bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal malrotation in a female newborn affected by Osteopathia Striata with Cranial Sclerosis due to a de novo heterozygous nonsense mutation of the AMER1 gene
Authors: Serra Gregorio , Antona Vincenzo , Di Pace Maria Rita , Giuffrè Mario , Morgante Giusy , Piro Ettore , Pirrello Roberto , Salerno Sergio , Schierz Ingrid Anne Mandy , Verde Vincenzo , Corsello Giovanni 
Published: December 2022

AbstractBackgroundOsteopathia Striata with Cranial Sclerosis (OS-CS), also known as Horan-Beighton Syndrome, is a rare genetic disease; about 90 cases have been reported to date. It is associated with mutations (heterozygous for female subjects and hemizygous for males) of theAMER1gene, located at Xq11.2, and shows an X-linked pattern of transmission. Typical clinical manifestations include macrocephaly, characteristic facial features (frontal bossing, epicanthal folds, hypertelorism, depressed nasal bridge, orofacial cleft, prominent jaw), hearing loss and developmental delay. Males usually present a more severe phenotype than females and rarely survive. Diagnostic suspicion is based on clinical signs, radiographic findings of cranial and long bones sclerosis and metaphyseal striations, subsequent genetic testing may confirm it.Case presentationHereby, we report on a female newborn with frontal and parietal bossing, narrow bitemporal diameter, dysplastic,low-set and posteriorly rotated ears, microretrognathia, cleft palate, and rhizomelic shortening of lower limbs. Postnatally, she manifested feeding intolerance with biliary vomiting and abdominal distension. Therefore, in the suspicion of bowel obstruction, she underwent surgery, which evidenced and corrected an intestinal malrotation. Limbs X-ray and skull computed tomography investigations did not show cranial sclerosis and/or metaphyseal striations. Array-CGH analysis revealed normal findings. Then, a target next generation sequencing (NGS) analysis, including the genes involved in skeletal dysplasias, was performed and revealed ade novoheterozygous nonsense mutation of theAMER1gene. The patient was discharged at 2 months of age and included in a multidisciplinary follow-up. Aged 9 months, she now shows developmental and growth (except for relative macrocephaly) delay. The surgical correction of cleft palate has been planned.ConclusionsOur report shows the uncommon association of intestinal malrotation in a female newborn with OS-CS. It highlights that neonatologists have to consider such a diagnosis, even in absence of cranial sclerosis and long bones striations, as these usually appear over time. Other syndromes with cranial malformations and skeletal dysplasia must be included in the differential diagnosis. The phenotypic spectrum is wide and variable in both genders. Due to variable X-inactivation, females may also show a severe and early-onset clinical picture. Multidisciplinary management and careful, early and long-term follow-up should be offered to these patients, in order to promptly identify any associated morbidities and prevent possible complications or adverse outcomes.
Towards resolution of the intron retention paradox in breast cancer
Authors: Shah Jaynish S. , Milevskiy Michael J. G. , Petrova Veronika , Au Amy Y. M. , Wong Justin J. L. , Visvader Jane E. , Schmitz Ulf , Rasko John E. J. 
Published: December 2022

Abstract
Background
After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR, and such patterns have been pursued as both biomarkers and therapeutic targets. Paradoxically, breast cancer (BrCa) is the only tumour type in which IR is reduced compared to adjacent normal breast tissue.

Methods
In this study, we have conducted a pan-cancer analysis of IR with emphasis on BrCa and its subtypes. We explored mechanisms that could cause aberrant and pathological IR and clarified why normal breast tissue has unusually high IR.

Results
Strikingly, we found that aberrantly decreasing IR in BrCa can be largely attributed to normal breast tissue having the highest occurrence of IR events compared to other healthy tissues. Our analyses suggest that low numbers of IR events in breast tumours are associated with poor prognosis, particularly in the luminal B subtype. Interestingly, we found that IR frequencies negatively correlate with cell proliferation in BrCa cells, i.e. rapidly dividing tumour cells have the lowest number of IR events. Aberrant RNA-binding protein expression and changes in tissue composition are among the causes of aberrantly decreasing IR in BrCa.

