bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transdisciplinarity of India’s master’s level public health programmes: evidence from admission criteria of the programmes offered since 1995
Authors: Ilangovan Kumaravel , Muthappan Sendhilkumar , Govindarajan Keerthiga , Vairamani Vignesh , Venkatasamy Vettrichelvan , Ponnaiah Manickam 
Published: February 2022

AbstractIntroductionIn the Indian subcontinent, Master’s-level Public Health (MlPH) programmes attract graduates of diverse academic disciplines from health and non-health sciences alike. Considering the current and futuristic importance of the public health cadre, we described them and reviewed their transdisciplinarity status based on MlPH admissibility criteria 1995 to 2021.MethodsUsing a search strategy, we abstracted information available in the public domain on MlPH programmes and their admissibility criteria. We categorized the admission criteria based on specified disciplines into Health science, Non-health science and Non-health non-science categories. We described the MlPH programmes by location, type of institution, course duration, curriculum, pedagogical methods, specializations offered, and nature of admission criteria statements. We calculated descriptive statistics for eligible educational qualifications for MlPH admission.ResultsOverall, 76 Indian institutions (Medical colleges—21 and Non-medical coleges—55) offered 92 MlPH programmes (Private—58 and Public—34). We included 89 for review. These programmes represent a 51% increase (n = 47) from 2016 to 2021. They are mostly concentrated in 21 Indian provinces. These programmes stated that they admit candidates of but not limited to “graduation in any life sciences”, “3-year bachelor’s degree in any discipline”, “graduation from any Indian universities”, and “graduation in any discipline”. Among the health science disciplines, Modern medicine (n = 89; 100%), Occupational therapy (n = 57; 64%) is the least eligible. Among the non-health science disciplines, life sciences and behavioural sciences (n = 53; 59%) and non-health non-science disciplines, humanities and social sciences (n = 62; 72%) are the topmost eligible disciplines for admission in the MPH programmes.ConclusionOur review suggests that India’s MlPH programmes are less transdisciplinary. Relatively, non-medical institutions offer admission to various academic disciplines than the medical institutions in their MlPH programmes. India’s Master’s level public health programmes could be more inclusive by opening to graduates from trans-disciplinary backgrounds.
Effects of high-intensity interval training on improving arterial stiffness in Chinese female university students with normal weight obese: a pilot randomized controlled trial
Authors: Hu Jingyun , Liu Min , Yang Ruoyu , Wang Liyan , Liang Leichao , Yang Yuanyuan , Jia Shihao , Chen Ruiyi , Liu Qianle , Ren Yu , Zhu Lei , Cai Ming 
Published: February 2022

Abstract
Background
High intensity interval training (HIIT) has been reported to exert better effects on cardiovascular fitness in obesity, but little known about the arterial stiffness (AS) in female university students with normal weight obesity (NWO). Thus, this study aimed to investigate the effects of HIIT on the body composition, heart rate (HR), blood pressure (BP), blood lipids metabolism as well as the novel parameters of propensity for AS (arterial velocity pulse index [AVI], arterial pressure volume index [API]) for female university students with NWO.

Methods
Forty female university students with NWO were randomly assigned to control group (n = 20) and HIIT group (3 bouts of 9‑min intervals at 90% of the maximal heart rate [HRmax], interspersed by 1 min rest, 5 days a week, n = 20). Tests were performed before and after 4 weeks of training. Repeated measures ANOVA and simple effect test analysis were used to analyze dependent variable changes.

Results
After 4 weeks HIIT statistically significantly improved the body composition by decreasing the body mass index, body fat percent, total body fat mass (BFM), BFM of left arm, measured circumference of left arm, and obesity degree, and increasing the total body skeletal muscle mass, protein content, total body water, fat free mass, body cell mas, and InBody score. HIIT also statistically significantly decreased the HR and BP. As for the lipid profile, HIIT obviously ameliorated the blood lipids metabolism by decreasing the levels of total cholesterol (TC), triglyceride, low-density lipoprotein, and TC/HDL, and increasing the levels of high-density lipoprotein (HDL). In addition, the AVI and API were markedly decreased via HIIT intervention.

