bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutrition-focused group intervention with a strength-based counseling approach for people with clinical depression: a study protocol for the Food for Mind randomized controlled trial
Authors: Roponen Johanna , Ruusunen Anu , Absetz Pilvikki , Partonen Timo , Kuvaja-Köllner Virpi , Hujo Mika , Nuutinen Outi 
Published: May 2021

Abstract
Background
Depression is a highly prevalent mental disorder with major public health effects globally. It impairs the quality of life and reduces the ability to work and function, leading to increasing costs of sick leaves and disability pensions. Current treatment strategies focus on biological and psychological pathways while understating the role of lifestyle factors. Epidemiological studies have shown convincing evidence of an inverse relationship between diet quality and depression. However, only limited data are available on the therapeutic effects of diet quality improvement on depression. Using a randomized controlled trial design, our primary aim is to investigate the effectiveness and cost-effectiveness of a behavioral nutrition group intervention compared to a social support intervention in the treatment of depression.

Methods
Participants (N=144, aged 20–65 years) with a diagnosis of moderate or severe depression recruited in collaboration with outpatient care units will be randomized into two arms: Food for Mind (FM) nutrition intervention (n=72) or Bring Good Mood (BGM) social support control group (n=72). Both arms will be provided with 6 group sessions over an 8-week period. FM involves improving diet quality by applying strength-based behavioral nutrition counseling and activities facilitated by a registered dietitian. The control arm comprises a befriending protocol. During the interventions, all participants will continue their treatment for depression as usual. Longitudinal data are collected at baseline, at 8 weeks, and at 6- and 12-month follow-ups. Depressive symptoms, diet quality, eating behavior, ability to work and function, and quality of life are assessed by self-reported questionnaires. A treatment expectancy questionnaire will be administered at baseline and an acceptability questionnaire at 8 weeks. The Center for Epidemiologic Studies Depression Scale is used as the primary endpoint at 1 year. The results will be analyzed with linear mixed-effects models. Economic evaluation includes both cost-effectiveness and cost-utility analysis. Two incremental cost-effectiveness ratios will be calculated to evaluate the incremental cost per QALY and the incremental cost per improvement in CES-D.

Discussion
If the intervention proves to be cost-effective and acceptable, it be can be implemented in healthcare to support the treatment of depression.

Trial registration
ClinicalTrials.gov NCT03904771. Retrospectively registered on 5 April 2019
Parent engagement in co-design of clinical trials: the PARENT trial
Authors: Vanderloo Leigh M. , Vanderhout Shelley M. , Tavares Erika , Maguire Jonathon , Straus Sharon , Birken Catherine S. 
Published: May 2021

AbstractEvidence generated from partnering with parents to design and conduct research together may be used to refine, adjust, and modify future research approaches. This study aimed to describe the initial approaches to parent engagement in the design of the PARENT trial as well as understand parent perspectives on the acceptability and relevance of the PARENT trial and potential barriers and facilitators to participation.Parents participating in the TARGet Kids! cohort were invited to participate in a focus group, called the PARENT panel, to co-design the PARENT trial. This focus group was conducted to capture diverse individual and collective parents’ experiences. Overall methodological approaches for the PARENT panel were informed by the CIHR Strategy for Patient Oriented Research (SPOR) guiding principles (mutual respect, co-building, inclusiveness, and support) for patient engagement in research, and facilitated through the Knowledge Translation Program in the Li Ka Shing Knowledge Institute at Unity Health Toronto. Using a Nominal Group Technique, the PARENT panel provided feedback on the feasibility, relevance, and acceptability of the proposed intervention. Findings from this work will be used to further refine, adjust, and modify the next iteration of the PARENT trial, which will also serve as an opportunity to discuss the efforts made by researchers to incorporate parent suggestions and what additional steps are required for improved patient engagement.
Effectiveness of Credelio® Plus, a novel chewable tablet containing milbemycin oxime and lotilaner for the treatment of larval and immature adult stages of Toxocara canis in experimentally infected dogs
Authors: Young Lisa M. , Wiseman Scott , Crawley Elizabeth , Bowman Dwight D. , Reinemeyer Craig R. , Snyder Daniel E. 
Published: May 2021

