bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing a very low-carbohydrate adaption of the Diabetes Prevention Program among adults with prediabetes: study protocol for the Lifestyle Education about prediabetes (LEAP) trial
Authors: Griauzde Dina H. , O’Brien Alison , Yancy William S. , Richardson Caroline R. , Krinock Jamie , DeJonckheere Melissa , Isaman Deanna J. M. , Vanias Kaitlyn , Shopinski Samuel , Saslow Laura R. 
Published: September 2022

Abstract
Background
The Center for Disease Control and Prevention’s National Diabetes Prevention Program (NDPP) aims to help individuals with prediabetes avoid progression to type 2 diabetes mellitus (T2DM) through weight loss. Specifically, the NDPP teaches individuals to follow a low-fat, calorie-restricted diet and to engage in regular physical activity to achieve ≥ 5% body weight loss. Most NDPP participants, however, do not achieve this weight loss goal, and glycemic control remains largely unchanged. One promising opportunity to augment the NDPP’s weight loss and glycemic effectiveness may be to teach participants to follow a very low-carbohydrate diet (VLCD), which can directly reduce post-prandial glycemia and facilitate weight loss by reducing circulating insulin and enabling lipolysis. To date, there have been no high-quality, randomized controlled trials to test whether a VLCD can prevent progression to T2DM among individuals with prediabetes. The aim of this study is to test the effectiveness of a VLCD version the NDPP (VLC-NDPP) versus the standard NDPP. We hypothesize the VLC-NDPP will demonstrate greater improvements in weight loss and glycemic control.

Methods
We propose to conduct a 12-month, 1:1, randomized controlled trial that will assign 300 adults with overweight or obesity and prediabetes to either the NDPP or VLC-NDPP. The primary outcome will be glycemic control as measured by change in hemoglobin A1c (HbA1c) from baseline to 12 months. Secondary outcomes will include percent body weight change and changes in glycemic variability, inflammatory markers, lipids, and interim HbA1c. We will evaluate progression to T2DM and initiation of anti-hyperglycemic agents. We will conduct qualitative interviews among a purposive sample of participants to explore barriers to and facilitators of dietary adherence. The principal quantitative analysis will be intent-to-treat using hierarchical linear mixed effects models to assess differences over time.

Discussion
The NDPP is the dominant public health strategy for T2DM prevention. Changing the program’s dietary advice to include a carbohydrate-restricted eating pattern as an alternative option may enhance the program’s effectiveness. If the VLC-NDPP shows promise, this trial would be a precursor to a multi-site trial with incident T2DM as the primary outcome.

Trial registration
NCT05235425. Registered February 11, 2022.
Effects of meditation on physiological and metabolic parameters in patients with type 2 diabetes mellitus “MindDM”: study protocol for a randomized controlled trial
Authors: Dalpatadu K. P. C. , Galappatthy P. , Katulanda P. , Jayasinghe S. 
Published: September 2022

AbstractBackgroundSri Lanka is faced with the challenge of managing a large population with diabetes mellitus by 2030. Psychological stress plays a major role in disease outcome by exerting physiological, psychological and social effects on individuals with chronic disorders.Meditation-based interventions have positive effects on the management of stress and diabetes, which are mediated via modulation of neuro-humoral mechanisms and autonomic functions, among others. Mechanisms of bio-physiological effects of meditation are considered to be through reduction of stress hormones, improvement of insulin resistance and improvement of autonomic dysfunction.MethodsThis study will be conducted as an open-label, randomized controlled clinical trial in the Faculty of Medicine, University of Colombo. The aim is to investigate the effects of meditation on glycaemic control and possible mechanisms of how meditation affects glycaemic control in patients with type 2 diabetes. The study was approved by the Ethics Review Committee of the Faculty of Medicine, University of Colombo (ERC/2019/094). Patients who are attending the professorial unit medical clinic with type 2 diabetes (172 in total) will be recruited based on inclusion-exclusion criteria. Patients who have never meditated or rarely meditated (less than once every three months) will be randomized using block randomization to meditation and waitlisted arms (1:1 allocation ratio). The meditation arm will undergo a mindfulness meditation program (selected after studying several meditation methods) conducted by a qualified instructor weekly for a period of 12 weeks in addition to usual care, while the waitlisted arm will only receive usual care. Daily meditation practices will be recorded in a diary. The primary outcome measure is HbA1c. Secondary outcome measures are fasting blood sugar, fructosamine, insulin resistance (calculated using fasting serum insulin), 24-h urinary cortisol, body mass index, cardiac autonomic reflex testing (Ewing’s battery of tests) and orocecal transit time using hydrogen breath analysis. All these will be done prior to commencement of the intervention and after 3 months in both arms. Data will be analysed using SPSS V-23.DiscussionThis study aims to identify the effect of mindfulness meditation on glycaemic control and the possible mechanisms (neuro humoral and autonomic functions) by which beneficial effects are mediated.Trial registrationRegistered under Sri Lanka Clinical Trial Registry: SLCTR/2021/015The Universal Trial Number (UTN) U1111-1266-8640
The effect of transcranial direct current stimulation combined with working memory training on working memory deficits in schizophrenic patients: study protocol for a randomized controlled trial
Authors: Zhu Xiaolin , Huang Chao , Fan Hongzhen , Fan Fengmei , Zhao Yanli , Xiu Meihong , Wang Yunhui , Li Yajun , Tan Yunlong , Wang Zhiren , Tan Shuping 
Published: September 2022