Conclusions
HIIT produced significant and meaningful benefits for body composition, HR, BP, and blood lipids metabolism, and could decrease AS in female university students with NWO. This suggests that HIIT may effectively reduce the risk of arteriosclerosis and protect the cardiovascular function for female university students with NWO.
Trial registration ChiCTR2100050711. Registered 3 September 2021. Retrospectively registered.
Catch-up growth of infants born to mothers with autoimmune rheumatic disorders
Authors: Sim Soo Yeun , Choi Hye Yeon , Jung Min Ho , Lee Soo Young , Rhim Jung Woo , Kang Hyun Mi , Jeong Dae Chul 
Published: February 2022

Abstract
Background
In women with autoimmune rheumatic disorders (ARD), pregnancy complications or postpartum events are more frequent compared to the general population. Transplacental autoantibodies or cytokines influence various fetal and neonatal outcomes. We compared the growth patterns of babies born to mothers with ARD versus healthy mothers to assess the long-term growth outcomes of children born to women with ARD.

Methods
This was a retrospective age-matched cohort analyses of babies born to mothers with ARD from the hospitals belonging to the Catholic University of Korea between 2010 and 2017. Demographic and autoimmune laboratory test data of the mothers and newborns were assessed. Neonatal growth was measured in terms of height and weight, measured at birth and follow-up examinations.

Results
We enrolled 142 infants from mothers with ARD and 149 infants from healthy mothers. There was no significant difference between mothers with ARD and healthy mothers in terms of delivery age, parity, abortion, and premature delivery history. The mothers with ARD were diagnosed with systemic lupus erythematosus (81%), Sjogren syndrome (6%), and other autoimmune phenomena (11%). The groups were significantly different in terms of neonatal characteristics such as prematurity, gestational age, birth weight, and height, but not in Apgar score and delivery type. For most neonates, autoimmune laboratory results were normalized within 1 year, except for anti-La/SSB antibody, which remained high in some. The height and weight for age z-score were lower than the normal age groups at birth but showed catch-up growth by 2 years of age.

Conclusions
Low birthweight and prematurity at birth for neonates born to mothers with ARD could be caught up by 2 years of age, and maternal ARD does not affect the growth of their offspring.
Cyclic multiplex fluorescent immunohistochemistry and machine learning reveal distinct states of astrocytes and microglia in normal aging and Alzheimer’s disease
Authors: Muñoz-Castro Clara , Noori Ayush , Magdamo Colin G. , Li Zhaozhi , Marks Jordan D. , Frosch Matthew P. , Das Sudeshna , Hyman Bradley T. , Serrano-Pozo Alberto 
Published: February 2022

Abstract
Background
Astrocytes and microglia react to Aβ plaques, neurofibrillary tangles, and neurodegeneration in the Alzheimer’s disease (AD) brain. Single-nuclei and single-cell RNA-seq have revealed multiple states or subpopulations of these glial cells but lack spatial information. We have developed a methodology of cyclic multiplex fluorescent immunohistochemistry on human postmortem brains and image analysis that enables a comprehensive morphological quantitative characterization of astrocytes and microglia in the context of their spatial relationships with plaques and tangles.

Methods
Single FFPE sections from the temporal association cortex of control and AD subjects were subjected to 8 cycles of multiplex fluorescent immunohistochemistry, including 7 astroglial, 6 microglial, 1 neuronal, Aβ, and phospho-tau markers. Our analysis pipeline consisted of: (1) image alignment across cycles; (2) background subtraction; (3) manual annotation of 5172 ALDH1L1+ astrocytic and 6226 IBA1+ microglial profiles; (4) local thresholding and segmentation of profiles; (5) machine learning on marker intensity data; and (6) deep learning on image features.

