bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of acute otitis media from 2003 to 2019 in children ≤ 17 years in England
Authors: Mohanty Salini , Podmore Bélène , Cuñado Moral Ana , Weiss Thomas , Matthews Ian , Sarpong Eric , Méndez Ignacio , Qizilbash Nawab 
Published: January 2023

Abstract
Background
The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the UK. PCVs are active immunization for the prevention of invasive disease, pneumonia and acute otitis media (AOM) caused by Streptococcus pneumoniae in children.
The aim of this observational study was to estimate incidence rates (IRs) of AOM in children ≤17 years from 2003 to 2019 in England, before and after the introduction of pneumococcal conjugate vaccines (PCVs).

Methods
AOM episodes were identified using Read diagnosis codes in children aged ≤17 years in the Clinical Practice Research Datalink (CPRD) Gold database from 2003 to 2019. Annual IRs with 95% confidence intervals (CI) by age group were calculated as the number of episodes/person-years (PY) at risk. Interrupted time series analyses were conducted to estimate incidence rate ratios (IRR) across post-PCV7 (2007–2009), early post-PCV13 (2011–2014) and late post-PCV13 (2015–2019) periods compared to the pre-PCV7 period (2003–2005) using generalized linear models.

Results
From 2003 to 2019, 274,008 all-cause AOM episodes were identified in 1,500,686 children. The overall AOM IR was 3690.9 (95% CI 3677.1-3704.8) per 100,000 PY. AOM IRs were highest in children aged < 5 years and decreased by age; < 2 years: 8286.7 (95% CI 8216.8-8357.1); 2–4 years: 7951.8 (95% CI 7902.5-8001.4); 5–17 years: 2184.4 (95% CI 2172.1–2196.8) (per 100,000 PY). Overall AOM IRs declined by 40.3% between the pre-PCV7 period and the late-PCV13 period from 4451.9 (95% CI 4418.1-4485.9) to 2658.5 (95% CI 2628.6-2688.7) per 100,000 PY, and across all age groups. IRRs indicated a significant decrease in AOM IRs in all the post-vaccination periods, compared to the pre-PCV7 period: post-PCV7 0.87 (95% CI 0.85–0.89), early post-PCV13 0.88 (95% CI 0.86–0.91), and late post-PCV13 0.75 (95% CI 0.73–0.78).

Conclusions
The AOM IRs declined during the 2003–2019 period; however, the clinical burden of AOM remains substantial among children ≤17 years in England.
Development of a prognostic nomogram for sepsis associated-acute respiratory failure patients on 30-day mortality in intensive care units: a retrospective cohort study
Authors: Luo Mengdi , He Qing 
Published: January 2023

Abstract
Background
Acute respiratory failure is a type of sepsis complicated by severe organ failure. We have developed a new nomogram for predicting the 30-day risk of death in patients through a retrospective study.

Method
Data was collected and extracted from MIMICIV, with 768 eligible cases randomly assigned to the primary cohort (540) and the validation cohort (228). The final six factors were included by Cox regression analysis to create the Nomogram, the accuracy of the Nomogram was assessed using the C-index and calibration curve, and finally, the clinical usefulness of the Nomogram was evaluated using DCA in.

Results
Multivariate Cox regression analysis showed that age, DBP, lactate, PaO2, platelet, mechanical ventilation were independent factors for 30-day mortality of SA-ARF. The nomogram established based on the six factors. The C-index of nomogram in the primary cohort is 0.731 (95% CI 0.657–0.724) and 0.722 (95%CI 0.622–0.759) in the validation cohort. Besides, the decision curve analysis (DCA) confirmed the clinical usefulness of the nomogram.

Conclusion
The study developed and validated a risk prediction model for SA-ARF patients that can help clinicians reasonably determine disease risk and further confirm its clinical utility using internal validation.
Magnitude of undernutrition and associated factors among adult tuberculosis patients attending public health facilities in Haramaya District, Eastern Ethiopia
Authors: Tadesse Fasika , Mitiku Habtamu , Girma Sagni , Kenay Abera 
Published: January 2023

Abstract
Background
Tuberculosis is one of the top ten causes of illness, death, and disability throughout the world. Undernutrition reduces immunity, which makes latent tuberculosis more likely to become active tuberculosis. Tuberculosis makes these conditions worse. The body of a person suffering from TB has an increased demand for energy, which often causes a TB patient to lose a significant amount of weight and this can worsen acute undernutrition. The aim of this study was to assess the magnitude of undernutrition and its associated factors among adult TB patients in public health facilities in Haramaya district, eastern Ethiopia.