Abstract
Background
The ascarid, Toxocara canis, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. An effective treatment that kills any pre-patent stages of immature T. canis could additionally reduce or eliminate the development of patent infections that can result in clinical disease in infected dogs and would further reduce environmental contamination of eggs. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to assess the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus) administered orally to dogs that were experimentally infected with immature (L4 or immature adult [L5]) stages of T. canis.

Methods
The commercial tablet formulation of Credelio Plus® was administered in a time frame relative to inoculation with infective eggs. This allowed for effectiveness to be assessed against each specific immature stage of T. canis. In each study, dogs were randomized and allocated to one of four treatment groups. Each treatment group contained ten dogs that had been experimentally inoculated on Day 0 with infective T. canis eggs and then were dosed once on Day 14 or Day 24 using either placebo tablets or Credelio Plus tablets (IP) to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 or 6 days after their respective treatment. At necropsy, all nematodes recovered from the gastrointestinal tract were counted by species and stage.

Results
In both dose confirmation studies using geometric mean worm counts, effectiveness of Credelio Plus was ≥ 98.6% and ≥ 96.8% against L4 larval stage T. canis and immature adult [L5] T. canis in both studies, respectively.

Conclusions
These studies demonstrated that the Credelio Plus combination tablet administered orally to dogs was highly efficacious against experimental infections with L4 and immature adult [L5] stages of T. canis.

Graphical Abstract
Effects of Zataria multiflora essential oil on the germinative cells of Echinococcus granulosus
Authors: Kowsari Nasim , Moazeni Mohammad , Mohammadi Ali 
Published: May 2021

Abstract
Background
Novel and more efficient compounds are urgently required for medical treatment of cystic echinococcosis (CE). Germinative cell culture of Echinococcus granulosus could be used for anti-echinococcosis agent tests and other biological studies on CE. This study was performed to establish an in vitro cell culture model for E. granulosus germinative cells and to evaluate the lethal effect of Zataria multiflora essential oil (ZMEO) on the cultured cells.

Methods
The inner surface of germinal layers of CE cysts was scraped, and the obtained materials were trypsinized to obtain a suspension of single germinative cells. Medium 199 was used as the basic culture medium and was supplemented with fetal bovine serum, 2-mercaptoethanol, l-cysteine, l-glutamine, glucose, sodium pyruvate, hydatid fluid, amphotericin B and antibiotics. The cells were cultured at a concentration of 104 cells/ml of culture medium and incubated at 37 °C. The culture medium was replaced every 7 days. Chemical composition of ZMEO was identified by GC-MS analysis. ZMEO was tested at concentrations of 0.5–8 mg/ml. Viability of the cells was assessed by trypan blue exclusion assay.

Results
A significant increase in the cell number was evident at 20, 30 and 45 days after cultivation. At 45 days of cultivation, the number of cells was approximately five-fold higher than on the first day. In GC-MC analysis, carvacrol, p-cymene, g-terpinene and thymol were found to be the main compounds of ZMEO. The lethal effect of ZMEO on the germinative cells at concentrations of 6, 7 and 8 mg/ml was 100% after 60, 25 and 7 min of exposure, respectively.

Conclusions
At 45 days of cultivation, the cell concentration was suitable for the desired in vitro experiments. A high lethal effect of ZMEO on the germinative cells of E. granulosus may be considered an opportunity for the introduction of a novel, more effective and safer therapeutic agent for treatment of CE using an herbal product.