Results
Spectral clustering identified three phenotypes of astrocytes and microglia, which we termed “homeostatic,” “intermediate,” and “reactive.” Reactive and, to a lesser extent, intermediate astrocytes and microglia were closely associated with AD pathology (≤ 50 µm). Compared to homeostatic, reactive astrocytes contained substantially higher GFAP and YKL-40, modestly elevated vimentin and TSPO as well as EAAT1, and reduced GS. Intermediate astrocytes had markedly increased EAAT2, moderately increased GS, and intermediate GFAP and YKL-40 levels. Relative to homeostatic, reactive microglia showed increased expression of all markers (CD68, ferritin, MHC2, TMEM119, TSPO), whereas intermediate microglia exhibited increased ferritin and TMEM119 as well as intermediate CD68 levels. Machine learning models applied on either high-plex signal intensity data (gradient boosting machines) or directly on image features (convolutional neural networks) accurately discriminated control vs. AD diagnoses at the single-cell level.

Conclusions
Cyclic multiplex fluorescent immunohistochemistry combined with machine learning models holds promise to advance our understanding of the complexity and heterogeneity of glial responses as well as inform transcriptomics studies. Three distinct phenotypes emerged with our combination of markers, thus expanding the classic binary “homeostatic vs. reactive” classification to a third state, which could represent “transitional” or “resilient” glia.
Growth rate of ascending thoracic aortic aneurysms in a non-referral-based population
Authors: Weininger Gabe , Mori Makoto , Yousef Sameh , Hur David J. , Assi Roland , Geirsson Arnar , Vallabhajosyula Prashanth 
Published: February 2022

Abstract
Background
Prior studies on ascending thoracic aortic aneurysm (ATAA) growth rates have reported approximately 1 mm of growth per year but these studies are based on referral-based study populations which are biased towards the highest risk patients who may not represent the true natural history of aortic aneurysm disease. We aimed to characterize the growth rate of ATAAs in a non-referral-based population, using a large institutional database of computed tomography (CT) scans.

Methods
We queried the 21,325 CT scans performed at our institution between 2013 and 2016 on patients ages 50–85 years old for radiologic diagnosis of aortic aneurysm or dilatation. 560 patients were identified to have aortic dilatation > 4 cm, of which 207 had follow-up scan intervals > 6 months. This comprised our non-referral-based study population. Linearized annual aneurysm growth rates were calculated by dividing the change in aortic size by the time interval between CT scans.

Results
The median time interval between scans was 2.7 years (interquartile range [IQR] 1.5–4.2) for the 207 patients included in the study. The median initial aneurysm size was 4.3 cm (IQR 4.1–4.5). 38.2% (n = 79) of patients did not experience aortic dilatation. The median growth rate was 0.13 mm/year (IQR − 0.24 to 0.49). Of patients in the top quartile of growth rates, 26.9% of patients were female whereas 12.9% of patients were female in the bottom three quartiles of growth rates.

Conclusion
While some patients’ ATAAs may grow at previously published rates of around 1 mm/year, this is not the predominant pattern in a non-referral-based population and may over-estimate the overall growth rate of ATAAs.
Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study
Authors: Mighiu Claudia , O’Hara Sonia , Ferri Grazzi Enrico , Murray Karen F. , Schattenberg Jörn M. , Ventura Emily , Karakaidos Melanie , Taylor Alison , Brrang Harpreet , Dhawan Anil , Willemse Jose , Finnegan Alan 
Published: February 2022

Abstract
Background
Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included.

Results
The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30–49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient’s PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days).

Conclusions
The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances.
Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists
Authors: Kalantari Silvia , Brezzi Brigida , Bracciamà Valeria , Barreca Antonella , Nozza Paolo , Vaisitti Tiziana , Amoroso Antonio , Deaglio Silvia , Manganaro Marco , Porta Francesco , Spada Marco 
Published: February 2022

Abstract
Background
Methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) is the most common disorder of cobalamin intracellular metabolism, an autosomal recessive disease, whose biochemical hallmarks are hyperhomocysteinemia, methylmalonic aciduria and low plasma methionine. Despite being a well-recognized disease for pediatricians, there is scarce awareness of its adult presentation. A thorough analysis and discussion of cobalamin C defect presentation in adult patients has never been extensively performed. This article reviews the published data and adds a new case of the latest onset of symptoms ever described for the disease.