Conclusions
Our results suggest that IR should be considered for therapeutic manipulation in BrCa patients with aberrantly low IR levels and that further work is needed to understand the cause and impact of high IR in other tumour types.
A protocol for a randomized clinical trial assessing the efficacy of hypertonic dextrose injection (prolotherapy) in chronic ankle instability
Authors: Sit Regina Wing Shan , Wu Ricky Wing Keung , Ling Samuel Ka Kin , Wang Bo , Chan Dicken Cheong Chun , Yip Benjamin Hon Kei , Wong Samuel Yeung Shan , Reeves Kenneth Dean , Rabago David 
Published: December 2022

Abstract
Background
Lateral ankle sprain (LAS) is a common injury. Conservative care is not uniformly effective. Chronic ankle instability (CAI) results in up to 70% of patients with LAS in the physically active population. LAS, together with subsequent osteochondral lesions and pain in many patients, leads to the development of post-traumatic osteoarthritis, resulting in a substantial direct and indirect personal and societal health burden. Dextrose prolotherapy (DPT) is an injection-based therapy for many chronic musculoskeletal conditions but has not been tested for CAI. This protocol describes a randomized controlled trial to test the efficacy of DPT versus normal saline (NS) injections for chronic ankle instability (CAI).

Methods and analysis
A single-center, parallel-group, randomized controlled trial will be conducted at a university-based primary care clinic in Hong Kong. A total of 114 patients with CAI will be randomly allocated (1:1) to DPT and NS groups. The primary outcome will be the Cumberland Ankle Instability Tool scores at 1 year. The secondary outcomes will be the number of re-sprains in 1 year, the Star Excursion Balance Test, the 5-level of EuroQol 5-dimension questionnaire, and the Foot and Ankle Ability Measure. All outcomes will be evaluated at baseline and at 16, 26, and 52 weeks using a linear mixed model.

Discussion
We hypothesized the DPT is a safe, easily accessible, and effective treatment for patients with CAI. This RCT study will inform whether DPT could be a primary non-surgical treatment for CAI.

Trial registration
Chinese Clinical Trial Registry ChiCTR2000040213. Registered on 25 November 2020.
A second-order dynamic and static ship path planning model based on reinforcement learning and heuristic search algorithms
Authors: Yuan Junfeng , Wan Jian , Zhang Xin , Xu Yang , Zeng Yan , Ren Yongjian 
Published: December 2022

AbstractShip path planning plays an important role in the intelligent decision-making system which can provide important navigation information for ship and coordinate with other ships via wireless networks. However, existing methods still suffer from slow path planning and low security problems. In this paper, we propose a second-order ship path planning model, which consists of two main steps, i.e., first-order static global path planning and second-order dynamic local path planning. Specifically, we first create a raster map using ArcGIS. Second, the global path planning is performed on the raster map based on the Dyna-Sarsa($$\lambda$$
λ
) model, which integrates the eligibility trace and the Dyna framework on the Sarsa algorithm. Particularly, the eligibility trace has a short-term memory for the trajectory, which can improve the convergence speed of the model. Meanwhile, the Dyna framework obtains simulation experience through simulation training, which can further improve the convergence speed of the model. Then, the improved ship trajectory prediction model based on stacked bidirectional gated recurrent unit is used to identify the risk of ship collision and switch the path planning from the first order to the second order. Finally, the second-order dynamic local path planning is presented based on the FCC-A* algorithm, where the cost function of the traditional path planning A* algorithm is rewritten using the fuzzy collision cost membership function (fuzzy collision cost, FCC) to reduce the collision risk of ships. The proposed model is evaluated on the Baltic Sea geographic information and ship trajectory datasets. The experimental results show that the eligibility trace and the Dyna learning framework in the proposed model can effectively improve the planning efficiency of the ship’s global path planning, and the collision risk membership function can effectively reduce the number of collisions in A* local path planning and thus improve the navigation safety of encountering ships.
Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis
Authors: Wang Yintang , Gao Tong , Meng Chang , Li Siyuan , Bi Lei , Geng Yu , Zhang Ping 
Published: December 2022