Graphical Abstract
MMP-2 is a novel histone H3 N-terminal protease necessary for myogenic gene activation
Authors: Rice Judd C. , Weekley Benjamin H. , Kanholm Tomas , Chen Zhihui , Lee Sunyoung , Fernandez Daniel J. , Abrahamson Rachel , Castaldi Alessandra , Borok Zea , Dynlacht Brian D. , An Woojin 
Published: May 2021

AbstractBackgroundSelective proteolysis of the histone H3 N-terminal tail (H3NT) is frequently observed during eukaryotic development, generating a cleaved histone H3 (H3cl) product within a small, but significant, portion of the genome. Although increasing evidence supports a regulatory role for H3NT proteolysis in gene activation, the nuclear H3NT proteases and the biological significance of H3NT proteolysis remain largely unknown.ResultsIn this study, established cell models of skeletal myogenesis were leveraged to investigate H3NT proteolysis. These cells displayed a rapid and progressive accumulation of a single H3cl product within chromatin during myoblast differentiation. Using conventional approaches, we discovered that the canonical extracellular matrix (ECM) protease, matrix metalloproteinase 2 (MMP-2), is the principal H3NT protease of myoblast differentiation that cleaves H3 between K18-Q19. Gelatin zymography demonstrated progressive increases in nuclear MMP-2 activity, concomitant with H3cl accumulation, during myoblast differentiation. RNAi-mediated depletion of MMP-2 impaired H3NT proteolysis and resulted in defective myogenic gene activation and myoblast differentiation. Supplementation of MMP-2 ECM activity in MMP-2-depleted cells was insufficient to rescue defective H3NT proteolysis and myogenic gene activation.ConclusionsThis study revealed that MMP-2 is a novel H3NT protease and the principal H3NT protease of myoblast differentiation. The results indicate that myogenic signaling induces MMP-2-dependent H3NT proteolysis at early stages of myoblast differentiation. Importantly, the results support the necessity of nuclear MMP-2 H3NT protease activity, independent of MMP-2 activity in the ECM, for myogenic gene activation and proficient myoblast differentiation.
Inverse relationship between serum adenosine deaminase levels and islet beta cell function in patients with type 2 diabetes
Authors: Cao Jie , Wang Hong , Su Jian-bin , Wang Xue-qin , Zhang Dong-mei , Wang Xiao-hua , Liu Wang-shu , Ge Xiao-qin 
Published: May 2021

Abstract
Objective
Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D.

Methods
This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected.

Results
It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = − 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (β =  − 0.125, t =  − 5.397, p < 0.001, adjusted R2 = 0.459).

Conclusions
Serum ADA levels are independently associated with islet beta cell function in patients with T2D.
Are caveolin-1 minor alleles more likely to be risk alleles in insulin resistance mechanisms in metabolic diseases?
Authors: Abaj Faezeh , Saeedy Said Abdul Ghafour , Mirzaei Khadijeh 
Published: May 2021

AbstractObjectivesObesity and insulin resistance (IR) are interrelated in a range of ways. The IR-obesity relationship is not a cause-and-effect association. Molecular biology research has made tremendous strides in discovering contributors to find this association. Genes that control adipocyte function such as caveolin-1 (CAV1);probably interact in the pathogenesis of human IR in this context. The involvement ofCAV1in glucose/lipid homeostasis is revealed and could modify the signaling of the insulin receptor. We examined the association betweenCAV1and insulin signaling in modifying dyslipidemia and fat composition in overweight and obese women with a prevalent variant in theCAV1gene.ResultsMinor allele carriers were slightly older and had higher BMI (p = 0.02), FMI (p = 0.006), and VLF (p = 0.01) values; and tended to have lower total cholesterol TC (p = 0.04), low-density lipoprotein cholesterol (LDL-C) (p = 0.001) and high-density lipoprotein cholesterol (HDL-C) (p = 0.003). HOMA-IR levels predicted fat mass index (FMI) 0.47 (0.08, 0.87), visceral fat level (VFL) 0.65 (0.23, 1.07), TC 6.82 (1.76, 11.88) and HDL-C − 1.663 (− 3.11, − 0.214) only between minor allele carriers in adjusted models. (β, CI). Our results cast a new light on the IR mechanism and future studies will elucidate the clinical relevance ofCAV1-IR in patients with dyslipidemia and high fat composition.
The effects of clonidine and yohimbine in the tail flick and hot plate tests in the naked mole rat (Heterocephalus glaber)
Authors: Mwobobia R. M. , Kanui T. I. , Abelson K. S. P. 
Published: May 2021