Results
We present the emblematic case of a 45-year-old male, describing the diagnostic odyssey he ventured through to get to the appropriate treatment and molecular diagnosis. Furthermore, available clinical, biochemical and molecular data from 22 reports on cases and case series were collected, resulting in 45 adult-onset CblC cases, including our own. We describe the onset of the disease in adulthood, encompassing neurological, psychiatric, renal, ophthalmic and thromboembolic symptoms. In all cases treatment with intramuscular hydroxycobalamin was effective in reversing symptoms. From a molecular point of view adult patients are usually compound heterozygous carriers of a truncating and a non-truncating variant in the MMACHC gene.

Conclusion
Adult onset CblC disease is a rare disorder whose diagnosis can be delayed due to poor awareness regarding its presenting insidious symptoms and biochemical hallmarks. To avoid misdiagnosis, we suggest that adult onset CblC deficiency is acknowledged as a separate entity from pediatric late onset cases, and that the disease is considered in the differential diagnosis in adult patients with atypical hemolytic uremic syndromes and/or slow unexplained decline in renal function and/or idiopathic neuropathies, spinal cord degenerations, ataxias and/or recurrent thrombosis and/or visual field defects, maculopathy and optic disc atrophy. Plasma homocysteine measurement should be the first line for differential diagnosis when the disease is suspected. To further aid diagnosis, it is important that genes belonging to the intracellular cobalamin pathway are included within gene panels routinely tested for atypical hemolytic uremic syndrome and chronic kidney disorders.
Seroprevalence of Encephalitozoon cuniculi and Toxoplasma gondii antibodies and risk-factor assessment for Encephalitozoon cuniculi seroprevalence in Finnish pet rabbits (Oryctolagus cuniculus)
Authors: Mäkitaipale Johanna , Järvenpää Emmi , Bruce Anne , Sankari Satu , Virtala Anna-Maija , Näreaho Anu 
Published: February 2022

Abstract
Background
Neurological signs, such as head tilt, torticollis, paralysis, and seizures, are common in rabbits. Differential diagnoses include two zoonotic infections caused by the microsporidial fungi Encephalitozoon cuniculi and the apicomplexan protozoa Toxoplasma gondii. Both infections are mainly latent in rabbits but may cause severe or even fatal disease. Although several international studies have reported the seroprevalence of these pathogens in different commercial rabbit populations, similar prevalence studies and risk-factor analyses among family-owned pet rabbits are uncommon and lacking in Scandinavia. We sought to estimate the seroprevalence and possible risk factors for E. cuniculi and T. gondii among Finnish pet rabbits. We used ELISA to measure E. cuniculi IgG seroprevalence of 247 rabbits and modified direct agglutination test for T. gondii seroprevalence of 270 rabbits. Samples were collected as part of the Finnish Pet Rabbit Health Research project. Internet-based questionnaires (n = 231) completed by the rabbit owners were used for risk-factor analysis.

Results
The apparent seroprevalence of E. cuniculi was 29.2% and true seroprevalence of T. gondii 3.9%. Risk factors were analysed only for E. cuniculi due to the low T. gondii seroprevalence. The final multivariable logistic regression model revealed that rabbits spending the whole summer outdoors had a higher risk of being E. cuniculi seropositive than rabbits with limited outdoor access. Additionally, rabbits living in households with only one or two rabbits had higher risk of being E. cuniculi seropositive than those in multi-rabbit households.