Methods
Institution-based cross-sectional study was conducted among 330 adult tuberculosis patients on follow-up in public health facility of Haramaya District, eastern Ethiopia from January 10, 2021 to February 20, 2021. An anthropometric assessment was done after a face-to-face interview using a pretested structured questionnaire. SPSS 24 was used to analyze the data. Bivariable and multivariable logistic regression model was used to identify factors associated with undernutrition.

Results
The overall prevalence of undernutrition was 43.6% (95% CI 38.2–49.1%). Proportion of severe, moderate and mild undernutrition was 11.8%, 12.4%, and 19.4%, respectively. Age group of 18–24 years (AOR = 4.12; 95% CI 1.36–12.51), not have formal education (AOR = 1.76; 95% CI 1.01–3.08), having large family size (AOR = 2.62; 95% CI 1.43–4.82), low dietary diversity (AOR = 2.96; 95% CI 1.75–4.99), lack of latrine (AOR = 2.14; 95% CI 1.26–3.65), history of TB treatment (AOR = 2.56; 95% CI 1.19–5.54) and taking intensive phase of anti-TB drugs (AOR = 3.18; 95% CI 1.62–6.25) were factors found significantly associated with under nutrition.

Conclusion
The prevalence of undernutrition was high. Age, educational status, family size, dietary diversity, toilet facility, history of tuberculosis medication and intensive phase of anti-TB drugs were found significantly associated with undernutrition. The nutritional derangement could call for fast nutritional intervention in the management of pulmonary tuberculosis patients.
Development and validation of a nomogram for survival prediction in hepatocellular carcinoma after partial hepatectomy
Authors: Lu Yang , Ren Shuang , Jiang Jianning 
Published: January 2023

Abstract
Background
The prognosis for hepatocellular carcinoma (HCC) is complex due to its high level of heterogeneity, even after radical resection. This study was designed to develop and validate a prognostic nomogram for predicting the postoperative prognosis for HCC patients following partial hepatectomy.

Patients and methods
We extracted data on HCC patients and randomly divided them into two groups (primary and validation cohorts), using the Surveillance, Epidemiology and End Results (SEER) database. We developed the prediction model based on the data of the primary cohort and prognostic factors were evaluated using univariate and multivariate Cox regression analysis. A nomogram was constructed for predicting the 1-, 3-, and 5-year survival probability of HCC patients after surgery based on the results of the multivariate Cox regression analysis. The performance of the nomogram was evaluated in terms of its discrimination and calibration. To validated the model, discrimination and calibration were also evaluated in the validation cohort. Decision curve analysis (DCA) was performed to assess the clinical utility of the nomogram.

Results
A total of 890 patients who underwent partial hepatectomy for HCC were included in the study. The primary cohort enrolled 628 patients with a median follow-up time of 39 months, the 1-, 3-, and 5-year survival rate were 95.4%, 52.7% and 25.8% during follow-up. Multivariate Cox regression analysis showed that differentiation, tumor size, AFP and fibrosis were independently association with the prognosis of HCC patients after partial hepatectomy. The nomogram showed a moderate discrimination ith a C-index of 0.705 (95% CI 0.669 to 0.742), and good calibration. Similar discrimination with a C-index of 0.681 (95% CI 0.625 to 0.737), and calibration were also observed in the validation cohort. Decision curve analysis showed that the nomogram could be useful to predicting the prognosis in HCC patients following partial hepatectomy.

Conclusions
The proposed nomogram is highly predictive and has moderate calibration and discrimination, potentially contributing to the process of managing HCC patients after partial hepatectomy in an individualized way.
Perceptions of medical students towards the role of histology and embryology during curricular review
Authors: Carneiro Bruno Daniel , Pozza Daniel Humberto , Tavares Isaura 
Published: January 2023