Abstract
Objective
The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate the effects of clonidine and yohimbine, an alpha-2 (α2) adrenoceptor agonist and antagonist respectively in the tail flick and hot plate tests.

Results
A significant difference in tail flick latency was noted between saline control and 30 µg/kg clonidine, which was reduced after administration of 30 µg/kg yohimbine. A significant difference in hot plate latency was also noted between saline control and 30 µg/kg clodinine during the periods 30, 45, 60, 75 and 90 min after administration, and between saline control and 10 µg/kg clonidine during 30 min after administration. The hot plate latency by 30 µg/kg clonidine was also reduced by 30 µg/kg yohimbine during 30 min after administration. Since the tail-flick and hot plate tests mediate the effects at spinal and supraspinal levels respectively, the present study indicates the presence and involvement of noradrenergic receptors in thermal antinociception at spinal and supraspinal levels of the NMR, similar to what has been found in other mammals.
Clinical and demographic pattern of chronic granulomatous disease (CGD) from a multicenter perspective: Malaysia’s experience over 26 years
Authors: Noh Lokman Mohd , Latiff Amir Hamzah Abdul , Ismail Intan Hakimah , Noah Rahim Md , Wahab Asrul Abdul , Hamid Intan Juliana Abd. , Ripen Adiratna Mat , Abdullah Nasuruddin B. , Razali Kamarul Azhar , Zainudin Norzila , Bakon Florence , Kok Long Juan , Ali Adli , Aziz Bilkis Banu SAbd , Latif Hasniah Abdul , Mohamad Siti Mardhiana , Zainudeen Zarina Thasneem , Hashim Ilie Fadzilah , Sendut Iean Hamzah , Nadarajaw Thiyagar , Jamil Faizah Mohamed , Ng David C. E. , Abidin Mohd Azri Zainal 
Published: May 2021

Abstract
Background
A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia.

Methods
Data from the Malaysia Primary Immunodeficiency Network (MyPIN) with cases of CGD diagnosed from 1991 until 2016 were collated and analysed.

Results
Twenty patients were diagnosed as CGD. Males (N = 13, 65%) outnumber females (N = 7, 35%). CGD is commonest amongst the Malays (65%) followed by the Chinese (15.0%), Indians (10.0%) and natives of Borneo (10.0%), reflecting the ethnic composition of the country. The mean age of diagnosis was 3.7 years. There was a positive family history in 40% of the cases. Abscess was the main presenting feature in 16 patients (80%) with one involving the brain. Pneumonia occurred in 10 (50%) and one with complicated bronchiectasis. Catalase-positive bacteria were the most commonly isolated pathogen with Chromobacterium violaceum predominating (N = 5, 25%) with consequent high mortality (N = 4, 80%). All CGD patients with C. violaceum infection displayed CD4 + (T helper cells) lymphopenia.

Conclusion
This study has shown CGD occurs in the major ethnic groups of Malaysia. To the best of our knowledge, this is the first and the largest series of chronic granulomatous disease in South East Asia which may be reflective of similar clinical pattern in the region. C. violaceum infection is associated with a higher mortality in CGD patients in Malaysia. All the CGD patients with C. violaceum infection in this patient series displayed CD4 + (T helper) lymphopenia. We recorded rare clinical manifestation of CGD viz. brain abscess and bronchiectasis.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, a mimicker of malignancy: a case report and review of the literature
Authors: Zhuang Eric , Shane Lisa , Ramezan Nima , Ismail Ameera F. , Vora Nilesh L. 
Published: May 2021