Abstract
Background
Working memory deficits are one of the core and most characteristic clinical features of cognitive impairment in schizophrenia. Cognitive training can improve the cognitive function of patients with schizophrenia. However, the overall and transfer effects of working memory treatment (WMT) require improvement. Numerous studies have confirmed that transcranial direct current stimulation (tDCS) enhances neuroplasticity in the brain, providing a new treatment approach for cognitive impairment in patients with schizophrenia. We hypothesize that a training mode combining “preheating” (tDCS, which changes the neural activity of working memory-related brain regions) and “ironing” (WMT) affords greater cognitive improvements than WMT alone. In addition, this study aims to examine the mechanisms underlying the superiority of tDCS combined with WMT in improving cognitive function in patients with schizophrenia.

Methods
This study will include 120 patients with schizophrenia aged 18–60 years. The patients will be randomized into four groups: the study group (tDCS + WMT), tDCS group (tDCS + simple response training, SRT), WMT group (sham tDCS + WMT), and control group (sham tDCS + SRT). Patients will receive 20-min, 2 mA sessions of active or sham tDCS twice a day on weekdays for 2 weeks. Each stimulation will be immediately followed by a 1 − 2-min rest and 40 min of WMT or SRT. The primary outcome is cognitive function, measured using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and some subscales of the MATRICS Consensus Cognitive Battery (MCCB). The secondary outcomes are other behavioral measures, variations in brain imaging, and serum levels of brain-derived neurotrophic factor (BDNF). All outcomes will be measured at baseline, post-treatment, and 3-month follow-up, except for brain imaging and BDNF levels, which will be measured at baseline and post-treatment only.

Discussion
If tDCS combined with WMT results in significant improvements and prolonged effects on working memory, this method could be considered as a first-line clinical treatment for schizophrenia. Moreover, these results could provide evidence-based support for the development of other approaches to improve cognitive function in patients with schizophrenia, especially by enhancing WMT effects.

Trial registration
Chictr.org.cn; ChiCTR2200063844. Registered on September 19, 2022.
NAVKIDS2 trial: a multi-centre, waitlisted randomised controlled trial of a patient navigator intervention in children with chronic kidney disease — statistical analysis plan and update to the protocol
Authors: van Zwieten Anita , Ryan Elizabeth G. , Caldwell Patrina , Howard Kirsten , Tong Allison , Craig Jonathan C. , Alexander Stephen I. , Howell Martin , Teixeira-Pinto Armando , Hawley Carmel M. , Jesudason Shilpanjali , Walker Amanda , Mackie Fiona , Kennedy Sean E. , McTaggart Steven , McCarthy Hugh J. , Carter Simon A. , Kim Siah , Woodleigh Reginald , Francis Anna , Mallard Alistair R. , Bernier-Jean Amélie , Johnson David W. , Hahn Deirdre , Reidlinger Donna , Pascoe Elaine , Varghese Julie , Kiriwandeniya Charani , Vergara Liza , Larkins Nicholas , Macauley Luke , Irving Michelle , Khalid Rabia , Guha Chandana , Wong Germaine 
Published: September 2022

Abstract
Background
This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published.

Methods/design
The original protocol was published in BMC Nephrology (https://doi.org/10.1186/s12882-019-1325-y) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1–2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0–16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis.

Trial registration
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213. Prospectively registered on 12 July 2018
Fleas from the Silk Road in Central Asia: identification of Ctenocephalides canis and Ctenocephalides orientis on owned dogs in Uzbekistan using molecular identification and geometric morphometrics
Authors: Deak Georgiana , Safarov Alisher , Xie Xi Carria , Wang Runting , Mihalca Andrei Daniel , Šlapeta Jan 
Published: September 2022

