bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Use Nutraceutical Strategies for the Irritable Bowel Syndrome?
Authors: di Michele Flavia 
Published: September 2021

Abstract:
Irritable bowel syndrome (IBS) is a chronic functional bowel disorder, often
stress-related, identified by many abdominal symptoms, the most important of which is
chronic visceral abdominal pain. Therefore, IBS commonly impairs the quality of life of
patients, moreover, it is frequently linked to depressive and anxiety symptoms. The treatment
of IBS primarily focuses on symptoms relief. Unfortunately, up to now, no efficacious
therapies have been found. Therefore, it would be important to develop new anti-
IBS interventions.
The aim of this brief review is to summarize the current evidence of nutraceutical supplementation
in IBS treatment, with probiotics, prebiotics, synbiotics, butyrate, palmitoylethanolamide
and colostrum. Since nutraceutics are over-the-counter products, the
review has the purpose to better inform the medicinal chemist and the practitioner about
the possible beneficial mechanisms and the many advantages that these therapies offer.
All of these compounds present multiple mechanisms of action, such as restoring the
physiological microbiota, potentiating gastrointestinal barrier’s function, immunomodulatory,
anti-inflammatory and antinociceptive activities.
From the literature data, it results that these compounds are not only capable of improving
IBS symptomatology, but mainly display an optimal safety and tolerability profile.
Although extensive studies must be carried out to reinforce the evidence from the so far
limited clinical trials, the supplementation with these compounds may be useful considering
the warnings of prescription medicines for special populations of patients, such as elders,
youngsters, or patients who need combination therapy. Finally, the nutraceutical approach
may improve adherence to treatment, given its better acceptance by the patients
compared to pharmacological therapy.
Rational Design and Development of HDAC Inhibitors for Breast Cancer Treatment
Authors: Mody Deepansh , Bouckaert Julie , Savvides Savvas N. , Gupta Vibha 
Published: September 2021

Background:
Breast cancer is the most prevalent cancer amongst females across the globe, and with
over 2 million new cases reported in 2018, it poses a huge economic burden to the already dwindling public
health. A dearth of therapies in the pipeline to treat triple-negative breast cancers and acquisition of resistance
against the existing line of treatments urge the need to strategize novel therapeutics in order to add new drugs to
the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone
deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks
breast cancer progression.

Objective:
While four HDACi have been approved by the FDA for the treatment of different cancer types, no
HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC
expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered.

Conclusion:
This review attempts to set the stage for the rational structure-based discovery of isoform-selective
HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes
and individual landscape. The development of inhibitors in accordance with the differential expression of
HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective
inhibitors, adopting a ‘personalized-medicine’ approach.
Key Performance Indicators in Claims Management: Definition of a Set of Indicators for the Evaluation of the Medico-Legal Activity
Authors: Scopetti Matteo , Padovano Martina , Manetti Federico , Gatto Vittorio , D’Errico Stefano , Santurro Alessandro , Frati Paola , Fineschi Vittorio 
Published: September 2021

Background:
In recent decades, in the field of healthcare, awareness of the problems inherent
to the quality has steadily increased. Currently, the evaluation of healthcare activities is one of the
ways in which health systems regulate internal relationships and define strategic decisions.

Objective:
The study aims to describe in detail the entire process of developing a group of Key Performance
Indicators for monitoring and implementing the management of litigation due to medical liability.
Particularly, the objective is to centralize and standardize the indicators to provide scientifically
reliable data on claims management to hospital professionals responsible for strategic choices.

Methods:
The study was conducted to analyze data relating to the claims management at Umberto I
General Hospital in Rome from 2012 to 2018. All claims reported were classified according to a selection
of the categories coded in the International Classification for Patient Safety system, the economic
features, and the chronological references of the main management extrajudicial and judicial phases.
The Process Analysis Method was followed to develop significant indicators for measuring the performance
and the quality of claims management.