Abstract
Background
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a clinically and radiographically distinct inflammatory syndrome affecting multiple structures of the brain, including the cerebellum, brainstem, and spinal cord. The clinical presentation can be variable, including ataxia, nystagmus, dysarthria, dysphagia, and other subacute brainstem, cranial nerve, or cerebellar symptoms. These symptoms can be subacute to chronic, episodic, and progressive, making the diagnosis challenging. The hallmark radiographic magnetic resonance imaging findings are gadolinium-enhancing punctate lesions predominantly “peppering” the pons in a perivascular pattern.

Case presentation
Here, we describe a case and literature review of a 74-year-old Caucasian male who presented with subacute symptoms of ataxia, diplopia, and generalized fatigue. Physical examination was notable for horizontal nystagmus and wide-based gait. Magnetic resonance imaging revealed angiocentric enhancement predominantly in the brainstem and cerebellum, with involvement of the basal ganglia, thalami, and supratentorial white matter. Meanwhile, a screening computed tomography scan demonstrated a right upper lobe mass with biopsy proving primary lung cancer. Biopsy of one of the brain lesions showed perivascular infiltrate primarily composed of CD3+ T cells, scattered CD20+ B cells, and no signs of malignancy. The patient was started on high-dose glucocorticoids followed by a maintenance regimen with rapid improvement clinically and radiographically. Given extensive work-up was negative, these clinical and radiographic findings were consistent with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.

Conclusions
This case illustrates the difficulty of diagnosing chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, given its variable presentation, lack of specific laboratory findings, and poorly understood pathogenesis. We demonstrate a case that responded well to oral corticosteroid burst followed by a taper to the lowest corticosteroid dose clinically possible. Failure to recognize this syndrome could result in permanent central nervous system morbidity. Therefore, earlier recognition is crucial for this treatable condition.
Dynamic thromboembolic left ventricular outflow tract obstruction after aggressive procoagulant treatment in hemorrhagic shock: a case report
Authors: Skrypnikov Vladimir , Rosenthal Christoph , Weber-Carstens Steffen , Menk Mario , Russ Martin 
Published: May 2021

Abstract
Background
In cases of hypertrophic obstructive cardiomyopathy (HOCM), the systolic anterior motion of the mitral valve apparatus results in an obstruction of the left ventricular outflow tract (LVOT), which is known as the SAM [systolic anterior motion] phenomenon. Hypothetically, a pathological obstruction of the LVOT of a different etiology would result in a comparable hemodynamic instability, which would be refractory to inotrope therapy, and may be detectable through echocardiography.

Case presentation
We observed a severely impaired left ventricular function due to a combination of a thrombotic LVOT obstruction and distinctive mitral regurgitation in a 56-year-old Caucasian, female patient after massive transfusion with aggressive procoagulant therapy. Initially, the patient had to be resuscitated due to cardiac arrest after a long-distance flight. The resuscitation attempts in combination with lysis therapy due to suspected pulmonary artery embolism were initially successful but resulted in traumatic liver injury, hemorrhagic shock and subsequent acute respiratory distress syndrome (ARDS). Oxygenation was stabilized with veno-venous extracorporeal membrane oxygenation (ECMO), but the hemodynamic situation deteriorated further. Transesophageal echocardiography (TEE) showed a massive, dynamic LVOT obstruction. Two thrombi were attached to the anterior leaflet of the mitral valve, resulting in a predominantly systolic obstruction. Unfortunately, the patient died of multiple-organ failure despite another round of lysis therapy and escalation of the ECMO circuit to a veno-venoarterial cannulation for hemodynamic support.

Conclusion
Massive transfusion with aggressive procoagulant therapy resulted in mitral valve leaflet thrombosis with dynamic, predominantly systolic LVOT obstruction, comparable to the SAM phenomenon. The pathology was only detectable with a TEE investigation.