AbstractBackgroundThe Silk Road connected the East and West for over 1500 years. Countries in Central Asia are valuable in addressing the hypothesis that parasites on domestic animals were introduced along the Silk Road. Adult fleas are obligate parasites, having worldwide distribution. In dogs,Ctenocephalides canis,C. felisandC. orientisare the most common species identified. The distribution of the Oriental cat flea,C. orientis, is restricted to southeast Asia. The purpose of this study was to determine the diversity of dog fleas from Uzbekistan, a country in Central Asia, with particular reference toC. orientis.MethodsFleas were collected from 77 dogs from 5 locations in Uzbekistan. Thecox1gene sequences fromCtenocephalidesspp. were compared to global collection ofCtenocephalides cox1haplotypes. Landmark-based geometric morphometrics have been applied to the head and curvature to compareC. canisandC. canisusing canonical variate analysis and discriminant function analysis.ResultsOverall, 199 fleas were collected and identified asC. canis(n = 115, 58%),C. orientis(n = 53, 27%) andPulex irritans(n = 22, 11%). None of the fleas wereC. felis. AllCtenocephalidesspp. fleas were subject tocox1amplification and 95% (166/175) yielded DNA sequence. There were 25cox1haplotypes; 14 (22/25, 88%) wereC. canis cox1haplotypes and 3 (3/25, 12%) wereC. orientis cox1haplotypes. Molecular analysis confirmed the absence ofC. felis. Four (4/22) and one (1/3)cox1haplotypes were identical tocox1haplotypes belonging toC. canisandC. orientis cox1haplotypes identified elsewhere, respectively. Overall morphometric analysis confirmed significant differences between the head shape ofC. canisandC. orientisand improved four–fivefold the species identification compared to traditional morphological key.ConclusionWe report for the first time the presence ofC. orientisin Uzbekistan. Differentiation ofC. orientisfromC. canisandC. felisremains difficult in regions where these species coexist. Studies in Central and Southeast Asia should confirm species identity usingcox1locus to enable retracing of the distribution of theCtenocephalidesin Asia. The presence ofC. orientissuggests that this species may have been introduced from the east along the ancient Silk Road.Graphical Abstract
Whipworm secretions and their roles in host-parasite interactions
Authors: Shears Rebecca K. , Grencis Richard K. 
Published: September 2022

AbstractWhipworm (Trichuris) is a genus of roundworms that causes gastrointestinal infections in humans and animals. Of particular interest are T. trichiura, the causative agent of human trichuriasis, a neglected tropical disease that affects 477 million people worldwide, and T. suis, the pig whipworm species, responsible for growth stunting and economic losses within the agricultural industry. The naturally occurring mouse whipworm, T. muris, has been used for decades as a model for trichuriasis, yielding knowledge on the biology of these parasites and the host response to infection. Ex vivo culture of T. muris (and to some extent, T. suis) has provided insight into the composition of the excretory/secretory (E/S) products released by worms, which include a myriad of proteins, RNAs, lipids, glycans, metabolites and extracellular vesicles. T. muris E/S has formed the basis of the search for whipworm vaccine candidates, while the immunomodulatory potential of T. suis and T. muris secretions has been investigated with the aim of improving our understanding of how these parasites modulate host immunity, as well as identifying immunomodulatory candidates with therapeutic potential in the context of inflammatory diseases. This article will review the various components found within Trichuris E/S, their potential as vaccine candidates and their immunomodulatory properties.
Graphical Abstract
Dorso-ventral osteophytes of interphalangeal joints correlate with cartilage damage and synovial inflammation in hand osteoarthritis: a histological/radiographical study
Authors: Sunk Ilse-Gerlinde , Amoyo-Minar Love , Niederreiter Birgit , Soleiman Afschin , Kainberger Franz , Smolen Josef S. , Aletaha Daniel , Bobacz Klaus 
Published: September 2022

Abstract
Objective
To detect dorsally located osteophytes (OP) on lateral x-ray views and to correlate their presence with the extent of structural joint damage, determined by histologic grading (cartilage damage and synovial inflammation) and radiographic scoring in hand osteoarthritis (HOA).

Methods
Distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints were obtained from post mortem specimens (n = 40). Multiplanar plain x-rays were taken (dorso/palmar (dp) and lateral views). Radiographic OA was determined by the Kellgren and Lawrence classification. Joint samples were prepared for histological analysis and cartilage damage was graded according to the Mankin scoring system. Inflammatory changes of the synovial membrane were scored using the general synovitis score (GSS). Spearman’s correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups were determined by Mann-Whitney test.

Results
Bony proliferations that were only detectable on lateral views but reminiscent of OPs on dp images were termed dorso-ventral osteophytes (dvOPs). All joints displaying dvOPs were classified as OA and the presence of dvOPs in DIP and PIP joints correlated with the extent of histological and radiographic joint damage, as well as with patient age. Joint damage in osteoarthritic DIP and PIP joints without any dvOPs was less severe compared to joints with dvOPs. Synovial inflammation was mainly present in joints displaying dvOPs and correlated with joint damage.

