bluuebunny/crossref_metadata_2025 huggingface dataset:
Current state of ethical challenges reported in Saudi Arabia: a systematic review & bibliometric analysis from 2010 to 2021
Authors: Woodman Alexander , Waheed Khawaja Bilal , Rasheed Mohammad , Ahmad Shakil
Published: August 2022

Background

Over the past few years, five domains of importance about the current state of bioethics in Saudi Arabia have shaped the perspective of most research: doctor-patient relationship, informed consent, do-not-resuscitate, organ donation, and transplantation, medical students’ knowledge and attitudes about medical ethics curriculum. This systematic review aimed to systematically identify, compile, describe and discuss ethical arguments and concepts in the best-studied domains of bioethics in Saudi Arabia and to present cultural, social, educational, and humane perspectives.

Methods

Six databases were searched using Boolean operators (PubMed, Embase, Web of Science, Scopus, CINAHL, Google Scholar) from December 2020–June 2021. The search and report process followed the statement and flowchart of preferred reporting items for systematic reviews and meta-analyses (PRISMA).

Resutls

The search resulted in 1651 articles, of which 82 studies were selected for a final review and assessment. There is a gradual increase in research, whereby a substantial increase was observed from 2017. Most of the published articles focused on ‘Organ Donation & Transplantation’ with 33 articles, followed by ‘Doctor-Patient Relations’ with 18 publications. Most of the published articles were from Central Province (33), followed by Western Province (16). The authorship pattern showed a collaborative approach among researchers. The thematic analysis of keywords analysis showed that ‘Saudi Arabia,’ ‘attitude PHC,’ ‘organ donation,’ ‘knowledge and education,’ and ‘donation’ have been used the most commonly.

Conclusion

This systematic quantitative synthesis is expected to guide researchers, stakeholders, and policymakers about the strengths and gaps in knowledge and attitudes regarding medical ethics in Saudi Arabia, both among the general public and health professionals.
Detection of developmental dysplasia of the hip in X-ray images using deep transfer learning
Authors: Fraiwan Mohammad , Al-Kofahi Noran , Ibnian Ali , Hanatleh Omar
Published: August 2022

Background

Developmental dysplasia of the hip (DDH) is a relatively common disorder in newborns, with a reported prevalence of 1–5 per 1000 births. It can lead to developmental abnormalities in terms of mechanical difficulties and a displacement of the joint (i.e., subluxation or dysplasia). An early diagnosis in the first few months from birth can drastically improve healing, render surgical intervention unnecessary and reduce bracing time. A pelvic X-ray inspection represents the gold standard for DDH diagnosis. Recent advances in deep learning artificial intelligence have enabled the use of many image-based medical decision-making applications. The present study employs deep transfer learning in detecting DDH in pelvic X-ray images without the need for explicit measurements.

Methods

Pelvic anteroposterior X-ray images from 354 subjects (120 DDH and 234 normal) were collected locally at two hospitals in northern Jordan. A system that accepts these images as input and classifies them as DDH or normal was developed using thirteen deep transfer learning models. Various performance metrics were evaluated in addition to the overfitting/underfitting behavior and the training times.

Results

The highest mean DDH detection accuracy was 96.3% achieved using the DarkNet53 model, although other models achieved comparable results. A common theme across all the models was the extremely high sensitivity (i.e., recall) value at the expense of specificity. The F1 score, precision, recall and specificity for DarkNet53 were 95%, 90.6%, 100% and 94.3%, respectively.

Conclusions

Our automated method appears to be a highly accurate DDH screening and diagnosis method. Moreover, the performance evaluation shows that it is possible to further improve the system by expanding the dataset to include more X-ray images.
Development and preliminary validation of a public health emergency competency model for medical staffs of national health emergency teams in China
Authors: Zhao Yuhan , Wang Yuanyuan , Zhang Ting , Wang Miaomiao , Ye Xiaojun , Wang Xintian , Sun Hongwei
Published: August 2022

Background

In the present study, we attempted to develop and validate a participatory competency model for medical workers and then evaluate the current status of competency characteristics of Chinese medical workers.

Methods

The competency model was constructed in a multistage process, including literature review, expert consultation, critical incident and focus group interview. A pilot study was conducted to refine the initial model among 90 participators and the viability and reliability were evaluated by a questionnaire survey among 121 medical workers. Then, the current status of competency characteristics was measured based on the final version of competency model.

Results

In the pilot study, ten questionnaires were dropped for the poor quality and thus the eligible rate was 92% (138/150). KMO value was 0.785 and Bartlett test showed that the χ2 = 6464.546 (df = 903) and p value < 0.001. Then, 10 items with double loading and factor loading < 0.4 were deleted. Finally, 33 items were retained with the lowest factor loading value of 0.465. The validity and reliability of competency model were determined with Cronbach’s α coefficient of 0.975 and ICC value of 0.933. Finally, a revised competency model with 5 dimensions and 31 items was obtained. The overall competencies of current medical workers were in a high level, except for emergency knowledge related competencies. Age was an independent factor affecting the competencies.