Abstract
Objectives
Heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) are associated with significant morbidity and mortality, as well as growing health and economic burden. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are very promising for the outcome improvement of patients with HFpEF or HFmrEF. The meta-analysis was performed to investigate the effects of SGLT2 inhibitors in HFpEF or HFmrEF, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify.

Methods
Studies were searched in electronic databases from inception to November, 2022. We performed a meta-analysis to estimate the effect of SGLT2 inhibitors on clinical endpoints in patients with HFpEF or HFmrEF, using trial-level data with consistent endpoint definitions. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Hazard ratio (HR) was pooled with 95% confidence interval (CI) for dichotomous data. This study was registered with INPLASY 2022110095.

Results
Six studies involving 15,989 participants were included into the final analysis. Pooled analyses revealed that SGLT2 inhibitors significantly reduced the composite of HF hospitalization or cardiovascular death [HR: 0.79 (0.72–0.85); I2 = 0%; P < 0.00001] and HF hospitalizations [HR: 0.74 (0.67–0.82); I2 = 0%; P < 0.00001]. This finding was seen in both HFmrEF trials [HR: 0.76 (0.67–0.87); I2 = 49%; P < 0.0001] and HFpEF subgroup studies [HR: 0.70 (0.53–0.93); I2 = 0%; P = 0.01]. The incidence of any serious adverse events [OR: 0.89 (0.83–0.96); I2 = 0%; P = 0.002] was significantly lower in the SGLT2 inhibitor arm. No significant differences were observed between the two groups with regard to cardiovascular death and all-cause death.

Conclusions
This meta-analysis of patients with heart failure of left ventricular ejection fraction (LVEF) > 40% showed that SGLT2 inhibitors significantly reduce the risk of the composite of cardiovascular death and hospitalization for heart failure, but not cardiovascular death and all-cause death. Nevertheless, given that SGLT2 inhibitors may reduce the risk of hospitalization for heart failure, they should be considered the fundamental treatment for all patients with HFpEF or HFmrEF.
A personal acquisition time regimen of 68Ga-DOTATATE total-body PET/CT in patients with neuroendocrine tumor (NET): a feasibility study
Authors: Xiao Jie , Yu Haojun , Sui Xiuli , Liu Guobing , Cao Yanyan , Yanzhao Zhao , Zhang Yiqiu , Hu Pengcheng , Cheng Dengfeng , Shi Hongcheng 
Published: December 2022

Abstract
Background
The injection activity of tracer, acquisition time, patient-specific photon attenuation, and large body mass, can influence on image quality. Fixed acquisition time and body mass related injection activity in clinical practice results in a large difference in image quality. Thus, this study proposes a patient-specific acquisition time regimen of 68 Ga-DOTATATE total-body positron emission tomography-computed tomography (PET/CT) to counteract the influence of body mass (BM, kg) on image quality, and acquire an acceptable and constant image of patients with neuroendocrine tumors (NETs).

Methods
The development cohort consisting of 19 consecutive patients with full activity (88.7–204.9 MBq, 2.0 ± 0.1 MBq/kg) was to establish the acquisition time regimen. The liver SNR (signal-to-noise ratio, SNRL) was normalized (SNRnorm) by the product of injected activity (MBq) and acquisition time (min). Fitting of SNRnorm against body mass (BM, kg) in linear correlation was performed. Subjective assessment of image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL, and an optimized acquisition regimen based on BM was proposed, and validated its feasibility through the validation cohort of 57 consecutive NET patients with half activity (66.9 ± 11.3 MBq, 1.0 ± 0.1 MBq/kg) and a fixed acquisition time regimen.