Conclusion
dvOPs are associated with increasing structural alterations in DIP and PIP joints and can be seen as markers of advanced joint damage. Detecting dvOPs can facilitate the diagnosis process and improve damage estimation in HOA.
Panhypopituitarism as the first sign of paraneoplastic limbic encephalitis in a patient with cured testicular cancer: a case report
Authors: Lei Yvonne , Glaeser Alexandra Milin 
Published: September 2022

Abstract
Background
Paraneoplastic limbic encephalitis is a rare neurologic syndrome that affects patients with cancer and commonly presents with symptoms of personality changes, visual disturbances, seizures, vertigo, and memory loss. It has an immune-mediated pathophysiology and is associated with antibodies directed against both the tumor and limbic structures in the nervous system. Here, we report a case of paraneoplastic limbic encephalitis with an unusual presentation with initial symptoms of panhypopituitarism.

Case presentation
A 28-year-old Caucasian man with history of testicular cancer in remission for almost 2 years was admitted to our hospital for altered mental status, syncope, vertical gaze palsy, ataxia, and tremor. Three months prior to admission, he began to have initial symptoms of fatigue, weight gain, and hypogonadism. A few weeks before admission, he also developed worsening neurological symptoms that led him to present to the hospital. While hospitalized, he had an episode of syncope. Evaluation of his syncope revealed that he was hypovolemic due to polyuria, concerning for diabetes insipidus. While the patient did not meet criteria for diabetes insipidus, further endocrine laboratory testing to evaluate his central hormonal axes revealed panhypopituitarism. He also underwent a neurologic work-up with brain magnetic resonance imaging and lumbar puncture, with results consistent with encephalitis. He received high-dose steroids, plasmapheresis, and intravenous immunoglobulin, which did not significantly improve his physical examination or mental status. Extensive testing did not show any recurrence of his testicular cancer. Paraneoplastic antibodies were also ordered, with anti-Ma2 antibodies eventually returning positive, consistent with anti-Ma2 paraneoplastic limbic encephalitis.

Conclusion
Paraneoplastic limbic encephalitis is often a difficult diagnosis due to its variable presentation and timeline of presentation, leading to delays in both diagnosis and treatment. While paraneoplastic limbic encephalitis usually presents with neurological symptoms, it may also present with panhypopituitarism. A high index of suspicion is warranted for paraneoplastic syndromes in patients with history of malignancy, even if the malignancy is in remission.
Acute pancreatitis in pregnancy following COVID-19 vaccine: a case report
Authors: Dey Rajib Kumar , Ilango Hemamala , Bhatta Subash , Shaheed Ahmed , Dole Shanaz , Zooshan Ahmed , Faisham Mohamed , Murad Moosa 
Published: September 2022

Abstract
Background
Since the approval of the Pfizer–BioNTech (BNT162b2) mRNA vaccine for COVID-19 infection, a few adverse effects have been reported. Acute pancreatitis has been reported in a few patients. However, there is currently no research showing a direct relationship between the vaccine and acute pancreatitis. Here, we report a case of acute pancreatitis following Pfizer vaccination in a young healthy pregnant woman without any known risk factors. To our knowledge, this is the first case report of possible vaccine-induced pancreatitis in a pregnant woman.

Case presentation
The patient, a 24-year-old South-Asian female, at 31 weeks of gestation, presented with severe epigastric pain radiating to the back and worsening on lying supine, associated with nausea and vomiting. She was diagnosed with acute pancreatitis with a serum lipase level of 4376 U/L and an ultrasound showing features of pancreatitis. The patient received her first dose of the Pfizer vaccine 1 week prior to these symptoms. Detailed evaluation did not show any etiological cause of pancreatitis. The patient had a spontaneous vaginal delivery and the baby was shifted to the neonatal intensive care unit in a stable condition. A computed tomography scan postpartum (day 2) demonstrated acute interstitial edematous pancreatitis. The patient was managed conservatively in the intensive care unit and discharged home in a stable condition.

Conclusion
This report highlights the importance of a detailed history and evaluation, and the close monitoring of any patient presenting with abdominal pain after vaccination. Acute pancreatitis can be fatal if not picked up early.
Associations of habitual glucosamine supplementation with incident gout: a large population based cohort study
Authors: Liu Mengyi , Ye Ziliang , Zhang Yanjun , Yang Sisi , Wu Qimeng , Zhou Chun , He Panpan , Zhang Yuanyuan , Gan Xiaoqin , Qin Xianhui 
Published: September 2022

Abstract
Objectives
The association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population.

Methods
A total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data.

Results
At baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71–0.92), but not in males (HR, 1.05, 95% CI, 0.97–1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50–0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77–1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183).

Conclusions
Habitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males.