bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of breast milk intake volume on early behavioral neurodevelopment of extremely preterm infants
Authors: Gao Ying , Lu Xiaoyu , Pan Mengqing , Liu Chuntian , Min Yuxiao , Chen Xiaochun 
Published: January 2024

Abstract
Background
This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks).

Methods
The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum.

Results
The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups.

Conclusions
Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system.
LeTra: a leaf tracking workflow based on convolutional neural networks and intersection over union
Authors: Jurado-Ruiz Federico , Nguyen Thu-Phuong , Peller Joseph , Aranzana María José , Polder Gerrit , Aarts Mark G. M. 
Published: January 2024

Abstract
Background
The study of plant photosynthesis is essential for productivity and yield. Thanks to the development of high-throughput phenotyping (HTP) facilities, based on chlorophyll fluorescence imaging, photosynthetic traits can be measured in a reliable, reproducible and efficient manner. In most state-of-the-art HTP platforms, these traits are automatedly analyzed at individual plant level, but information at leaf level is often restricted by the use of manual annotation. Automated leaf tracking over time is therefore highly desired. Methods for tracking individual leaves are still uncommon, convoluted, or require large datasets. Hence, applications and libraries with different techniques are required. New phenotyping platforms are initiated now more frequently than ever; however, the application of advanced computer vision techniques, such as convolutional neural networks, is still growing at a slow pace. Here, we provide a method for leaf segmentation and tracking through the fine-tuning of Mask R-CNN and intersection over union as a solution for leaf tracking on top-down images of plants. We also provide datasets and code for training and testing on both detection and tracking of individual leaves, aiming to stimulate the community to expand the current methodologies on this topic.

Results
We tested the results for detection and segmentation on 523 Arabidopsis thaliana leaves at three different stages of development from which we obtained a mean F-score of 0.956 on detection and 0.844 on segmentation overlap through the intersection over union (IoU). On the tracking side, we tested nine different plants with 191 leaves. A total of 161 leaves were tracked without issues, accounting to a total of 84.29% correct tracking, and a Higher Order Tracking Accuracy (HOTA) of 0.846. In our case study, leaf age and leaf order influenced photosynthetic capacity and photosynthetic response to light treatments. Leaf-dependent photosynthesis varies according to the genetic background.

Conclusion
The method provided is robust for leaf tracking on top-down images. Although one of the strong components of the method is the low requirement in training data to achieve a good base result (based on fine-tuning), most of the tracking issues found could be solved by expanding the training dataset for the Mask R-CNN model.
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment
Authors: Zhang Hongying , Liu Yongliang , Liu Jieya , Chen Jinzhu , Wang Jiao , Hua Hui , Jiang Yangfu 
Published: January 2024

AbstractCancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells and angiogenesis, plays a critical role in tumor progression. Cyclic adenosine monophosphate (cAMP) is a second messenger that has pleiotropic effects on the TME. The downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), exchange protein activated by cAMP (EPAC) and ion channels. While cAMP can activate PKA or EPAC and promote cancer cell growth, it can also inhibit cell proliferation and survival in context- and cancer type-dependent manner. Tumor-associated stromal cells, such as CAF and immune cells, can release cytokines and growth factors that either stimulate or inhibit cAMP production within the TME. Recent studies have shown that targeting cAMP signaling in the TME has therapeutic benefits in cancer. Small-molecule agents that inhibit adenylate cyclase and PKA have been shown to inhibit tumor growth. In addition, cAMP-elevating agents, such as forskolin, can not only induce cancer cell death, but also directly inhibit cell proliferation in some cancer types. In this review, we summarize current understanding of cAMP signaling in cancer biology and immunology and discuss the basis for its context-dependent dual role in oncogenesis. Understanding the precise mechanisms by which cAMP and the TME interact in cancer will be critical for the development of effective therapies. Future studies aimed at investigating the cAMP-cancer axis and its regulation in the TME may provide new insights into the underlying mechanisms of tumorigenesis and lead to the development of novel therapeutic strategies.
Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial
Authors: Stoelinga Anna E. C. , Tushuizen Maarten E. , van den Hout Wilbert B. , Girondo Mar D. M. Rodriguez , de Vries Elsemieke S. , Levens Amar D. , Moes Dirk-Jan A. R. , Gevers Tom J. G. , van der Meer Suzanne , Brouwer Hans T. , de Jonge Hendrik J. M. , de Boer Ynte S. , Beuers Ulrich H. W. , van der Meer Adriaan J. , van den Berg Aad P. , Guichelaar Maureen M. J. , Drenth Joost P. H. , van Hoek Bart ,   on behalf of the Dutch Autoimmune Hepatitis Group, Bakker Sjoerd F. , Vrolijk JM , van der Veek Patrick , van Gerven Nicole F. 
Published: January 2024