Results and Conclusion:
The results obtained demonstrate how the assessment of performance in
claims management can potentially lead to greater risk control with significant repercussions in terms
of reduction of disputes, speed in settling claims, reduction of management times, planning of loss prevention
measures, and implementation of quality of care.
Diabetes and Lung Cancer: A Sweet and Sour Relationship
Authors: Hardavella Georgia , Paraskevas Andreas , Bellou Elena , Keramida Elli , Bracka Irma , Gkriniouk Christina , Mazarakis Spyros , Karampinis Ioannis , Demertzis Panagiotis 
Published: September 2021

Introduction:
Diabetes mellitus and lung cancer are two highly prevalent diseases on a
global scale. The association between these two diseases has been the subject of study of many cohorts
in the past, some of which presenting inconclusive results.

Aim:
To present existing evidence regarding the association of diabetes with lung cancer risk and
survival as well as the impact of metformin and insulin on lung cancer.

Methods:
A narrative review of all the relevant published literature known to the authors was conducted.
The references were identified by searching the Pubmed online database using the keywords
such as diabetes and lung cancer risk, diabetes and lung cancer survival rates, metformin
and lung cancer, insulin and lung cancer.

Results :
Although previous epidemiologic studies have failed to report any significant causal effect
of diabetes on lung cancer risk, recent evidence from 2 large scale meta-analyses of observational
studies and other studies showed a statistically significant correlation between nonsmoker diabetics
and lung cancer risk (RR, 1.11; 95% CI, 1.02-1.20; I2 = 46.1% and RR, 1.14; 95% CI, 1.09-1.20;
I2 = 0%). Recent evidence has shown that metformin is related to a lower risk of lung cancer incidence
among never-smokers diabetic patients (HR, 0.57;95% CI, 0.33-0.99) and improved overall
survival rates (HR=0.77, 95%CI=0.66-0.9, P=0.001) regardless of the histological type of lung cancer.
On the other hand, a recently published large population-based retrospective cohort study has
concluded that human insulin is associated with an increased risk of lung cancer (HR 1.545, 95%
CI: 1.478-1.614). Interestingly, metformin has been reported to have an anti-resistant effect on
lung cancer patients who are on Epidermal Growth Factor Receptor- Tyrosine Kinase Inhibitors, offering
some protection against resistance to therapy.

Conclusion:
Published evidence shows that diabetes mellitus is associated with an increased risk
of lung cancer and worse survival rates. Metformin plays a protective role in lung cancer pathogenesis
and is also associated with prolonged progression-free survival in lung cancer patients with diabetes.
There is a significant association between human insulin use and lung cancer risk. More randomized
controlled studies are required to establish the positive association of diabetes and anti-diabetic
drugs with lung cancer, taking into further consideration gender and lung cancer pathology as
well as possible confounders such as smoking habits that can influence the results of these studies.
Pleomorphic Invasive Lobular Cancer of the Breast Presenting with Orbital
Metastasis: A Case Report
Authors: Arslan Aydan , Yılmaz Ebru , Güldoğan Nilgün , Civan Ceyda 
Published: September 2021

Background:
Orbital metastasis of breast cancer is an unusual condition, especially in
the absence of a previous diagnosis of primary breast cancer. The main MRI findings in patients
with orbital metastasis are retroorbital soft tissue with thickening of extraocular muscles. Paradoxical
enophthalmos secondary to fibrosis can be seen.

Case Report:
In this case report, we present a 75-year-old female patient with left eye pain and
blurred vision and retraction. Although there was no evidence of malignancy in the biopsy of the orbita;
since the patient's complaints continued despite idiopathic pseudotumor treatment, mammography
was recommended to rule out the possibility of breast cancer metastasis. Her mammography revealed
a suspicious lesion in the left breast and proved to be pleomorphic invasive lobular cancer.