Results
The linear correlation (R2 = 0.63) between SNRnorm and BM (kg) was SNRnorm = -0.01*BM + 1.50. The threshold SNRL of acceptable image quality was 11.2. The patient-specific variable acquisition time regimen was determined as: t (min) = 125.4/(injective activity)*(-0.01*BM + 1.50)2. Based on that proposed regimen, the average acquisition time for acceptable image quality in the validation cohort was 2.99 ± 0.91 min, ranging from 2.18 to 6.35 min, which was reduced by 36.50% ~ 78.20% compared with the fixed acquisition time of 10 min. Subjective evaluation showed that acceptable image quality could be obtained at 3.00 min in the validation group, with an average subjective score of 3.44 ± 0.53 (kappa = 0.97, 95% CI: 0.96 ~ 0.98). Bland–Altman analysis revealed good agreement between the proposed regimen and the fixed acquisition time cohort.

Conclusion
A patient-specific acquisition time regimen was proposed in NET patients in development cohort and validated its feasibility in patients with NETs in validation cohort by 68 Ga-DOTATATE total-body PET/CT imaging. Based on the proposed regimen, the homogenous image quality with optimal acquisition time was available independent of body mass.
Induction of pancreatic neoplasia in the KRAS/TP53 Oncopig
Authors: Mondal Pinaki , Patel Neesha S. , Bailey Katie , Aravind Shruthishree , Cartwright Sara B. , Hollingsworth Michael A. , Lazenby Audrey J. , Carlson Mark A. 
Published: December 2022

ABSTRACT
The 5-year survival of pancreatic cancer (PC) remains low. Murine models may not adequately mimic human PC and can be too small for medical device development. A large-animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine containing KRASG12D and TP53R167H). The oncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) into one of the main pancreatic ducts. Resultant tumors were characterized by histology, cytokine expression, exome sequencing and transcriptome analysis. Ten of 14 Oncopigs (71%) had gross tumor within 3 weeks. At necropsy, all of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Oncopigs with injections without Cre recombinase and wild-type pigs with AdCre injection did not show notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity to the molecular signatures and pathways of human PC. Although further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC.
This article has an associated First Person interview with the joint first authors of the paper.
Present situation of bacterial neuroinfections across the globe – review
Authors: Bielewicz Krzysztof , Ryba Karolina , Karaś Anna , Kawałko Kinga , Pondel Kamil 
Published: December 2022

Bacterial meningitis is still life-treating disease, which cause about 1.2 million cases and it is responsible for over 100 thousand of deaths across the globe. [2][ The most common pathogens which case the disease are Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae and Listeria monocytogenes. Morbidity is significantly higher in Africa, than in other regions in the world. Region of the highest frequency of new cases is located in sub-Saharan Africa and called meningitis belt. Vaccination campaigns against bacterial, mostly meningococcal were conducted in some of these regions and the benefits of it were seen [5].
Young children and elderly patients are predisposed to have bacterial meningitis. In pediatric population the disease usually presents as fever, seizures, vomiting, chills, altered mental status and stiff neck. [4] Development of each country have impact on mortality and morbidity among children. [6] Elderly patients, because of their comorbidity are also predisposed to bacterial meningitis. Diseases like diabetes mellitus, alcoholism, cancer, HIV/AIDS or being after splenectomy may make the patients susceptible for bacterial invasion of CNS.
Also, every factor which interrupt blood-brain barrier, like trauma or surgery may cause the infection.
Intracerebral hemorrhage can be consequence of the infection, which cause other complications like impaired consciousness, focal neurological deficit, need of mechanical ventilation and seizures. It was noticed that in most of cases bacterial meningitis had S.pneumoniae etiology.
Analysis of the mature milk composition of women giving birth prematurely and on time
Authors: Dombrowska-Pali Agnieszka , Gebuza Grażyna , Kaźmierczak Marzena 
Published: December 2022

