bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis
Authors: Vélez-Pinto J. F. , Garcia-Arranz M. , García-Bernal D. , García Gómez-Heras S. , Villarejo-Campos P. , García-Hernández A. M. , Vega-Clemente L. , Jiménez-Galanes S. , Guadalajara H. , Moraleda J. M. , García-Olmo D. 
Published: December 2023

Abstract
Background
The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.

Methods
We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.

Results
One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.

Conclusions
Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.
SARS-CoV-2-infected hiPSC-derived cardiomyocytes reveal dynamic changes in the COVID-19 hearts
Authors: Li Xiao , Hu Hengrui , Liu Wanlin , Zhang Qiyu , Wang Yujie , Chen Xingjuan , Zhu Yunping , Hu Zhihong , Wang Manli , Ma Jie , Leng Ling 
Published: December 2023

Abstract
Background
The ongoing coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on our societies. Moreover, the disease’s extensive and sustained symptoms are now becoming a nonnegligible medical challenge. In this respect, data indicate that heart failure is one of the most common readmission diagnoses among COVID-19 patients.

Methods
In this study, we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to develop an in vitro model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and studied the dynamic changes occurring in cardiomyocytes after SARS-CoV-2 infection.

Results
To this end, we have created an effective time series SARS-CoV-2 infection model exhibiting different functional patterns of up- and downregulated proteins, and demonstrating that SARS-CoV-2 mainly affects (i) the lipid and the energy metabolism of hiPSC-derived cardiomyocytes during the early infection stage, and (ii) the DNA repair ability of cardiomyocytes during the late infection stage. By analyzing the proteome changes occurring at different infection timepoints, we were able to observe that the simulated disease (COVID-19) course developed rapidly, and that each of the studied timepoints was characterized by a distinct protein expression pattern.

Conclusions
Our findings highlight the importance of early detection and personalized treatment based on the disease stage. Finally, by combing the proteomics data with virus-host interaction network analysis, we were able to identify several potential drug targets for the disease.
On measure of noncompactness in variable exponent Lebesgue spaces and applications to integral equations
Authors: Metwali Mohamed M. A. 
Published: December 2023

AbstractA novel measure of noncompactness is defined in variable exponent Lebesgue spaces $L^{p(\cdot )}$

L

p
(
⋅
)

on an unbounded domain $\mathbb{R}^{+}$

R
+

and its properties are examined. Using the fixed point method, we apply that measure to study the existence theorem for nonlinear integral equations. Our results can be handily applied in studying various types of (differential, integral, functional, and partial differential) equations in $L^{p(\cdot )}$

L

p
(
⋅
)

-spaces. The $L^{p(\cdot )} $

L

p
(
⋅
)

-spaces are natural extensions of classical constant exponent Lebesgue spaces $L_{p}$

L
p

, which allows us to bypass several restrictions that were previously discussed in the literature.
Current status and challenges of breast cancer prevention~DNA methylation would lead to groundbreaking progress in breast cancer prevention~
Authors: Tsukioki Takahiro , Khan Seema A. , Shien Tadahiko 
Published: December 2023

AbstractThe number of breast cancer patients is increasing worldwide. Furthermore, breast cancer often develops in young people, even those only in their 30s, who play a central role in their families and society. Results from many cohort studies suggest that dietary factors, alcohol consumption, lack of physical activity, obesity, nulliparity, breastfeeding, oral contraceptive use, fertility treatment and hormone replacement therapy are risk factors for breast cancer. However, the effects of lifestyle habits on the human body are complexly intertwined with various factors, and the effects vary from person to person depending on their constitution, etc., so there is no basis for this. Therefore, primary prevention of breast cancer is still not being implemented appropriately and efficiently. Furthermore, advances in genomic technology make it possible to assess the risk of developing breast cancer in some individuals. As a result, the establishment of breast cancer prevention methods has become a health priority for high-risk individuals.Drugs such as tamoxifen and raloxifene are known to prevent the development of breast cancer, based on the results of multiple randomized controlled trials, but there are concerns regarding the side effects of these powerful agents. In addition, several clinical studies have shown that prophylactic mastectomy for women who have BRCA mutations or who are identified as being at high risk reduces the incidence of breast cancer development. However, many issues, such as changes in long-term quality of life after preventive surgery, the optimal timing of surgery and the identification of women who are at high risk but will not develop breast cancer, remain uncertain. In other words, although many researchers have focused on chemoprevention and surgical prevention and clear preventive effects of these strategies have been confirmed, it cannot be said that they are widely accepted. Therefore, the current evidence for chemoprevention and surgical prevention, as well as highlights of several interesting lines of research currently underway, are summarized in this article.
Inter-organ communication involved in metabolic regulation at the whole-body level
Authors: Katagiri Hideki 
Published: December 2023