AbstractBackgroundThe continuous changes in the medical education to prepare medical doctors for the future requires updates in medical curriculum. However, the perspectives of the medical students are not frequently considered during the revision of the medical curriculum. In parallel with the process of defining and adjusting the medical curriculum, a large survey was performed to inquire the perspectives of the medical students at the Faculty of Medicine of the University of Porto (FMUP), Portugal, about the role of Histology and of Embryology.MethodsMedical students at FMUP (Portugal) completed a structured and anonymous online questionnaire about the subjects Histology and Embryology. The questionnaire was prepared using questions of previous surveys performed in Europe, including another Portuguese medical school, and additional questions that were specifically prepared to this study. The questions referred to teaching methods, clinical relevance, use of virtual (digital) microscopes and association of Histology and Embryology with other subjects of the medical curriculum.ResultsFour hundred and sixty-two students participated in the study. The students in clinical years were more likely to recognise the clinical relevance of Histology (p = 0.016) and Embryology (p < 0.001). Students agree that teaching of these subjects would benefit from a clinical orientation (89% for Histology; 90% for Embryology). Students highlighted that Histology is crucial to understand Biopathology and agree (75%) that an integration of Histology with Biopathology could be considered in the medical curriculum. Most students (55%) agree that slide microscopes are more useful than virtual microscopes.ConclusionsOur study contributes to the debate about the evolution of medical curriculum. Gathering the medical students’ perceptions using large surveys such as that performed in the present study may be useful to adapt the methods of teaching which may increase the motivation of the students. In the case of Histology and Embryology at the FMUP (Portugal) providing more clinically oriented teaching may be useful to motivate the students. Students of clinical years have strong clinical perspectives of Histology and Embryology and their enrolment in teaching of Histology and Embryology can also contribute to increase motivation of younger students. Consulting and involving medical students in the development of the medical curriculum can be positive and students should be more responsible and engaged in building their own education.
Detection and description of a novel Psychrobacter glacincola infection in some Red Sea marine fishes in Hurghada, Egypt
Authors: El-Sayed Mohamed Raafat , Emam Arafah M. , Osman Ahmed Elsayed , Abd El-Galil Mohamed Abd El-Aziz Ahmed , Sayed Haitham Helmy 
Published: January 2023

AbstractAn important food-producing sector in Egypt is aquaculture and fisheries; however, several pathogenic microorganisms lead to high mortalities and significant economic losses. The occurrence ofPsychrobacter glacincolainfection among 180 wild marine fishes collected from the Red sea at Hurghada, Egypt were investigated in the present study. The disease prevalence rate was 6.7%. The recovered isolates were subjected to biochemical and molecular identification. The study also investigated pathogenicity and the antibiogram profile of the recovered isolates. The clinical examination of the infected fish revealed various signs that included lethargy and sluggish movement, hemorrhages and ulcers on the body and the operculum, scale loss, and fin congestion and rot, especially at the tail fin. Furthermore, during postmortem examination, congestion of the liver, spleen, and kidney was observed. Interestingly, 12 isolates were recovered and were homogenous bacteriologically and biochemically. The phylogenetic analysis based on 16S rRNA gene confirmed that MRB62 identified strain was closely related the genus Psychrobacter and identified asP. glacincolaand was pathogenic toRhabdosargus haffarafish, causing 23.3% mortality combined with reporting a series of clinical signs similar to that found in naturally infected fishes. The present study also showed thatP. glacincolaisolates were sensitive to all antibiotics used for sensitivity testing. Our findings add to the body of knowledge regarding the occurrence of pathogenicP. glacincolainfection in Egyptian marine fishes and its potential effects on fish. Future large-scale surveys exploring this bacterium among other freshwater and marine fishes in Egypt would be helpful for the implementation of effective strategies for the prevention and control of this infection are warranted.
Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model
Authors: Xu Yinlan , Wan Shuangxiu , Sun Panpan , Khan Ajab , Guo Jianhua , Zheng Xiaozhong , Sun Yaogui , Fan Kuohai , Yin Wei , Li Hongquan , Sun Na 
Published: January 2023

AbstractBackgroundPorcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days.ResultsThe synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.ConclusionsThe synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.
Outcomes of deferred revascularisation following negative fractional flow reserve in diabetic and non-diabetic patients: a meta-analysis
Authors: Ekmejian Avedis , Sritharan Hari , Selvakumar Dinesh , Venkateshka Venkateshka , Allahwala Usaid , Ward Michael , Bhindi Ravinay 
Published: January 2023

Abstract
Background
Fractional Flow Reserve (FFR) is a widely applied invasive physiological assessment, endorsed by major guidelines to aid in the decision to perform or defer revascularisation. While a threshold of  > 0.8 has been applied universally, clinical outcomes may be affected by numerous factors, including the presence of diabetes. This meta-analysis aims to investigate the outcomes of diabetic versus non-diabetic patients in whom revascularisation was deferred based on negative FFR.