Conclusions

Our competency model was a reliable and validated tool for assessing the competences of medical staffs against public health emergencies, and the overall competencies of current medical workers in China were in a high level, except for emergency knowledge related competencies.
Barriers to accessing health care for people with chronic conditions: a qualitative interview study
Authors: Schwarz Tanja , Schmidt Andrea E. , Bobek Julia , Ladurner Joy
Published: August 2022

Background

There is a growing interest in redesigning healthcare systems to increase access to and coordination across care settings for people with chronic conditions. We aim to gain a better understanding of the barriers faced by (1) children with chronic bronchial asthma, (2) adults with non-specific chronic back pain, and (3) older people with pre-existing mental illness/es in Austria’s fragmented social health insurance system.

Methods

Using a qualitative design, we conducted semi-structured interviews face-to-face and by telephone with health service providers, researchers, experts by experience (persons with lived/ personal experience, i.e., service users, patient advocates or family members/carers), and employees in public health administration between July and October 2019. The analysis and interpretation of data were guided by Levesque’s model of access, a conceptual framework used to evaluate access broadly according to different dimensions of accessibility to care: approachability, acceptability, availability and accommodation, affordability, and appropriateness.

Results

The findings from the 25 expert interviews were organised within Levesque’s conceptual framework. They highlight a lack of coordination and defined patient pathways, particularly at the onset of the condition, when seeking a diagnosis, and throughout the care process. On the supply side, patterns of poor patient-provider communication, lack of a holistic therapeutic approach, an urban-rural divide, strict separation between social care and the healthcare system and limited consultation time were among the barriers identified. On the demand side, patients’ ability to perceive a need and to subsequently seek and reach healthcare services was an important barrier, closely linked to a patient’s socio-economic status, health literacy and ability to pay.

Conclusions

While studies on unmet needs suggest a very low level of barriers to accessing health care in the Austrian context, our study highlights potential ‘invisible’ barriers. Barriers to healthcare access are of concern for patients with chronic conditions, underlining existing findings about the need to improve health services according to patients’ specific needs. Research on how to structure timely and integrated care independent of social and economic resources, continuity of care, and significant improvements in patient-centred communication and coordination of care would be paramount.
Screening for type 2 diabetes and periodontitis patients (CODAPT-My©): a multidisciplinary care approach
Authors: Abdul Aziz Aznida Firzah , Mohd-Dom Tuti Ningseh , Mustafa Norlaila , Said Abdul Hadi , Ayob Rasidah , Mohamed Isa Salbiah , Hatah Ernieda , Wan Puteh Sharifa Ezat , Mohd Alwi Mohd Farez Fitri
Published: August 2022

Background

The practice of referring diabetic patients for dental intervention has been poor despite awareness and knowledge of the oral health effects of diabetes. Likewise, dentists treating patients receiving diabetes treatment are rarely updated on the glycaemic status and as a result, the opportunity for shared management of these patients is missed. This study aimed to provide a standardised care pathway which will initiate screening for diabetes from dental clinics and link patients with primary care for them to receive optimised care for glycaemic control.

Method

A Modified Delphi technique was employed to obtain consensus on recommendations, based on current evidence and best care practices to screen for diabetes among patients attending dental clinics for periodontitis. Expert panel members were recruited using snowball technique where the experts comprised Family Medicine Specialists (5), Periodontists (6), Endocrinologists (3) and Clinical Pharmacists (4) who are involved in management of patients with diabetes at public and private healthcare facilities. Care algorithms were designed based on existing public healthcare services.

Results

The CODAPT©panel recommends referral to primary care for further evaluation of glycaemic status if patients diagnosed with periodontitis record fasting capillary blood glucose levels ≥ 5.6 mmol/L. Intervention treatment options for prediabetes are listed, and emphasis on feedback to the dental healthcare team is outlined specifically.

Conclusion

The CODAPT©care pathway has the potential to link dental clinics with primary care for diagnosis and/or optimised treatment of prediabetes/diabetes among patients receiving periodontitis treatment.
NHLRC2 expression is increased in idiopathic pulmonary fibrosis
Authors: Kreus Mervi , Lehtonen Siri , Hinttala Reetta , Salonen Johanna , Porvari Katja , Kaarteenaho Riitta
Published: August 2022

Background

Variants of NHL repeat-containing protein 2 (NHLRC2) have been associated with severe fibrotic interstitial lung disease in early childhood and NHLRC2 has been listed as a differentially expressed gene between rapidly and slowly progressing idiopathic pulmonary fibrosis (IPF) patients. However, its cell type-specific localization in human lung tissue is unknown. The aim of this study was to evaluate NHLRC2 mRNA and protein expression in different cell types of lung tissue samples and to investigate the effect of transforming growth factor (TGF)-β1 exposure on NHLRC2 expression in vitro.

Methods

The NHLRC2 expression in lung tissue samples was studied by immunohistochemistry (50 IPF, 10 controls) and mRNA in situ hybridization (8 IPF, 3 controls). The immunohistochemical NHLRC2 expression was quantified with image analysis software and associated with the clinical and smoking data of the patients. NHLRC2 expression levels in primary stromal and small airway epithelial cell lines after exposure to TGF-β1 was measured by quantitative reverse transcription polymerase chain reaction and Western blot analysis.