Abstract
Background
Autoimmune hepatitis (AIH) is a rare, chronic inflammatory disease of the liver. The treatment goal is reaching complete biochemical response (CR), defined as the normalisation of aspartate and alanine aminotransferases and immunoglobulin gamma. Ongoing AIH activity can lead to fibrosis and (decompensated) cirrhosis. Incomplete biochemical response is the most important risk factor for liver transplantation or liver-related mortality. First-line treatment consists of a combination of azathioprine and prednisolone. If CR is not reached, tacrolimus (TAC) or mycophenolate mofetil (MMF) can be used as second-line therapy. Both products are registered for the prevention of graft rejection in solid organ transplant recipients. The aim of this study is to compare the effectiveness and safety of TAC and MMF as second-line treatment for AIH.

Methods
The TAILOR study is a phase IIIB, multicentre, open-label, parallel-group, randomised (1:1) controlled trial performed in large teaching and university hospitals in the Netherlands. We will enrol 86 patients with AIH who have not reached CR after at least 6 months of treatment with first-line therapy. Patients are randomised to TAC (0.07 mg/kg/day initially and adjusted by trough levels) or MMF (max 2000 mg/day), stratified by the presence of cirrhosis at inclusion. The primary endpoint is the difference in the proportion of patients reaching CR after 12 months. Secondary endpoints include the difference in the proportion of patients reaching CR after 6 months, adverse effects, difference in fibrogenesis, quality of life and cost-effectiveness.

Discussion
This is the first randomised controlled trial comparing two second-line therapies for AIH. Currently, second-line treatment is based on retrospective cohort studies. The rarity of AIH is the main issue in clinical research for alternative treatment options. The results of this trial can be implemented in existing international clinical guidelines.

Trial registration
ClinicalTrials.gov NCT05221411. Retrospectively registered on 3 February 2022; EudraCT number 2021–003420-33. Prospectively registered on 16 June 2021.
Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study
Authors: Aggarwal Rohit , Schessl Joachim , Charles-Schoeman Christina , Bata-Csörgő Zsuzsanna , Dimachkie Mazen M. , Griger Zoltan , Moiseev Sergey , Oddis Chester V. , Schiopu Elena , Vencovský Jiri , Beckmann Irene , Clodi Elisabeth , Levine Todd ,   the ProDERM investigators
Published: January 2024

Abstract
Background
Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study.

Methods
ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0–16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16–40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented.

Results
The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4–15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred.

Conclusions
Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors.

Trial registration
ProDERM study (NCT02728752).
Children systemic lupus erythematosus-associated pancreatitis
Authors: Zhang Dan , Lai Jianming , Su Gaixiu , Zhu Jia , Min  , Kang  , Li Ming , Xu Yingjie , Meng Li 
Published: January 2024

Abstract
Objective
To early recognise and improve the prognosis of children systemic lupus erythematosus (cSLE)-associated pancreatitis by summarising and analysing clinical features and prognosis data from 12 cases.

Methods
Retrospective analysis of clinical data from 12 cases of cSLE-associated pancreatitis diagnosed and treated from January 2016 to December 2021 at hospitals such as Children’s Hospital of Capital Institute of Paediatrics.

