immune and inflammatory phenotype associated with blood bacteremia. We identified shared biology between AKI sub-phenotypes and eventual risk of RRT highlighting potential therapeutic targets. Urine proteomics may be used to non-invasively classify SP2 participants.
A hybrid epithelial-mesenchymal transition program enables basal epithelial cells to bypass stress-induced stasis and contributes to a metaplastic breast cancer progenitor state
Authors: Caruso Joseph A. , Chen-Tanyolac Chira , Tlsty Thea D. 
Published: December 2024

Abstract
Background
Human mammary epithelial cell (HMEC) cultures encounter a stress-associated barrier termed stasis, during which most cells adopt a senescence-like phenotype. From these cultures, rare variants emerge from the basal epithelial population, re-initiating growth. Variants exhibit pre-malignant properties, including an aberrant epigenetic program that enables continued proliferation and acquisition of genetic changes. Following oncogenic transformation, variants produce tumors that recapitulate the histopathological characteristics of metaplastic breast cancer (MBC), a rare and aggressive subtype marked by the differentiation of neoplastic epithelium into squamous and mesenchymal elements.

Methods
Using a serum-free HMEC culture system, we probed the capacity for phenotypic plasticity inherent to basal epithelial cell populations from human breast tissue as they navigated stasis and emerged as variant populations.

Results
We observed robust activation of a TGF-β-dependent epithelial-mesenchymal transition (EMT) program in basal epithelial cells during stasis, followed by subsequent attenuation of this program in emerging variants. Inhibition of the TGF-β pathway or depleting the EMT regulators Snail or Slug allowed basal epithelial cells to collectively bypass stasis, demonstrating that cellular dysfunction and arrest resulting from TGF-β and EMT activation are central to this in vitro barrier. The spontaneous emergence of variants from stasis cultures was associated with a restricted EMT trajectory, characterized by the stabilization of hybrid EMT states associated with greater proliferative capacity, rather than progressing to a complete mesenchymal state characterized by irreversible growth arrest. Epigenetic mechanisms, which contributed to the dysregulated growth control characteristic of the variant phenotype, also contributed to the stability of the hybrid EMT program in variants. By overcoming the cellular dysfunction and growth arrest resulting from TGF-β and complete EMT, variants exhibited a higher oncogenic transformation efficiency compared to pre-stasis basal epithelial cells. Inhibiting the TGF-β pathway prior to stasis significantly reduced EMT in the basal epithelial population, alleviated selective pressure driving variant emergence, and also enhanced oncogenic transformation efficiency, resulting in tumors with markedly diminished metaplastic differentiation.

Conclusions
This study reveals how an epigenetic program governs basal epithelial cell fate decisions and contributes to the development of MBC progenitors by restricting access to terminal mesenchymal states that induce growth arrest and, instead, favoring hybrid EMT states with enhanced tumorigenic potential.
Stromal tumor-infiltrating lymphocytes and pathologic response to neoadjuvant chemotherapy with the addition of platinum and pembrolizumab in TNBC: a single-center real-world study
Authors: Bae Soong June , Kim Jee Hung , Kim Min Ji , Kook Yoonwon , Baek Seung Ho , Kim Jung Hyun , Moon Sohyun , Lee Seung Eun , Jeong Joon , Cha Yoon Jin , Ahn Sung Gwe 
Published: December 2024

Abstract
Background
Immunochemotherapy with pembrolizumab has been integrated into clinical practice as part of the standard-of-care for non-metastatic triple-negative breast cancer (TNBC) with high risk. We conducted a real-world study in TNBC patients treated with neoadjuvant chemotherapy to compare pathologic complete response (pCR) rates relative to stromal tumor-infiltrating lymphocytes (sTIL) across different regimens: non-carboplatin, carboplatin-, and pembrolizumab-chemotherapy.

Patients and methods
We analyzed a cohort of 450 patients with TNBC who underwent surgery following neoadjuvant chemotherapy between March 2007 and February 2024. Treatment groups included 247 non-carboplatin, 120 carboplatin, and 83 pembrolizumab-chemotherapy recipients. sTIL was evaluated in biopsied samples. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors with high sTIL (≥ 50%).

Results
The pCR rates were 32% in the non-carboplatin-, 57% in the carboplatin-, and 64% in the pembrolizumab-chemotherapy group. Ninety-two patients (20.4%) had LPBC. In LPBC, the pCR rates did not increase with the addition of carboplatin (50.0% in the non-carboplatin and 41.7% in carboplatin) but reached 83.3% with the addition of pembrolizumab and carboplatin. Among the non-LPBC, the pCR rate increased from 26.7 to 61.1% with the addition of carboplatin, but there was no difference in the pCR rate between the carboplatin and pembrolizumab groups (61.1% and 61.2%, respectively).

Conclusions
In LPBC patients, the addition of carboplatin did not result in an elevated pCR rate; however, the addition of pembrolizumab tended to raise the pCR rate. In non-LPBC, the addition of carboplatin significantly increased the pCR rate, while the addition of pembrolizumab did not have the same effect.
Lay health coaching intervention for older adults with chronic diseases: study protocol for a pragmatic randomised controlled trial
Authors: Chung Edwin K. H. , Wong Eliza Lai-Yi , Leung Hera Hiu-Wah , Yeung Dannii Y. , Yeoh Eng-Kiong , Chen Frank Youhua 
Published: December 2024

Abstract
Background
A large proportion of older adults suffer from chronic diseases. Health coaching is a promising intervention that enhances individuals’ health knowledge and supports changes in health behaviours. Even though health professionals usually conduct health coaching interventions, lay health workers from different backgrounds account for a growing segment of health coaches over the years. The planned study’s main objective is to investigate whether health coaching by lay health workers is as effective as that by health professionals.