Results

NHLRC2 expression was detected especially in bronchiolar epithelial cells, type II pneumocytes and macrophages in normal lung. In the lungs of IPF patients, NHLRC2 was mainly expressed in hyperplastic alveolar epithelial cells lining fibroblast foci and honeycombs. NHLRC2 expression assessed by image analysis was higher in IPF compared to controls (p < 0.001). Ever-smokers had more prominent NHLRC2 staining than non-smokers (p = 0.037) among IPF patients. TGF-β1 exposure did not influence NHLRC2 levels in lung cell lines.

Conclusions

NHLRC2 expression was higher in IPF compared to controls being widely expressed in type II pneumocytes, macrophages, bronchiolar epithelium, and hyperplastic alveolar epithelium. Additionally, its expression was not regulated by the exposure to TGF-β1 in vitro. Further studies are needed to clarify the role of NHLRC2 in IPF.
Contemporary use of SGLT2 inhibitors in heart failure patients with diabetes mellitus: a comparison of DPP4 inhibitors in a nationwide electric health database of the superaged society
Authors: Nakai Michikazu , Iwanaga Yoshitaka , Kanaoka Koshiro , Sumita Yoko , Nishioka Yuichi , Myojin Tomoya , Kubo Shinichiro , Okada Katsuki , Soeda Tsunenari , Noda Tatsuya , Sakata Yasushi , Imamura Tomoaki , Saito Yoshihiko , Yasuda Satoshi , Miyamoto Yoshihiro
Published: August 2022

Background

There is a lack of recent data reflecting the actual use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for heart failure (HF) and type 2 diabetes (DM) in the superaged society. The present study investigated the association between the use of SGLT2 inhibitors and one-year prognosis in patients hospitalized across a broad spectrum of HF patients with DM in the superaged society using the Nationwide Electric Health Database in Japan.

Methods

The patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2019. A cohort of 2,277 users of SGLT2 inhibitors and 41,410 users of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors were compared. A propensity score-matched cohort study of 2,101 users of each inhibitor was also conducted. A multivariable multilevel mixed-effects survival model was conducted with adjustments, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results

Among 300,398 patients discharged with HF in 4,176 hospitals, 216,016 (71.9%) were 75 years or older, and 60,999 (20.3%) took antidiabetic medications. Among them, the patients treated with SGLT2 inhibitors were younger and had a more severe status than those treated with DPP4 inhibitors. Kaplan–Meier analysis showed that patients treated with SGLT2 inhibitors had a lower mortality risk and HF readmission. In propensity-matched cohorts, SGLT2 inhibitor use was associated with a lower risk of mortality and HF readmission than DPP-4 inhibitor use (HR [95% CI]; 0.70 [0.56, 0.89] and 0.52 [0.45, 0.61], respectively). Very elderly (≥ 75 years) patients showed similar results. Favorable effects were also observed across all age groups, including ≥ 75 years, in patients with coronary artery disease or atrial fibrillation and with concomitant β-blocker, diuretics, or insulin.

Conclusion

The use of SGLT2 inhibitors at discharge was associated with a lower risk of one-year mortality and HF readmission in patients across a broad spectrum of HF with DM in the superaged society. The findings further support the benefits of using SGLT2 inhibitors in very elderly HF care and complement the current evidence.
Fabrication of multifunctional metal–organic frameworks nanoparticles via layer-by-layer self-assembly to efficiently discover PSD95-nNOS uncouplers for stroke treatment
Authors: Ding Yingying , Jin Yang , Peng Tao , Gao Yankun , Zang Yang , He Hongliang , Li Fei , Zhang Yu , Zhang Hongjuan , Chen Lina
Published: August 2022

Background

Disruption of the postsynaptic density protein-95 (PSD95)—neuronal nitric oxide synthase (nNOS) coupling is an effective way to treat ischemic stroke, however, it still faces some challenges, especially lack of satisfactory PSD95-nNOS uncouplers and the efficient high throughput screening model to discover them.

Results

Herein, the multifunctional metal–organic framework (MMOF) nanoparticles as a new screening system were innovatively fabricated via layer-by-layer self-assembly in which His-tagged nNOS was selectively immobilized on the surface of magnetic MOF, and then PSD95 with green fluorescent protein (GFP-PSD95) was specifically bound on it. It was found that MMOF nanoparticles not only exhibited the superior performances including the high loading efficiency, reusability, and anti-interference ability, but also possessed the good fluorescent sensitivity to detect the coupled GFP-PSD95. After MMOF nanoparticles interacted with the uncouplers, they would be rapidly separated from uncoupled GFP-PSD95 by magnet, and the fluorescent intensities could be determined to assay the uncoupling efficiency at high throughput level.

Conclusions

In conclusion, MMOF nanoparticles were successfully fabricated and applied to screen the natural actives as potential PSD95-nNOS uncouplers. Taken together, our newly developed method provided a new material as a platform for efficiently discovering PSD95-nNOS uncouplers for stoke treatment.