Results
The median SLEDAI-2K score for disease activity was 18.00 (range 12.25–21.00) in the case group and 10.00 (range 7.00–18.00) in the control group, with a statistically significant difference (P < 0.05) between the two groups. The case group had a higher proportion of abdominal pain, vomiting, abdominal distension, pleural effusion, Raynaud’s phenomenon (RP), splenic infarction, and concurrent macrophage activation syndrome (MAS) than the control group, with a statistically significant difference (P < 0.05). Serum ferritin (SF), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), amylase, and increased 24-h urine protein levels were statistically different between the two groups (P < 0.05); platelet counts (PLT) reduction was also statistically different (P < 0.05). The case group had a higher proportion of methylprednisolone pulse therapy, cyclophosphamide pulse therapy during remission induction, and therapeutic plasma exchange than the control group, with a statistically significant difference (P < 0.05) between the two.

Conclusion
CSLE-associated pancreatitis has a high fatality rate. The presence of RP, splenic infarction, pleural effusion, and MAS warrants attention from clinicians regarding the possibility of pancreatitis. Once pancreatitis is detected, the primary disease needs active treatment for better prognosis.
Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species
Authors: Fang Juntao , Yang Qiangbing , Maas Renée G. C. , Buono Michele , Meijlink Bram , Lotgerink Bruinenberg Dyonne , Benavente Ernest Diez , Mokry Michal , van Mil Alain , Qian Li , Goumans Marie-José , Schiffelers Raymond , Lei Zhiyong , Sluijter Joost P. G. 
Published: January 2024

Abstract
Background
After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge.

Methods
We screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming.

Results
We found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties.

Conclusions
Our findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT.

Graphical abstract
The infimum values of two probability functions for the Gamma distribution
Authors: Sun Ping , Hu Ze-Chun , Sun Wei 
Published: January 2024

AbstractLet α, β be positive real numbers and let $X_{\alpha ,\beta}$

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Knowledge, attitudes and practices towards community-acquired pneumonia and COVID-19 among general population: a cross-sectional study
Authors: Hong Er , Mao Jia , Ke Zhicheng , Tao Wei 
Published: January 2024

Abstract
Background
This study aimed to assess the knowledge, attitudes, and practices (KAP) of the general population to community-acquired pneumonia (CAP) and COVID-19.

Methods
A cross-sectional study was conducted between September 2022 and February 2023, involving the general population from Ningbo Municipal Hospital of Traditional Chinese Medicine with a self-developed questionnaire.

Results
A total of 637 valid questionnaires were collected, with the majority of participants being female (62.48%). The mean score for knowledge, attitudes, and practices were 7.60 ± 2.39 (possible range: 0–12), 43.20 ± 4.57 (possible range: 11–55), and 34.57 ± 4.95 (possible range: 10–50), respectively. Multivariate logistic regression analysis indicated that master’s degree or above (OR = 6.04, 95% CI: 1.80-20.31, P = 0.004) and occupation in business or service careers (OR = 0.28, 95% CI: 0.17–0.48, P < 0.001) were independent associated with knowledge. The knowledge (OR = 1.32, 95%CI: 1.20–1.44, P < 0.001) and female gender (OR = 1.48, 95%CI: 1.03–2.14, P = 0.036) were independently associated with positive attitudes. Attitudes (OR = 1.34, 95%CI: 1.26–1.43, P < 0.001) and a monthly household income greater than 20,000 RMB (OR = 0.31, 95%CI: 0.15–0.64, P = 0.001) were independent associated with practices. Pearson correlation analysis revealed that knowledge positively correlated with attitude scores (r = 0.348, P < 0.001) and practice scores (r = 0.259, P < 0.001), and attitude and practice scores were also positively correlated (r = 0.563, P < 0.001). Structural equation modeling showed that knowledge predicted attitudes (β = 0.67, P < 0.001) and practices (β = 0.17, P = 0.017), while attitudes predicted practices (β = 0.58, P < 0.001).