Methods
The effects of health coaching intervention by lay health workers will be examined in comparison with that by health professionals within a single-blind, multi-centre, randomised controlled trial with a follow-up assessment after 3 months. A total of 380 community-dwelling older adults with chronic diseases will be recruited and randomly assigned using a 1:1 ratio into the intervention and control groups. The intervention group will receive a 3-month health coaching intervention delivered by lay health workers, whereas the control group will receive the intervention delivered by health professionals. Primary outcomes include patient activation, physical activity and nutrition behaviours.

Discussion
The expected findings of this study will advance the health coaching literature, research and practice by determining whether health coaching by lay health workers is as effective as that by health professionals in enhancing older adults’ knowledge, skills and confidence in chronic disease self-management and promoting changes in health behaviours. If proven effective, the inclusion of lay health workers in delivering effective self-management interventions should be advocated to reduce the over-reliance on health professionals in the primary healthcare system.

Trial registration
ISRCTN, ISRCTN73836238. Registered 8 November 2023.
Chitosan/platinum nanocubes/Mn(TPDCA)2-modified glassy carbon electrodes for the electrochemical quantification of amlodipine in unprocessed plasma samples
Authors: Khadivi-Derakhshan Saeedeh , Abbasi Mohammad , Akbarzadeh Amirhossein , Pirouzmand Mahtab , Soleymani Jafar 
Published: December 2024

AbstractA novel electrochemical probe is developed to detect amlodipine (AMD) in unprocessed plasma samples. The fabrication process involves the synthesis of platinum nanocubes (Pt NCs) and Mn(TPDCA)2 complexes, which are then immobilized them onto the glassy carbon electrode (GCE) surface. The developed electrochemical probe demonstrates exceptional detection performance, with a wide dynamic range, outstanding selectivity, and commendable reproducibility. The linear range and lower limit of detection of the developed method are 53 nM-3.5 µM and 53 nM, respectively. Electrochemical experiments have been conducted to study the kinetics of electrooxidation on the modified electrode, revealing that the process is diffusion-controlled. Furthermore, method validation studies are performed to assess the accuracy, precision, and selectivity of the sensor, demonstrating excellent performance in all these aspects. Consequently, it can be concluded that the sensor is highly suitable for practical applications in drug analysis.
Antimicrobial peptide production with Corynebacterium glutamicum on lignocellulosic side streams
Authors: Waldschitz Daniel , Neudert Mark-Richard , Kitzmüller Jakob , Bong Jae Hwi , Bus Yannick , Karner Eva Maria , Sinner Peter , Spadiut Oliver 
Published: December 2024

Abstract

Background

Biorefineries usually focus on the production of low-value commodities, such as bioethanol, platform chemicals or single cell protein. Shifting production to bioactive compounds, such as antimicrobial peptides, could provide an opportunity to increase the economic viability of biorefineries.

Results

Recombinant production of the antimicrobial peptide pediocin PA-1 in Corynebacterium glutamicum was transferred from yeast extract-based media to minimal media based on lignocellulosic spent sulfite liquor. Induced batch, fed batch, and extended batch process modes were compared for highest pediocin PA-1 production.

Conclusion

For pediocin PA-1 production on lignocellulosic residues, extended batch cultivation was identified as the optimal process mode, producing up to $$\simeq$$
≃
104 mg/L active pediocin PA-1. Moreover, the production of pediocin PA-1 on this sustainable second generation resource exceeded its state-of-the-art production on yeast extract-based media $$\simeq$$
≃
1.5-fold.
Right ventricular outflow tract doppler flow abnormalities suggestive of pulmonary embolism – case series and review
Authors: Ivičić Toni , Hamzić Jasmin , Radulović Bojana , Gornik Ivan 
Published: December 2024

Abstract
Background
Pulmonary embolism (PE) is one of the most challenging diagnoses in emergency medicine, mainly because symptoms range from asymptomatic disease to sudden death. The role of echocardiography in the workup of suspected PE has been supportive and used primarily to assess the right ventricular (RV) size and function, which is important for risk stratification. Several echocardiographic parameters described in the literature lack the desired accuracy. Recently, a potential value of less well-recognized RV outflow tract (RVOT) Doppler variables has been reported. The early systolic notching (ESN) pattern was observed in 92% of patients with high and intermediate risk PE, making it a promising sign in selected PE patients.

Case presentation
In this case series, we demonstrate a typical ESN pattern on RVOT Doppler evaluation in three patients with intermediate-risk PE presenting to our emergency department (ED). None of the patients had been previously diagnosed with pulmonary hypertension or other chronic pulmonary and cardiac disease. The pre-test probability was low. Massive proximal emboli were found on CT angiograms, involving pulmonary truncus or main pulmonary arteries. Previously, the ESN pattern was identified on a focused echocardiogram, which was the only echocardiographic indicator of increased pulmonary vascular resistance.

Conclusions
RVOT Doppler flow pattern of ESN has potential clinical utility for the detection of PE in ED patients. ESN could identify patients at higher risk, which are otherwise stratified as low risk according to the latest guidelines. Moreover, this case series illustrates that even in the absence of other echocardiographic findings of RV strain, the presence of ESN should alert to the possibility of acute PE. Further prospective studies are needed to assess its diagnostic value in a selected subgroup of patients, similar to the cases presented, that would have no other obvious reason for the altered RVOT Doppler curve.