Graphical Abstract
Three-dimensional culture models of human endometrium for studying trophoblast-endometrium interaction during implantation
Authors: Li Xintong , Kodithuwakku Suranga P. , Chan Rachel W. S. , Yeung William S. B. , Yao Yuanqing , Ng Ernest H. Y. , Chiu Philip C. N. , Lee Cheuk-Lun
Published: August 2022

During implantation, a symphony of interaction between the trophoblast originated from the trophectoderm of the implanting blastocyst and the endometrium leads to a successful pregnancy. Defective interaction between the trophoblast and endometrium often results in implantation failure, pregnancy loss, and a number of pregnancy complications. Owing to ethical concerns of using in vivo approaches to study human embryo implantation, various in vitro culture models of endometrium were established in the past decade ranging from two-dimensional cell-based to three-dimensional extracellular matrix (ECM)/tissue-based culture systems. Advanced organoid systems have also been established for recapitulation of different cellular components of the maternal–fetal interface, including the endometrial glandular organoids, trophoblast organoids and blastoids. However, there is no single ideal model to study the whole implantation process leaving more research to be done pursuing the establishment of a comprehensive in vitro model that can recapitulate the biology of trophoblast-endometrium interaction during early pregnancy. This would allow us to have better understanding of the physiological and pathological process of trophoblast-endometrium interaction during implantation.
Tracking of menstrual cycles and prediction of the fertile window via measurements of basal body temperature and heart rate as well as machine-learning algorithms
Authors: Yu Jia-Le , Su Yun-Fei , Zhang Chen , Jin Li , Lin Xian-Hua , Chen Lu-Ting , Huang He-Feng , Wu Yan-Ting
Published: August 2022

Background

Fertility awareness and menses prediction are important for improving fecundability and health management. Previous studies have used physiological parameters, such as basal body temperature (BBT) and heart rate (HR), to predict the fertile window and menses. However, their accuracy is far from satisfactory. Additionally, few researchers have examined irregular menstruators. Thus, we aimed to develop fertile window and menstruation prediction algorithms for both regular and irregular menstruators.

Methods

This was a prospective observational cohort study conducted at the International Peace Maternity and Child Health Hospital in Shanghai, China. Participants were recruited from August 2020 to November 2020 and followed up for at least four menstrual cycles. Participants used an ear thermometer to assess BBT and wore the Huawei Band 5 to record HR. Ovarian ultrasound and serum hormone levels were used to determine the ovulation day. Menstruation was self-reported by women. We used linear mixed models to assess changes in physiological parameters and developed probability function estimation models to predict the fertile window and menses with machine learning.

Results

We included data from 305 and 77 qualified cycles with confirmed ovulations from 89 regular menstruators and 25 irregular menstruators, respectively. For regular menstruators, BBT and HR were significantly higher during fertile phase than follicular phase and peaked in the luteal phase (all P < 0.001). The physiological parameters of irregular menstruators followed a similar trend. Based on BBT and HR, we developed algorithms that predicted the fertile window with an accuracy of 87.46%, sensitivity of 69.30%, specificity of 92.00%, and AUC of 0.8993 and menses with an accuracy of 89.60%, sensitivity of 70.70%, and specificity of 94.30%, and AUC of 0.7849 among regular menstruators. For irregular menstruators, the accuracy, sensitivity, specificity and AUC were 72.51%, 21.00%, 82.90%, and 0.5808 respectively, for fertile window prediction and 75.90%, 36.30%, 84.40%, and 0.6759 for menses prediction.

Conclusions

By combining BBT and HR recorded by the Huawei Band 5, our algorithms achieved relatively ideal performance for predicting the fertile window and menses among regular menstruators. For irregular menstruators, the algorithms showed potential feasibility but still need further investigation.

Trial registration

ChiCTR2000036556. Registered 24 August 2020.
Clinical efficacy and safety of posterior minimally invasive surgery in cervical spondylosis: a systematic review
Authors: Lv Junqiao , Mei Jun , Feng Xiaoning , Tian Xuefeng , Sun Lin
Published: August 2022

Background

Posterior minimally invasive surgery has been increasingly used in in recent years for the clinical treatment of cervical spondylosis. However, this treatment remains challenging and has not been comprehensively reported. The aim of this study was to provide a systematic review of posterior minimally invasive treatment for cervical spondylosis to demonstrate the clinical efficacy and safety of this procedure.

Method

We collected information from patients with myelopathy or radiculopathy cervical spondylosis who underwent posterior minimally invasive surgery and verified the clinical efficacy and safety of these surgeries with different measurement indicators from five electronic databases: the Nurick, visual analog scale score, Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), EuroQol Five Dimensions Questionnaire (EQ-5D) score, Short-Form Health Survey Physical Component Summary (SF12-PCS) questionnaire score, Short-Form Health Survey Mental Component Summary (SF12-MCS) questionnaire score, and the MOS item short form health survey (HF-36) score. The decompression effect, cervical spine stability, average surgery time, surgical blood loss volume, length of hospital stay, and related complications were included in the descriptive analysis. Reporting of this protocol followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines checklist.

Results

We identified 14 observational studies of cervical spondylosis with 479 patients, mainly including 197 cases of myelopathy and 207 cases of radiculopathy. Channel and endoscopic techniques were used. This study was certified by PROSPERO: CRD42021290074. Significant improvements in the quantitative indicators (Neck-VAS in 9 studies, JOA in 7 studies, NDIs in 5 studies, Nurick, ARM-VAS, and EQ-5D in 2 studies each, and the SF12-PCS, SF12-MCS, and HF-36 in 1 study each) were observed between pre- and postoperation (P < 0.05), and satisfactory clinical significance was acquired in the descriptive indicators [average surgery time (94.56 ± 37.26 min), blood loss volume (68.78 ± 103.31 ml), average length of stay (2.39 ± 1.20 d), and cervical spine stability after surgery]. Additionally, we showed that there was a 4.9% postoperative complication rate and the types of complications that may occur.