Conclusion
General population had moderate knowledge, positive attitudes and average practices towards CAP and COVID-19.
The rare Fuegian fox (Lycalopex culpaeus) from the Tierra del Fuego Archipelago: history of discovery, geographic distribution, and socio-ecological aspects
Authors: Jaksic Fabian M. , Zurita Carlos , Briceño Cristóbal , Jiménez Jaime E. 
Published: January 2024

Abstract
Background
The Fuegian fox (Lycalopex culpaeus) is a rare inhabitant of the Tierra del Fuego Archipelago on account of: (a) It is the southernmost Canid in the world. (b) It is the second largest, heaviest, and tallest native Canid in South America. (c) It is currently scarce in northern Tierra del Fuego. (d) It may have been tamed by the Selk’nam natives.

Methods and results
Based on chronicles and scientific reports we document the timeline since discovery of the distinctive and island-confined Fuegian fox. We pay attention to its patchwork distribution within the Fuegian archipelago, with populations spread on the large Tierra del Fuego Island (Fuegia) and on two smaller ones, Hoste and Gable. This fox seems to have disappeared recently from the latter and historic records from Navarino Island are dubious. We provide new distributional records and unpublished photographs. Among the socio-ecological aspects studied, we highlight the relationships of this fox with two local indigenous people: The Yahgan and the Selk´nam.

Discussion
The introduction of sheep Ovis aries in 1885 and the ensuing persecution of its putative predators apparently caused the fox decline from the northern half of Fuegia. The introduction of the continental Chilla fox Lycalopex griseus in 1951 further impacted the Fuegian fox, apparently by competition for food but perhaps also by diseases. It is currently concentrated in the southern half of Tierra del Fuego Island. The possibility that the Selk’nam introduced this fox from the mainland and that they tamed it, is also discussed.
SPiRIT study protocol (Shoulder Pain: Randomised trial of Injectable Treatments): a randomised feasibility and pilot study of autologous protein solution (APS) vs corticosteroids for treating subacromial shoulder pain
Authors: Howard A. , Woods A. , Rombach I. , Achten J. , Appelbe D. , Athwal A. , Jones E. , Draper K. , Gwilym S. 
Published: January 2024

Abstract
Background
The management of subacromial shoulder pain represents a significant challenge and is typically managed through either physiotherapy, joint injection or surgical intervention. Recent surgical trials have questioned the efficacy and there is a need to improve the evidence base for the non-surgical management of this condition.
The study aims to provide evidence of the feasibility of conducting a randomised controlled trial to compare the efficacy of autologous protein solution (APS) against the current standard of care, corticosteroid injection (CSI) for subacromial shoulder pain. Autologous protein solution (APS) is a blood-derived biological injection which has been shown to have anti-inflammatory effects.

Methods
A parallel-group two-arm randomised control trial will be conducted, comparing APS and CSI for shoulder pain. Fifty patients will be recruited. Feasibility will be assessed by examination of the conversion rate of eligible participants to the total number of participants recruited, whether it is possible to collect the appropriate outcome measures and the levels of retention/data compliance at follow-up dates.

Discussion
CSI is the mainstay of conservative management of subacromial shoulder pain. Trials and systematic reviews have reported differing conclusions, but the consensus view is that any benefits seen from CSI use are most likely to be short-term and there remains a significant number of patients who go on to have surgical intervention despite CSI.
Biological injections, such as APS are being increasingly used, in the anticipation they may offer improved longer lasting outcomes for shoulder pain. However, the evidence to demonstrate the comparative efficacy of CSI versus APS does not currently exist. If feasible, a fully powered study will offer clarity to the treatment pathway of thousands of patients each year with subacromial pain.

Trial registration
The study is funded by the National Institute for Health Research–Research for Patient Benefit, NIHR 201473, Trial Registration Number (ISRCTN12536844: SPiRIT. Shoulder pain: randomised trial of injectable treatments–date of Registration 15/9/2021). Protocol Version V1.0_30Jul2021. IRAS Project ID: 294,982.