Conclusion:
Breast cancer metastasis should be kept in mind in women with pseudotumor -like the
involvement of the orbita.
Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus
Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic
Spectral DCM Study
Authors: Stoyanov Drozdstoy , Kandilarova Sevdalina , Aryutova Katrin , Paunova Rossitsa , Mantarkov Mladen , Mitrev Ivo , Todeva-Radneva Anna , Specht Karsten 
Published: September 2021

Background & Objective:
We have previously identified aberrant connectivity of the
left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients
with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar).
In the current study, we attempted to replicate and expand these findings by including a healthy
control sample and separating the patients in a depressive episode into two groups: unipolar and
bipolar depression. We hypothesized that the connections between those major nodes of the resting
state networks would demonstrate different patterns in the three patient groups compared to the
healthy subjects.

Method:
Resting-state functional MRI was performed on a sample of 101 participants, of which
26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD),
33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive
episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate
the coupling values between eight regions of interest, including the anterior precuneus (PRC),
anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle
frontal gyrus, planum temporale, and anterior thalamus.

Results & Conclusion:
We identified disturbed effective connectivity from the left lateral orbitofrontal
cortex to the left anterior precuneus that differed significantly between unipolar depression,
where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A
logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression
based solely on the coupling values of this connection. In addition, patients with schizophrenia
demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which
distinguished them from healthy controls and patients with major depression. Future studies with
unmedicated patients will be needed to establish the replicability of our findings.
Probiotic Properties of a Spaceflight-induced Mutant Lactobacillus Plant-
arum SS18-50 in Mice
Authors: Wang Dan , Zhang Tiehua , Hao Hongwei , Zhang Hongxing , Ye Haiqing , Zhao Changhui 
Published: September 2021

Background:
Probiotics are a group of bacteria that play a critical role in intestinal microbiota
homeostasis and may help adjunctively treat certain diseases like metabolic and immune
disorders.

Objective:
We recently generated a space-flight mutated Lactobacillus plantarum SS18-50 with
good in vitro probiotic characteristics. In the current research, we designed two in vivo experiments
to evaluate whether L. plantarum SS18-50 had the ability to increase beneficial gut bacteria, regulate
oxidative status and ameliorate inflammation in mice.

Methods:
Experiments I: the ICR mice were gavaged with L. plantarum SS18-50 or its wild type
L. plantarum GS18 at 107 or 109 CFU/kg BW daily for one month, during which the body weight
was recorded weekly. The feces were collected to determine the abundance of two main beneficial
bacterial groups including Lactobacillus and Bifidobacterium by selective culturing, while the total
triglycerides and cholesterols in sera were determined using commercial kits. Experiment II: the
mice were gavaged with loperamide hydrochloride (Lop) to develop oxidative stress and inflammation
phenotypes. At the same time, the experimental mice were gavaged with L. plantarum
SS18-50 or wild type L. plantarum GS18 at 107 or 109 CFU/kg BW daily for one month. At the end
of the experiment, oxidative indicators (SOD and MDA) and inflammatory cytokines (IL-17A and
IL-10) were measured by commercial kits.

Results:
Results showed that L. plantarum SS18-50 increased the abundance of Lactobacillus and
Bifidobacterium in mice after one month’s administration. L. plantarum SS18-50 also showed the
anti-oxidant activity by increasing SOD and decreasing MDA and exerted the anti-inflammatory effect
by increasing IL-10 and decreasing IL-17A in Lop treated mice. Both the wild type stain and
the space mutant had such biomedical effects, but L. plantarum SS18-50 was better in increasing
gut beneficial bacteria and oxidative regulation than the wild type (P<0.05).