Conclusion

Posterior minimally invasive surgery is an effective and safe method for the treatment of cervical spondylosis and is a recommended optional surgical procedure for single-segment myelopathy and radiculopathy.
Anatomic, computed tomographic, and ultrasonographic assessment of the lymph nodes in presumed healthy adult cats: the abdomen, pelvis, and hindlimb
Authors: Tobón Restrepo Mauricio , Novellas Rosa , Aguilar Adrià , Moll Xavier , Espada Yvonne
Published: August 2022

Background

The computed tomography (CT) and ultrasonography (US) features of lymph nodes of the abdomen, pelvis, and hindlimb in healthy cats are poorly described in the current literature. A prospective anatomic and reference interval study was therefore performed. The lymph nodes of six feline cadavers were identified, and dimensions were measured (length, width, and height). The lymph nodes from 30 healthy adult cats were identified and measured using CT (pre- and postcontrast) and US. The identification and dimensions of the separate lymph nodes were compared between imaging techniques and the anatomic study.

Results

The identification of lymph nodes was most frequent in CT, and the dimensions were overall larger than those identified and measured in US and the anatomic study. The caudal epigastric and sacral lymph nodes were not identified in the anatomic study. The ischiatic, lumbar aortic, internal iliac, and caudal epigastric lymph nodes were not visualized in US. The height presented the main statistical differences among techniques. The lymph nodes were mainly homogeneous in pre- and postcontrast CT and US images. Some lymph nodes showed a hyperattenuating periphery with a hypoattenuating center (on pre- and postcontrast images) and a hypo-/isoechoic periphery with a hyperechoic center, representing the hilar fat. The lymph nodes were commonly elongated and rounded except for the jejunal lymph nodes, which had an irregular shape.

Conclusions

The assessment of most of the abdominal, pelvic, and hindlimb lymph nodes in the cat is feasible using CT and US, with CT performing best. Factors like the amount of adipose tissue and contrast administration subjectively improved the lymph node visualization and assessment. The measurements and features reported are proposed as reference values.
WISP1 induces ovarian cancer via the IGF1/αvβ3/Wnt axis
Authors: Li Yan , Wang Fangfang , Liu Tianyi , Lv Nan , Yuan Xiaolei , Li Peiling
Published: August 2022

Background

This study intended to clarify the mechanisms by which WISP1-mediated IGF1/αvβ3/Wnt axis might affect the progression of ovarian cancer.

Methods

Bioinformatics analysis was implemented for pinpointing expression of IGF1 and WISP1 which was verified through expression determination in clinical tissue samples and cells. Next, gain- or loss-of-function experimentations were implemented for testing CAOV4 and SKOV3 cell biological processes. The interaction between WISP1 and IGF1 was verified by co-immunoprecipitation and the molecular mechanism was analyzed. Finally, ovarian cancer nude mouse models were prepared to unveil the in vivo effects of WISP1/IGF1.

Results

IGF1 and WISP1 expression was elevated in ovarian cancer tissues and cells, which shared correlation with poor prognosis of ovarian cancer sufferers. Elevated IGF1 induced malignant properties of ovarian cancer cells through activation of PI3K-Akt and Wnt signaling pathway. WISP1 was positively correlated with IGF1. WISP1 could enhance the interaction between IGF1 and αvβ3 to induce epithelial-mesenchymal transition. In vivo experiments also confirmed that upregulated WISP1/IGF1 induced tumorigenesis and metastasis of ovarian cancer cells.

Conclusion

In conclusion, WISP1 can facilitate ovarian cancer by activating Wnt via the interaction between IGF1 and αvβ3.
Targeting purine metabolism in ovarian cancer
Authors: Liu Jingchun , Hong Shasha , Yang Jiang , Zhang Xiaoyi , Wang Ying , Wang Haoyu , Peng Jiaxin , Hong Li
Published: August 2022

Purine, an abundant substrate in organisms, is a critical raw material for cell proliferation and an important factor for immune regulation. The purine de novo pathway and salvage pathway are tightly regulated by multiple enzymes, and dysfunction in these enzymes leads to excessive cell proliferation and immune imbalance that result in tumor progression. Maintaining the homeostasis of purine pools is an effective way to control cell growth and tumor evolution, and exploiting purine metabolism to suppress tumors suggests interesting directions for future research. In this review, we describe the process of purine metabolism and summarize the role and potential therapeutic effects of the major purine-metabolizing enzymes in ovarian cancer, including CD39, CD73, adenosine deaminase, adenylate kinase, hypoxanthine guanine phosphoribosyltransferase, inosine monophosphate dehydrogenase, purine nucleoside phosphorylase, dihydrofolate reductase and 5,10-methylenetetrahydrofolate reductase. Purinergic signaling is also described. We then provide an overview of the application of purine antimetabolites, comprising 6-thioguanine, 6-mercaptopurine, methotrexate, fludarabine and clopidogrel. Finally, we discuss the current challenges and future opportunities for targeting purine metabolism in the treatment-relevant cellular mechanisms of ovarian cancer.