Conclusions
Nearly one third of Finnish pet rabbits participating in this study had E. cuniculi IgG antibodies, indicating previous exposure to this pathogen. The prevalence is similar to that reported previously in clinically healthy rabbit populations in UK and Korea. While the seroprevalence of T. gondii was low (3.9%), antibodies were detected. Therefore, these zoonotic parasitic infections should be considered as differential diagnoses when treating rabbits.
Autophagic Schwann cells promote perineural invasion mediated by the NGF/ATG7 paracrine pathway in pancreatic cancer
Authors: Zhang Wunai , He Rui , Yang Wenbin , Zhang Yan , Yuan Qinggong , Wang Jixin , Liu Yang , Chen Shuo , Zhang Simei , Zhang Weifan , Zhu Zeen , Zhang Jing , Wang Zheng , Li Junhui 
Published: February 2022

Abstract
Background
Perineural invasion (PNI) and autophagy are two common features in the tumor microenvironment of pancreatic cancer (PanCa) and have a negative effect on prognosis. Potential mediator cells and the molecular mechanism underlying their relationships need to be fully elucidated.

Methods
To investigate the autophagy of Schwann cells (SCs) in PNI, we reproduced the microenvironment of PNI by collecting clinical PNI tissue, performing sciatic nerve injection of nude mice with cancer cells and establishing a Dorsal root ganglion (DRG) coculture system with cancer cell lines. Autophagy was detected by IHC, IF, transmission electron microscopy (TEM) and western blotting assays. Apoptosis was detected by IF, TEM and western blotting. NGF targeting molecular RO 08–2750(RO) and the autophagy inhibitor Chloroquine (CQ) were utilized to evaluate the effect on autophagy and apoptosis in SCs and PanCa cells in PNI samples.

Results
SC autophagy is activated in PNI by paracrine NGF from PanCa cells. Autophagy-activated Schwann cells promote PNI through a) enhanced migration and axon guidance toward PanCa cells and b) increased chemoattraction to PanCa cells. The NGF-targeting reagent RO and autophagy inhibitor CQ inhibited Schwann cell autophagic flux and induced Schwann cell apoptosis. Moreover, RO and CQ could induce PanCa cell apoptosis and showed good therapeutic effects in the PNI model.

Conclusions
PanCa cells can induce autophagy in SCs through paracrine pathways such as the NGF/ATG7 pathway. Autophagic SCs exert a “nerve-repair like effect”, induce a high level of autophagy of cancer cells, provide a “beacon” for the invasion of cancer cells to nerve fibers, and induce directional growth of cancer cells. Targeting NGF and autophagy for PNI treatment can block nerve infiltration and is expected to provide new directions and an experimental basis for the research and treatment of nerve infiltration in pancreatic cancer.
Efficacy and safety of Qushi Huayu granule for hyperlipidemia: study protocol for a randomized, double-blind, placebo-controlled trial
Authors: Sun Yuanlong , Hu Na , Chen Gaofeng , Wang Yanjie , Hu Yiyang , Ge Maojun , Zhao Yu 
Published: February 2022

Abstract
Background
Hyperlipidemia has become a common chronic disease worldwide in recent years. Studies have shown that hyperlipidemia patients, especially those with a high level of serum low-density lipoprotein cholesterol (LDL-C), have a significantly higher prevalence of atherosclerosis, leading to coronary heart disease. Previous basic experiments and clinical studies have shown that Qushi Huayu granules (QSHY) reduce blood lipids in patients with non-alcoholic fatty liver disease (NAFLD) accompanied by hyperlipidemia. However, the clinical efficacy of QSHY in patients with hyperlipidemia is still lacking. This study aims to investigate the effect and safety of QSHY for hyperlipidemia.

Methods
This is a randomized, double-blind, placebo-controlled trial. A total of 210 participants will be enrolled and randomized into the QSHY or placebo granules groups in equal proportions, who will receive treatment for 24 weeks. The primary outcome will be the change in LDL-C from baseline to week 12. Secondary outcomes will be changes in other serum lipids markers, life quality measuring health surveys, and traditional Chinese medicine (TCM) pattern scale. All related tests will be measured at baseline, week 12, and week 24 after enrollment. Adverse events and the safety of intervention will be monitored and evaluated.

Discussion
We designed a clinical trial of hyperlipidemia management with QSHY, a TCM prescription. The results of this trial will present the efficacy and safety of QSHY in patients with hyperlipidemia.

Trial registration
Chinese Clinical Trial Registry ChiCTR2000034125. Registered on June 25, 2019