AbstractMetabolism in each organ of multi-organ organisms, including humans, is regulated in a coordinated manner to dynamically maintain whole-body homeostasis. Metabolic information exchange among organs/tissues, i.e., inter-organ communication, which is necessary for this purpose, has been a subject of ongoing research. In particular, it has become clear that metabolism of energy, glucose, lipids, and amino acids is dynamically regulated at the whole-body level mediated by the nervous system, including afferent, central, and efferent nerves. These findings imply that the central nervous system obtains metabolic information from peripheral organs at all times and sends signals selectively to peripheral organs/tissues to maintain metabolic homeostasis, and that the liver plays an important role in sensing and transmitting information on the metabolic status of the body. Furthermore, the utilization of these endogenous mechanisms is expected to lead to the development of novel preventive/curative therapies for metabolic diseases such as diabetes and obesity.(This is a summarized version of the subject matter presented at Symposium 7 presented at the 43rd Annual Meeting of the Japanese Society of Inflammation and Regeneration.)
A country report: impact of COVID-19 lockdowns on involuntary psychiatric treatment in Austria
Authors: Fellinger Matthäus , Waldhör Thomas , Vyssoki Benjamin , Amering Michaela , Leutgeb Lisa , Gschaider Andreas , Rappert Bernhard , König Daniel , Fugger Gernot , Knasmüller Philipp , Gmeiner Andrea 
Published: December 2023

Background
Coercive measures such as involuntary psychiatric admission are considered a last resort in the treatment of people with psychiatric disorders. So far, numerous factors have been identified that influence their use. However, the link between a pandemic – in particular, restrictions such as lockdowns – and the use of involuntary psychiatric admission is unclear.

Aim
To examine the association between COVID-19 lockdowns and involuntary psychiatric admissions in Austria.

Method
This retrospective exploratory study assessed all involuntary psychiatric admissions and use of mechanical restraint in Austria, except for the federal state of Vorarlberg, between 1 January 2018 and 31 December 2020. Descriptive statistics and regression models were used.

Results
During the 3-year study period, 40 012 individuals (45.9% females, mean age 51.3 years) had 66 124 involuntary psychiatric admissions for an average of 10.9 days. Mechanical restraint was used during 33.9% of these admissions. In weeks of nationwide COVID-19 lockdowns (2020 v. 2018/2019), involuntary psychiatric admissions were significantly fewer (odds ratio = 0.93, P = 0.0001) but longer (11.6 (s.d.: 16) v. 10.9 (s.d.: 15.8) days). The likelihood of involuntary admission during lockdowns was associated with year (2020 v. 2018–2019; adjusted odds ratio = 0.92; P = 0.0002) but not with sex (P = 0.814), age (P = 0.310), use of mechanical restraint (P = 0.653) or type of ward (P = 0.843).

Conclusions
Restrictions such as lockdowns affect coercive measures and resulted in fewer but longer involuntary psychiatric admissions during weeks of lockdown in Austria. These results strengthen previous findings that showed the dependence of coercive measures on external factors, highlighting the need to further clarify causality and desired prevention effects when using coercive measures.
Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing
Authors: Sharma Ankur , Liu Xin , Chandra Vishal , Rai Rajani , Benbrook Doris M. , Woo Sukyung 
Published: December 2023

AbstractSHetA2 is a promising, orally active small molecule with anticancer properties that target heat shock proteins. In this study, we aimed to investigate the pharmacodynamic (PD) effects of SHetA2 using preclinical in vitro and in vivo models of ovarian cancer and establish a physiologically based pharmacokinetic (PBPK)/PD model to describe their relationships with SHetA2 concentrations in mice. We found that daily oral administration of 60 mg/kg SHetA2 for 7 days resulted in consistent plasma PK and tissue distribution, achieving tumor drug concentrations required for growth inhibition in ovarian cancer cell lines. SHetA2 effectively induced cyclin D1 degradation in cancer cells in a dose-dependent manner, with up to 70% reduction observed and an IC50 of 4~5 µM. We identified cyclin D1 as a potential PD marker for SHetA2, based on a well-correlated time profile with SHetA2 PK. Additionally, we examined circulating levels of ccK18 as a non-invasive PD marker for SHetA2-induced apoptotic activity and found it unsuitable due to high variability. Using a PBPK/PD model, we depicted SHetA2 levels and their promoting effects on cyclin D1 degradation in tumors following multiple oral doses. The model suggested that twice-daily dosing regimens would be effective for sustained reduction in cyclin D1 protein. Our study provides valuable insights into the PK/PD of SHetA2, facilitating future clinical trial designs and dosing schedules.
Noninstrumented Free Fibula Flap for Cervical Osteomyelitis
Authors: Bindal Shivani , Fairchild Berry , Lamaris Gregory A. , Cochran Joseph A. 
Published: December 2023

BACKGROUND AND IMPORTANCE:
Severe cases of cervical vertebral osteomyelitis can pose a challenge regarding reconstruction, stability/alignment, and infection eradication. Here we describe the application of vascularized free fibula (FF) flaps to reconstruct the cervical spine without instrumentation in the setting of severe osteomyelitis.