Graphical Abstract
The effects of the covid-19 pandemic on puberty: a cross-sectional, multicenter study from Turkey
Authors: Yesiltepe Mutlu Gul , Eviz Elif , Haliloglu Belma , Kirmizibekmez Heves , Dursun Fatma , Ozalkak Servan , Cayir Atilla , Sacli Beste Yuksel , Ozbek Mehmet Nuri , Demirbilek Huseyin , Hatun Sukru
Published: August 2022

Backgrounds

During the Coronavirus-19 disease (Covid-19) pandemic it was observed that the number of girls presenting with early puberty had increased. The aim of this study was to carry out a retrospective evaluation of the characteristics of girls who had been referred for evaluation of precocious puberty in five different pediatric endocrinology units, before and during the pandemic.

Methods

The study participants comprised 359 girls who were assigned into 2 groups a pre-pandemic group (n:214) and a pandemic group (n:145). Those participants (n:99) who had medical records in the follow-up period were classified into 3 subgroups according to the time of presentation and follow-up visits (group-1: first admission and follow-up visit before the pandemic, group-2: first admission before the pandemic, the follow-up visit during the pandemic, group-3: first admission and follow-up visit during the pandemic).

Results

The age at presentation and age at pubertal onset were both significantly lower in the pandemic group than those in the pre-pandemic group(8.1 vs 8.6, p: < 0.001,7.7 vs 7.9,p:0.013, respectively). There was no significant difference between the body mass index standard deviation scores (BMI-SDS) values of the groups (0.57 vs 0.51, p:0.430). The initiation rate of pubertal suppression therapy at the time of presentation was significantly higher in the pandemic group compared to that of the pre-pandemic group (7.7%vs 27.5%), and in groups-2 & 3 compared to group-1, during follow-up (20%&44%vs 8%).

Conclusion

Our research showed that the onset of puberty occurred earlier in the pandemic period compared to the previous year, and the need for pubertal suppression therapy increased during the pandemic.
Bedside assessment of left atrial pressure in critical care: a multifaceted gem
Authors: Bowcock Emma Maria , Mclean Anthony
Published: August 2022

Evaluating left atrial pressure (LAP) solely from the left ventricular preload perspective is a restrained approach. Accurate assessment of LAP is particularly relevant when pulmonary congestion and/or right heart dysfunction are present since it is the pressure most closely related to pulmonary venous pressure and thus pulmonary haemodynamic load. Amalgamation of LAP measurement into assessment of the ‘transpulmonary circuit’ may have a particular role in differentiating cardiac failure phenotypes in critical care. Most of the literature in this area involves cardiology patients, and gaps of knowledge in application to the bedside of the critically ill patient remain significant. Explored in this review is an overview of left atrial physiology, invasive and non-invasive methods of LAP measurement and their potential clinical application.

Graphical abstract
Effectiveness of repetitive transcranial magnetic stimulation against poststroke urinary incontinence: a study protocol for a randomized controlled trial
Authors: Jiang Wei , Tang Wen , Song Yunling , Feng Yali , Zhou Yuesan , Li Lang , Tan Botao
Published: August 2022

Background and purpose

Poststroke urinary incontinence (PSI) is prevalent in stroke survivors, and high-quality evidence is required to guide clinical practice. Previous studies have demonstrated the curative effect of repetitive transcranial magnetic stimulation (rTMS) for urinary incontinence in individuals with multiple sclerosis (MS), Parkinson’s disease (PD), and spinal cord injury (SCI). Here, we describe the protocol for a randomized controlled trial to evaluate the efficacy and safety of low-frequency rTMS on the contralesional primary motor cortex (M1) for the treatment of PSI.

Methods and analysis

In this single-centre randomized controlled trial for poststroke urinary incontinence, a total of 140 eligible patients will be randomly allocated into two groups. The rTMS group (n = 70) will receive low-frequency rTMS at the M1 along with routine medical care, while the control group will receive sham rTMS along with routine medical care. All participants will undergo 20 treatment sessions, five times a week for 4 weeks. The primary outcome measures will be the changes in the urodynamic test at baseline versus 4 weeks after intervention. The secondary outcomes include the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF), Overactive Bladder Symptom Score (OABSS), and pelvic floor muscle function.

Ethics and dissemination

The Institutional Review Board and Hospital Research Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University approved this trial, and the approval number is No. 2020-153. All methods will be carried out in accordance with the principles of the Declaration of Helsinki and relevant ethical guidelines covering informed consent, confidentiality, and data storage. After the study had been thoroughly described to the participants by a physician, all participants will provide written informed consent indicating their willingness to participate. The results will be disseminated to most of the population, including participants, researchers, healthcare providers, and sponsors.

Trial registration

URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100042688. Date of Registration: 2021-01-26.
A novel GnRH antagonist protocol based on LH levels versus traditional flexible GnRH antagonist protocol in PCOS patients undergoing in vitro fertilization: study protocol for a randomized controlled, non-inferiority trial
Authors: Liu Shan , Lv Ya-su , Han Shuo , Liu Minghui , Ma Shuai , Ren Haiying , Li Yuan
Published: August 2022

Background

The gonadotropin-releasing hormone (GnRH) antagonist protocol is advantageous given that it can avoid severe ovarian hyperstimulation syndrome (OHSS), especially for patients with polycystic ovary syndrome (PCOS). Basic and clinical evidence has shown that a threshold of luteinizing hormone (LH) stimulation is required for adequate follicular development and oocyte maturation. Ultra-low or high levels of LH are detrimental to pregnancy outcomes. We previously demonstrated that LH could be an indicator for the timing and dosage of antagonist administration in a retrospective study.