Conclusion:
We conclude that L. plantarum SS18-50 has a great potential to serve as a dietary
functional probiotic supplement and/or adjunctive treatment strategy.
Key miRNAs in Modulating Aging and Longevity: A Focus on Signaling
Pathways and Cellular Targets
Authors: Zia Aliabbas , Farkhondeh Tahereh , Sahebdel Faezeh , Pourbagher-Shahri Ali Mohammad , Samarghandian Saeed 
Published: September 2021

:
Aging is a multifactorial process accompanied by gradual deterioration of most biological
procedures of cells. MicroRNAs (miRNAs) are a class of short non-coding RNAs that post-transcriptionally
regulate the expression of mRNAs through sequence-specific binding, contributing to
many crucial aspects of cell biology. Several miRNAs are expressed differently in various organisms
through aging. The function of miRNAs in modulating aging procedures has been disclosed
recently with the detection of miRNAs that modulate longevity in the invertebrate model organisms
through the IIS pathway. In these model organisms, several miRNAs have been detected
to both negatively and positively regulate lifespan via commonly aging pathways. miRNAs modulate
age-related procedures and disorders in different mammalian tissues by measuring their tissue-
specific expression in older and younger counterparts, including heart, skin, bone, brain, and
muscle tissues. Moreover, several miRNAs have contributed to modulating senescence in different
human cells, and the roles of these miRNAs in modulating cellular senescence have allowed illustrating
some mechanisms of aging. The review discusses the available data on the role of miRNAs
in the aging process, and the roles of miRNAs as aging biomarkers and regulators of longevity in
cellular senescence, tissue aging, and organism lifespan have been highlighted.
Exploring the Intersection Between Health Professionals’ Learning and eHealth Data: Protocol for a Comprehensive Research Program in Practice Analytics in Health Care
Authors: Janssen Anna , Talic Stella , Gasevic Dragan , Kay Judy , Shaw Tim 
Published: September 2021

Background
There is an increasing amount of electronic data sitting within the health system. These data have untapped potential to improve clinical practice if extracted efficiently and harnessed to change the behavior of health professionals. Furthermore, there is an increasing expectation from the government and peak bodies that both individual health professionals and health care organizations will use electronic data for a range of applications, including improving health service delivery and informing clinical practice and professional accreditation.

Objective
The aim of this research program is to make eHealth data captured within tertiary health care organizations more actionable to health professionals for use in practice reflection, professional development, and other quality improvement activities.

Methods
A multidisciplinary approach was used to connect academic experts from core disciplines of health and medicine, education and learning sciences, and engineering and information communication technology with government and health service partners to identify key problems preventing the health care industry from using electronic data to support health professional learning. This multidisciplinary approach was used to design a large-scale research program to solve the problem of making eHealth data more accessible to health professionals for practice reflection. The program will be delivered over 5 years by doctoral candidates undertaking research projects with discrete aims that run in parallel to achieving this program’s objectives.

Results
The process used to develop the research program identified 7 doctoral research projects to answer the program objectives, split across 3 streams.

Conclusions
This research program has the potential to successfully unpack electronic data siloed within clinical sites and enable health professionals to use them to reflect on their practice and deliver informed and improved care. The program will contribute to current practices by fostering stronger connections between industry and academia, interlinking doctoral research projects to solve complex problems, and creating new knowledge for clinical sites on how data can be used to understand and improve performance. Furthermore, the program aims to affect policy by developing insights on how professional development programs may be strengthened to enhance their alignment with clinical practice. The key contributions of this paper include the introduction of a new conceptualized research program, Practice Analytics in Health care, by describing the foundational academic disciplines that the program is formed of and presenting scientific methods for its design and development.

International Registered Report Identifier (IRRID)
PRR1-10.2196/27984
Impact of a Mobile Telerehabilitation Solution on Metabolic Health Outcomes and Rehabilitation Adherence in Patients With Obesity: Randomized Controlled Trial
Authors: Bughin François , Bui Gaspard , Ayoub Bronia , Blervaque Leo , Saey Didier , Avignon Antoine , Brun Jean Frédéric , Molinari Nicolas , Pomies Pascal , Mercier Jacques , Gouzi Fares , Hayot Maurice 
Published: September 2021

Background
Obesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components.

Objective
The aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity.

Methods
This was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients’ adhesion, and satisfaction.

Results
A total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: −0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: −1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good.

Conclusions
In adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients’ adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care.

Trial Registration
ClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT03396666