CLINICAL PRESENTATION:
Two patients presented with symptomatic multilevel cervical osteomyelitis. Both patients were treated with corpectomy and FF flap without instrumentation using a novel wedging and distraction technique to secure the flap into position. Clinical outcomes were based on neurological recovery and infection management. Computed tomography (CT) and CT angiography with 3-dimensional reconstruction were used to measure fusion status and patency of the anastomoses. CT of the cervical spine completed 8 weeks postoperatively demonstrated robust fusion of the fibula flaps to adjacent cervical vertebrae. In both patients, CT angiography demonstrated patency of the arterial anastomoses. Both flaps maintained persistent deformity correction. Both patients made full neurological recovery.

DISCUSSION:
This reconstructive approach represents a salvage technique that offers advantages in cases of prior hardware failure or unfavorable host factors with rapid fusion and definitive treatment with a single surgery.

CONCLUSION:
The use of FF flap without instrumentation seems to be a safe and effective option for cervical spine reconstruction in the setting of severe osteomyelitis.
ANEMIA IN PATIENTS WITH MALIGNANT NEOPLASMS (literature review)
Authors: Kel'berer E. 
Published: December 2023

Anemia is a common complication of both oncopathology itself and ongoing drug and chemoradiotherapy. Anemia not only worsens the quality of life of patients, but also negatively affects the effectiveness of specific treatment and patient survival rates. The frequency of anemia varies from 20 to 90% depending on the nosology, the stage of the disease, and the antitumor treatment being carried out.
In cancer patients, anemia has a complex origin and can be caused by various reasons. As a rule, there are a number of factors at once, among which the suppressive effect of proinflammatory cytokines on erythropoiesis, synthesis of endogenous erythropoietin, sensitivity of erythropoietin receptors, as well as increased formation of hepcidin with the development of functional iron deficiency prevail.
A detailed understanding of the pathogenesis of anemia caused by a tumor or chronic disease will allow the clinician to build a competent tactic for correcting the anemia syndrome, which will timely prevent the development of clinical symptoms and aggravation of the severity of the cancer patient's condition.
DEFESA DOS DIREITOS DA NATUREZA: SIERRA CLUB v MORTON 405 U.S. 727 (1972) (MINERAL KING)
Authors: Antunes Paulo De Bessa 
Published: December 2023

RESUMO: o artigo tem por objetivo examimar a evolução da discussão judicial sobre os direitos da natureza e demonstrar que a concepção ed tais direitos e o valor a eles atribuídos é função das diferentes relações sociais e, em especial, da forma como as diferentes sociedades entendem a a propriação social da natureza. Metodologicamente, o artigo correlaciona decisõe judiciais relacionadas ao tema em diferentes países em diferentes graus de desenvolvimento. A partir de tal exposição, fica claro que não se pode considerer abstratamente os direitos da natreza, mas é essencial que se perceba os fundamentos básicos que levam à reivindicação de tais direitos em diferentes sociedades. ABSTRACT: The article aims to examine the evolution of the judicial discussion on the rights of nature and demonstrate that the conception of such rights and the value attributed to them is a function of different social relations and the way different societies understand the social appropriation of nature. Methodologically, the article correlates judicial decisions related to the subject in different countries with different degrees of development. From such an exposition, one cannot abstractly consider the rights of nature, but it is essential to understand the basic foundations that lead to the claim of such rights in different societies.
O Caso das Papeleiras (Uruguai vs Argentina) e as obrigações ambientais internacionais
Authors: Crêspo Casado Beatriz , Queiroz Farias Talden 
Published: December 2023