Methods/design

In this randomized, single-center, non-inferiority trial, we aim to test the hypothesis that there is no significant difference in cumulative ongoing pregnancy rates between PCOS patients stimulated with LH-based flexible protocol versus traditional flexible GnRH antagonist protocol. The primary efficacy endpoint will be the cumulative ongoing pregnancy rate per cycle. The secondary outcomes will be clinical pregnancy rate, cancelation rate, serious OHSS rate, and cost-efficiency. The cumulative ongoing pregnancy rate per cycle in PCOS women was 80%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 16% (two-sided: α, 2.5%; β, 20%) and a total of 196 patients were needed. Anticipating a 10% dropout rate, the total number of patients required was 216.

Discussion

The results of this study will provide evidence for the efficacy and safety of the LH-based flexible GnRH antagonist protocol in PCOS patients. Moreover, it evaluates the cost-efficiency of both protocols.

Trial registration

Chinese Clinical Trial Registry ChiCTR1800018129. Date assigned: 31 August 2018. Protocol version: 1.0 (18 July 2017)
The impact of passive heat maintenance strategies between an active warm-up and performance: a systematic review and meta-analysis
Authors: Cowper Gavin , Goodall Stuart , Hicks Kirsty , Burnie Louise , Briggs Marc
Published: August 2022

Background

Prior to exercise, a warm-up routine has been suggested to be an imperative factor in task readiness with the anticipation that it will enhance performance. One of the key benefits of a warm-up is the increase in muscle and core temperature, which can be achieved in a variety of ways. An effective way to achieve improvements in core and muscle temperature is by performing an active warm-up. However, lengthy transition periods between an active warm-up and exercise performance are known to cause a decline in core and muscle temperature, thereby reducing performance capability. As such, methods are needed to assist athletes during transition periods, to maintain the benefits of a warm-up with the aim of optimising performance. Accordingly, the purpose of this review is to systematically analyse the evidence base that has investigated the use of passive heating to aide sporting performance when a transition period is experienced.

Methods

A systematic review and meta-analysis were undertaken following relevant studies being identified using PubMed, Web of Science, and EBSCO. Studies investigating the effects of passive heating strategies during the transition period between an active warm-up and exercise performance were included. The quality of the included studies were assessed by two independent reviewers using a modified version of the Physiotherapy Evidence Database scale.

Results

Seven studies, all high quality (mean = 7.6), reported sufficient data (quality score > 5) on the effects of passive heating strategies on exercise performance, these studies consisted of 85 well-trained athletes (78 male and 7 female). Passive heating strategies used between an active warm-up and exercise, significantly increased peak power output in all studies (ES = 0.54 [95% CI 0.17 to 0.91]). However, only a favourable trend was evident for exercise performance (ES = 1.07 [95% CI − 0.64 to 0.09]).

Conclusions

Based upon a limited number of well-conducted, randomised, controlled trials, it appears that passive heating strategies used between an active warm-up and exercise have a positive impact on peak power output. Although, additional research is necessary to determine the optimum procedure for passive warm-up strategies.
Perspectives and challenges in patient stratification in Alzheimer’s disease
Authors: Abdelnour Carla , Agosta Federica , Bozzali Marco , Fougère Bertrand , Iwata Atsushi , Nilforooshan Ramin , Takada Leonel T. , Viñuela Félix , Traber Martin
Published: August 2022

Background

Patient stratification is the division of a patient population into distinct subgroups based on the presence or absence of particular disease characteristics. As patient stratification can be used to account for the underlying pathology of a disease, it can help physicians to tailor therapeutic interventions to individuals and optimize their care management and treatment regime. Alzheimer’s disease, the most common form of dementia, is a heterogeneous disease and its management benefits from patient stratification in clinical trials, and the development of personalized care and treatment strategies for people living with the disease.

Main body

In this review, we discuss the importance of the stratification of people living with Alzheimer’s disease, the challenges associated with early diagnosis and patient stratification, and the evolution of patient stratification once disease-modifying therapies become widely available.

Conclusion

Patient stratification plays an important role in drug development in clinical trials and may play an even larger role in clinical practice. A timely diagnosis and stratification of people living with Alzheimer’s disease is paramount in determining people who are at risk of progressing from mild cognitive impairment to Alzheimer’s dementia. There are key issues associated with stratifying patients which include the heterogeneity and complex neurobiology behind Alzheimer’s disease, our inadequately prepared healthcare systems, and the cultural perceptions of Alzheimer’s disease. Stratifying people living with Alzheimer’s disease may be the key in establishing precision and personalized medicine in the field, optimizing disease prevention and pharmaceutical treatment to slow or stop cognitive decline, while minimizing adverse effects.
Prevalence of reported food allergies in Brazilian preschoolers living in a small Brazilian city
Authors: da S. Correia José A. , Antunes Adriana Azoubel , Taborda-Barata Luiz , Boechat José Laerte , Sarinho Emanuel Sávio Cavalcanti
Published: August 2022

Introduction

Although the prevalence of allergic diseases, including food allergies, has increased over recent decades, relevant information on this topic is still lacking, particularly in younger children living in small cities.