Methods
We performed a meta-analysis investigating the outcomes of diabetic and non-diabetic patients in whom revascularisation was deferred based on negative FFR. A search was performed on MEDLINE, PubMed and EMBASE, and peer-reviewed studies that reported MACE for diabetic and non-diabetic patients with deferred revascularisation based on FFR  > 0.8 were included. The primary end point was MACE.

Results
The meta-analysis included 7 studies in which 4275 patients had revascularisation deferred based on FFR > 0.8 (1250 diabetic). Follow up occurred over a mean of 3.2 years. Diabetes was associated with a higher odds of MACE (OR = 1.66, 95% CI 1.35–2.04, p =  < 0.001), unplanned revascularisation (OR = 1.48, 95% CI 1.06–2.06, p = 0.02), all-cause mortality (OR = 1.74, 95% CI 1.20–2.52, p = 0.004) and cardiovascular mortality (OR = 2.08, 95% CI 1.07–4.05, p = 0.03).

Conclusions
For patients with stable coronary syndromes and deferred revascularisation based on FFR > 0.8, the presence of diabetes portends an increased long-term risk of MACE compared to non-diabetic patients.
Trail registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022367312.
CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances
Authors: Maalej Karama Makni , Merhi Maysaloun , Inchakalody Varghese P. , Mestiri Sarra , Alam Majid , Maccalli Cristina , Cherif Honar , Uddin Shahab , Steinhoff Martin , Marincola Francesco M. , Dermime Said 
Published: January 2023

AbstractIn the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.
Stop GnRH-agonist/GnRH-antagonist protocol: a different insight on ovarian stimulation for IVF
Authors: Orvieto Raoul 
Published: January 2023

AbstractOvarian stimulation (OS) is one of the key factors in the success of in vitro fertilization-embryo transfer (IVF-ET), by enabling the recruitment of numerous healthy fertilizable oocytes and, thereby, multiple embryos. The Stop GnRH-agonist/GnRH-antagonist (GnRH-ag/GnRH-ant), which offers all the advantages of using long suppressive GnRH-ag, with GnRH-ant, is in my opinion a valuable addition to the armamentarium of OS protocols. It allows cycle programming, better follicular synchronization and offers successful outcome in a variety of challenging cases such as poor responders, Poseidon group 4 poor prognosis patients, those with elevated peak progesterone (P) serum levels, poor embryo quality or repeated IVF failures.
Mechanical performance of porous biomimetic intervertebral body fusion devices: an in vitro biomechanical study
Authors: Tsuang Fon-Yih , Li Ming-Jun , Chu Po-Han , Tsou Nien-Ti , Sun Jui-Sheng 
Published: January 2023

Abstract
Background
Degenerative disc disease is one of the most common ailments severely affecting the quality of life in elderly population. Cervical intervertebral body fusion devices are utilized to provide stability after surgical intervention for cervical pathology. In this study, we design a biomimetic porous spinal cage, and perform mechanical simulations to study its performances following American Society for Testing and Materials International (ASTM) standards before manufacturing to improve design process and decrease cost and consumption of material.

Methods
The biomimetic porous Ti-6Al-4 V interbody fusion devices were manufactured by selective laser melting (laser powder bed fusion: LPBF in ISO/ASTM 52900 standard) and subsequently post-processed by using hot isostatic pressing (HIP). Chemical composition, microstructure and the surface morphology were studied. Finite element analysis and in vitro biomechanical test were performed.

Findings
The post heat treatment can optimize its mechanical properties, as the stiffness of the cage decreases to reduce the stress shielding effect between two instrumented bodies. After the HIP treatment, the ductility and the fatigue performance are substantially improved. The use of HIP post-processing can be a necessity to improve the physical properties of customized additive manufacturing processed implants.

Interpretation
In conclusion, we have successfully designed a biomimetic porous intervertebral device. HIP post-treatment can improve the bulk material properties, optimize the device with reduced stiffness, decreased stress shielding effect, while still provide appropriate space for bone growth.

Clinical significance
The biomechanical performance of 3-D printed biomimetic porous intervertebral device can be optimized. The ductility and the fatigue performance were substantially improved, the simultaneously decreased stiffness reduces the stress shielding effect between two instrumented bodies; while the biomimetic porous structures provide appropriate space for bone growth, which is important in the patients with osteoporosis.