O Caso das Papeleiras foi trazido perante a Corte Internacional de Justiça (CIJ) em 2006 e representou marco histórico no Direito Internacional do Meio Ambiente. A disputa foi fundada em razão da autorização de construção e operacionalização pelo governo uruguaio de duas estações de usinas de papel no curso dotransfronteiriço Rio Uruguai, o que provocou a insurgência daArgentina por alegado descumprimento do Tratado sobre o Rio Uruguai de 1961. Em emblemático julgamento, a CIJ decidiu e declarou que o Uruguai violou obrigações procedimentais, inexistindo, todavia, mácula às obrigações substanciais ouevidências de que o país não teria agido com a Devida Diligência. Embora ressaltada a importância da administração mútua na prevenção de danos em recursos compartilhados, o indeferimento parcial dos pleitos frustrou a Argentina, que esperava conclusõesmais assertivas. O presente artigo, portanto, apresenta estudo de caso conduzido a partir de análise documental e bibliográfica, extraindo reflexões sobre o descumprimento de obrigações de forma consciente e continuada, assim como enaltecendo as relevantes contribuições às obrigações ambientais promovidas pela jurisprudência internacional. A partir da análise, evidencia-setimidez no tratamento aos princípios da prevenção e da precaução, refletindo-se se há como dissociar as obrigações procedimentais das obrigações substanciais.
Narcissism, pride, envy, lust and dentistry
Authors: Kelleher Martin , Newton J Tim 
Published: December 2023

Platforms such as Instagram have normalized self-adulation and this has affected many patients, and some dentists, in different ways. Some posts demonstrate excessive pride in the appearance of the mouth or face, and seem designed to induce envy in others. The resultant emotional impacts on envious followers can increase demands to have a similar sort of appearance, which can lead to over-treatment, or to potentially dangerous procedures being carried out on their mouth and face regions. This article explores the nature of narcissism and the increasing likelihood of it being ‘normalized’ as one significant factor in the increased demand for, and the delivery of, some questionable dental, oral and/or facial treatments. We outline how the narcissistic traits in some dental healthcare professionals might lead them to undertake elective, biologically risky, and irreversible procedures, which can invoke ‘the law of unintended consequences’ for patients and/or themselves. The terms ‘destructodontics’ ‘relapsodontics’ and ‘alignerodontics’ are suggested as being appropriate descriptions for some dentistry, which is carried out mainly for appearance reasons, but which can produce long-term biological and other problems. CPD/Clinical Relevance: The normalization of narcissism, as demonstrated by some posts on Instagram and other platforms and in dubious advertising has many worrying implications and possible consequences for patients and the dental profession.
Restorative management of the posterior tooth that has undergone a pulpotomy
Authors: Longridge Nicholas N , Hyde James S , Jarad Fadi , Albadri Sondos 
Published: December 2023

Pulpotomy is increasingly being recognized as a treatment option for the management of permanent teeth with extremely deep caries. These teeth can present with or without symptoms of pulpitis. Traditionally, irreversible pulpitis has been managed with pulp extirpation and root canal treatment. Contemporary research has shown that pulpotomy may be suitable to manage permanent teeth diagnosed with irreversible pulpitis. This article discusses the options and decision-making process of how to restore posterior permanent teeth that have undergone a pulpotomy. In addition, the article highlights diagnostic and material considerations relating to the role of pulpotomy in managing deep caries. CPD/Clinical Relevance: Clinicians should be aware of the use of pulpotomy in management of extremely deep caries or partial irreversible pulpitis in permanent teeth.
A case of a mandibular dentigerous cyst in a paediatric patient
Authors: Goel Aditi , Mumtaz Shadaab , Creedon Alex 
Published: December 2023

Cystic lesions of the jaw in the paediatric population have been infrequently documented in the literature. The majority of these lesions are considered to be developmental in nature, as opposed to the commonly noted inflammatory lesions in the adults. Although asymptomatic, these lesions are associated with a high level of anxiety for parents. Early diagnosis and management help to allay anxiety. We present a case of 6-year-old boy who had a rapidly growing lucent lesion of the mandible that needed urgent intervention. The lesion was excised, analysed histopathologically, and confirmed as a dentigerous cyst. The management of paediatric cystic lesions can be difficult and vary significantly from those of the adult population. This can be amplified because cross-sectional imaging is seldom used in children owing to the risk associated with radiation. We present our experience of dealing with rapidly progressing lesion and the lessons learned in the process. CPD/Clinical Relevance: The management of paediatric cystic lesions can be difficult and vary significantly from those of the adult population.
The role of the maxillary labial frenectomy in closure of the midline diastema: A review and management recommendations
Authors: DeSeta Michaela , Nurse Janelle , Ashley Paul , Noar Joseph , Parekh Susan 
Published: December 2023

A maxillary midline diastema is often seen in childhood as part of physiological development, but those persisting after the establishment of the permanent dentition may be a functional and aesthetic concern for which patients seek treatment. The association between an enlarged maxillary labial frenum and a maxillary midline diastema is commonly reported in the literature. However, the aetiologic role of an enlarged frenum is likely to represent only a proportion of diastema cases, and many diastemas exist without the presence of an abnormal frenum. This article provides an overview of the maxillary labial frenectomy and its role in closure of the midline diastema, providing management recommendations for practitioners. CPD/Clinical Relevance: The association between an enlarged maxillary labial frenum and a midline diastema and the management options is useful clinical information