Objective

To investigate the prevalence of reported food allergies in preschoolers in Limoeiro/Pernambuco, Brazil.

Methods

This was a cross-sectional study with preschoolers. Parents/guardians of all preschoolers enrolled at municipal schools between March and June 2019 (total of 619) were invited to complete a screening questionnaire (total of 619). Another 151 questionnaires were applied on the streets of the town. For positive responses, a second, more detailed and validated questionnaire was completed.

Results

A total of 412 questionnaires were returned, of which, 47 presented a positive response to food allergies and only 29 (7.04%) identified a particular food. The most frequently reported food items were shrimp, mollusks, pork, fruit and milk. Of the 29 who identified foods, 22 responded to the detailed questionnaire, resulting in only 4 (0.97%) positive responses. Of these, two were later discarded through clinical examinations and an open oral provocation test, resulting in a final prevalence of 0.48% of confirmed food allergies.

Conclusion

The prevalence of reported food allergies was lower than that described in previous studies. The most commonly mentioned foods were shrimp, mollusks and pork, with more reports of multiple food allergies, even in children who had never been previously exposed to these possible allergens, which highlights the relevance of perception in reported food allergy studies.
Circular RNA BIRC6 depletion promotes osteogenic differentiation of periodontal ligament stem cells via the miR-543/PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment
Authors: Zhao Xinyuan , Sun Wenjuan , Guo Bing , Cui Li
Published: August 2022

Background

Periodontal ligament stem cells (PDLSCs) are the ideal seed cells for periodontal tissue regeneration. It is well established that persistent inflammation significantly impairs the osteogenic differentiation capability of PDLSCs. Therefore, maintaining PDLSC osteogenic potential under the inflammatory microenvironment is important for treating bone loss in periodontitis. The aim of our study was to explore the potential role of circular RNA BIRC6 (circBIRC6) in regulating osteogenic differentiation of PDLSCs in the inflammatory conditions.

Methods

Alkaline phosphatase staining, Alizarin Red staining, quantitative real-time polymerase chain reaction, western blotting and immunofluorescence staining were used to evaluated the effects of circBIRC6 on the osteogenic differentiation of PDLSCs. RNA pull-down and luciferase assays were performed to explore the interaction between circBIRC6 and miR-543. Then, the downstream signaling pathway affected by circBIRC6/miR-543 axis was further investigated.

Results

The expression level of circBIRC6 was higher in PDLSCs exposed to inflammatory stimulus and in periodontitis tissues compared to the respective controls. Downregulation of circBIRC6 enhanced the osteogenic potential of PDLSCs under the inflammatory conditions, and upregulation of circBIRC6 led to opposite findings. Mechanistically, we found that circBIRC6 modulated PDLSC osteogenic differentiation through sponging miR-543. More importantly, we have demonstrated that circBIRC6/miR-543 axis regulated the mineralization capacity of PDLSCs via PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment.

Conclusions

In summary, the expression of miR-543 is significantly increased following circBIRC6 downregulation, leading to inhibition of PTEN and subsequently activation of PI3K/AKT/mTOR signaling pathway. Therefore, targeting circBIRC6 might represent a potential therapeutic strategy for improving bone loss in periodontitis.
Chemical named entity recognition in the texts of scientific publications using the naïve Bayes classifier approach
Authors: Tarasova O. A. , Rudik A. V. , Biziukova N. Yu. , Filimonov D. A. , Poroikov V. V.
Published: August 2022

Motivation

Application of chemical named entity recognition (CNER) algorithms allows retrieval of information from texts about chemical compound identifiers and creates associations with physical–chemical properties and biological activities. Scientific texts represent low-formalized sources of information. Most methods aimed at CNER are based on machine learning approaches, including conditional random fields and deep neural networks. In general, most machine learning approaches require either vector or sparse word representation of texts. Chemical named entities (CNEs) constitute only a small fraction of the whole text, and the datasets used for training are highly imbalanced.

Methods and results

We propose a new method for extracting CNEs from texts based on the naïve Bayes classifier combined with specially developed filters. In contrast to the earlier developed CNER methods, our approach uses the representation of the data as a set of fragments of text (FoTs) with the subsequent preparati`on of a set of multi-n-grams (sequences from one to n symbols) for each FoT. Our approach may provide the recognition of novel CNEs. For CHEMDNER corpus, the values of the sensitivity (recall) was 0.95, precision was 0.74, specificity was 0.88, and balanced accuracy was 0.92 based on five-fold cross validation. We applied the developed algorithm to the extracted CNEs of potential Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. A set of CNEs corresponding to the chemical substances evaluated in the biochemical assays used for the discovery of Mpro inhibitors was retrieved. Manual analysis of the appropriate texts showed that CNEs of potential SARS-CoV-2 Mpro inhibitors were successfully identified by our method.

Conclusion

The obtained results show that the proposed method can be used for filtering out words that are not related to CNEs; therefore, it can be successfully applied to the extraction of CNEs for the purposes of cheminformatics and medicinal chemistry.