Introduction: The composition of breast milk is not consistent; its variability is determined by the nutritional needs of the baby: duration of pregnancy, phases of a single feeding, lactation period, variability of fat concentration.
The aim: To assess the energy and essential nutrients content in mature milk from mothers delivering preterm and full-term infants.
Material and methods: 75 women participated in the study, at 4 weeks postpartum. The study sample was divided into three groups according to the duration of pregnancy: G1>=32 weeks of pregnancy, G2) 33-36 weeks of pregnancy, G3) <=37 weeks of pregnancy. The analysis of breast milk composition was performed with the Miris Human Milk Analysis analyser.
Results: The pregnancy duration of a sample of women participating in the study does not differentiate the nutritional composition and energy content in breast milk (p>0.05) analysed in the fourth week of lactation.
Conclusions: The assessment of the milk from women who gave birth on time and prematurely showed no significant differences in protein, fats, carbohydrates and energy content considering the same stage of lactation. However, it should be emphasised that not only is human milk considered to be a nutrient but also functional food. Due to the content of enzymes, hormones and growth factors, breast milk has a protective function. It is a part of treatment for premature babies. Nevertheless, the results of our study indicate the need for further research measuring the macronutrients of human milk in order to individualize more the nutritional approach for a particularly demanding group of newborns, which may help optimize their growth and development.
endocrine background of meningioma carcinogenesis
Authors: Gałązka Jakub Krzysztof , Homa Piotr , Domagalski Łukasz 
Published: December 2022

Meningiomas, being mostly benign tumors, are derived from the arachnoid cap cells, their etiopathogenesis is based on various factors. The etiology of sporadic meningiomas is not yet known. Many factors have been identified as possible causes of the development of intracranial meningiomas. These include head trauma, viral infections, deletion in the NF2 gene, the use of cell phones, and sex hormones. The review is based on a endocrine factors, playing a role in meningioma carcinogenesis.
The carcinogenesis of meningioma appeals to be profoundly dependent from hormonal factors. Mayor ones, usually underlined in according to their prognostic significance, are female sex hormones. Due to this, meningiomas are twice as more likely to occur in female than in male patients. The other group of hormones appointed to play a role in meningioma carcinogenesis are adipokines in general – and leptin in particular. Leptin secretion correlates with BMI elevation, what may explain the confirmed linking between obesity and brain tumors. The scientific literature has documented the occurrence of meningioma in five patients with CAH, but the role of cortical axis and/or ACTH secretion impairments is still under consideration. Authors didn’t find any publication about the role of thyroid disorders in meningioma carcinogenesis.
The carcinogenesis of meningioma appeals to be profoundly dependent from hormonal factors. The effects of female sex hormones and adipokines are under a significant consideration, and may be useful in severity prediction. Basic science research should be focused on ACTH secretion in meningioma and possible common genetic etiopathogenesis of meningioma and CAH.
A Mocca Pode Inovar?
Authors: Beuter Junior Nelson , Faccin Kadígia , Fassina Santini Mateus Augusto , Kremer Sott Michele 
Published: December 2022

Este caso é uma narrativa com enredo fictício baseado em fatos reais vivenciados pelos autores ao longo das suas trajetórias profissionais. Para tanto, apresenta-se a Mocca, uma empresa familiar do ramo calçadista com 34 anos de existência e que viveu seu ápice no final dos anos 90. Entretanto, no início dos anos 2000 viu suas vendas diminuírem por conta da redução de barreiras comerciais e da migração do setor calçadista para os grandes centros do país – desde então a empresa passa por uma estagnação. Agora a Mocca precisa se reinventar e inovar para voltar a crescer. Algumas questões são levantadas e os gestores da Mocca precisam identificar ferramentas de inovação que auxiliem a implementação de estratégias de inovação para o crescimento do negócio. Assim, a Mocca busca alternativas para implementar inovações que a recoloquem em um patamar competitivo. Neste caso, com o apoio de ferramentas de gestão da inovação, os alunos são orientados a discutirem e explorarem soluções para a Mocca.