bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced supportive care for advanced cancer patients: study protocol for a randomized controlled trial
Authors: Choi Yun Young , Rha Sun Young , Cho Sungkun , Lee Hye Sun , Hong Bomi , Lee Jiyeon 
Published: December 2022

AbstractBackgroundEarly palliative care along with standard cancer treatments is recommended in current clinical guidelines to improve the quality of life and survival of cancer patients. This study protocol aims to evaluate the effect of “Enhanced Supportive Care”, an early primary palliative care provided by nurses.MethodsA randomized controlled trial (RCT) will be conducted including advanced cancer patients scheduled for first-line palliative chemotherapy (N=360) and their caregivers in South Korea. Participants will be randomly assigned to the intervention or control group in a 1:1 ratio. Participants in the intervention group will receive the “Enhanced Supportive Care”, which provides five sessions of symptom management and coping enhancement counseling by nurses. The control group will receive symptom monitoring five times. The primary endpoints are symptoms, coping, and quality of life (QoL) at 3 months. Secondary endpoints are symptoms, coping, and QoL at 6 months, depression and self-efficacy for coping with cancer at 3 and 6 months, symptom and depression change from baseline to 3 months, survival at 6 and 12 months among patients, and depression among caregivers at 3 and 6 months.DiscussionThis RCT will evaluate the effects of “Enhanced Supportive Care” on symptoms, depression, coping, self-efficacy for coping with cancer, QoL and survival of patients, as well as depression of caregivers. It will provide evidence of a strategy to implement early primary palliative care provided by nurses, which may consequently improve cancer care for newly diagnosed patients with advanced stage cancer.Trial registrationClinicalTrials.gov, NCT04407013. Registered on May 29, 2020,https://www.clinicaltrials.gov/ct2/show/study/NCT04407013. The protocol version is ESC 1.0.
A collaborative care package for depression comorbid with chronic physical conditions in South Africa
Authors: Petersen Inge , Selohilwe One , Georgeu-Pepper Daniella , Ras Christy-Joy , Zani Babalwa , Petrus Ruwayda , Anderson Lauren , Mntambo Ntokozo , Kathree Tasneem , Bhana Arvin , Thornicroft Graham , Fairall Lara 
Published: December 2022

Abstract

Introduction
A task-sharing collaborative care model for integrated depression care for South Africa’s burgeoning primary health care population with chronic conditions was developed and tested through two pragmatic cluster randomized controlled trials. One trial focused on patients with hypertension and was located in one district where a collaborative care model was co-designed with district stakeholders. The other trial, focused on patients on antiretroviral treatment, was located in the same district site, with the addition of a second neighbouring district, without adaptation of the original model. This paper describes the package used to implement this model, and implementation outcomes across the two sites, and summarises lessons and challenges.

Methods
The Template for Intervention Description and Replication (TIDieR) framework, adapted for complex health systems interventions, was used to describe components of the package. Additional elements of ‘modifications made’ and ‘actual implementation’ introduced in the ‘Getting messier with TIDieR’ framework, were used to describe implementation outcomes in terms of reach, adoption and implementation across the two trial districts.

Results
In the absence of a co-design process to adapt the model to the context of the second site, there was less system level support for the model. Consequently, more project employed human resources were deployed to support training of primary care nurses in identification and referral of patients with depression; and supervise co-located lay counsellors. Referrals to co-located lay counselling services were more than double in the second site. However, uptake of counselling sessions was greater in the first site. This was attributed to greater in-vivo supervision and support from existing mental health specialists in the system. There was greater reliance on online supervision and support in the second site where geographical distances between clinics were larger.

Conclusion
The need for in-country co-designed collaborative care models, and ‘implementation heavy’ implementation research to understand adaptations required to accommodate varying in-country health system contexts is highlighted.
The trend and direct costs of screening and chemotherapy treatment of breast cancer in the new coronavirus pandemic: total and interrupted time series study
Authors: Hyeda Adriano , da Costa Élide Sbardellotto Mariano , Kowalski Sérgio Candido 
Published: December 2022

Abstract
Background
The COVID-19 pandemic has overloaded the healthcare systems of many countries and reduced the population’s access to treatment and prevention of other diseases. This study aims to assess whether the COVID-19 pandemic has negatively interfered with the trend and the direct costs of screening and chemotherapy treatment of breast cancer in a public and universal healthcare system.

Method
This was an ecological time series study using an open database of a public and universal health system from 2017 to 2021.

Results
In 2020, there was a 41% reduction in the coverage rate of breast cancer screening in women aged 50 to 69 years (about 1 million mammograms missed). The total direct cost of breast cancer screening reduced proportionally to the number of tests (BRL 67 million). On the other hand, the cost of chemotherapy treatment was higher in 2020, both in advanced (BRL 465 million) and localized (BRL 113 million) diseases. In the time series, mammograms’ trend and direct costs changed from stationary to decreasing after the COVID-19 pandemic. The trend of direct costs with chemotherapy treatment for the advanced disease has been increasing and has not changed after the COVID-19 pandemic. On the other hand, in the case of localized disease, there was a trend toward reducing direct costs after the pandemic.

Conclusion
After COVID-19, there was a downward trend in breast cancer screening and its direct costs, an upward trend in chemotherapy costs for advanced disease, and a downward trend in chemotherapy costs for localized disease.
The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy
Authors: Wang Shiyun , Deng Zixuan , Zhang Hong , Zhang Rong , Yan Dandan , Zheng Xiaojiao , Jia Weiping , Hu Cheng 
Published: December 2022

Abstract
Background
Dimethylarginine dimethylaminohydrolase (DDAH) 1 maintains the bioavailability of nitric oxide by degrading asymmetric dimethylarginine (ADMA). Here, we aimed to investigate the effect of haptoglobin (Hp) genotype on the association of ADMA and DDAH 1 polymorphism with diabetic macroangiopathy.

Methods
In stage 1, 90 Chinese participants with type 2 diabetes were enrolled to measure a panel of targeted metabolites, including ADMA, using tandem mass spectrometry (BIOCRATES AbsoluteIDQ™ p180 kit). In stage 2, an independent cohort of 2965 Chinese patients with type 2 diabetes was recruited to analyze the effect of Hp genotype on the association between DDAH 1 rs233109 and diabetic macroangiopathy. Hp genotypes were detected using a validated assay based on the TaqMan method. DDAH 1 rs233109 was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using the MassARRAY platform.

Results
In stage 1, serum ADMA levels correlated with common Hp genotypes (β ± SE = − 0.049 ± 0.023, P = 0.035), but not with diabetic macroangiopathy (P = 0.316). In stage 2, the distribution of DDAH 1 rs233109 genotype frequencies was 15% (CC), 47% (TC), and 38% (TT), which was in Hardy-Weinberg equilibrium (P = 0.948). A significant Hp genotype by rs 233109 genotype interaction effect on diabetic macroangiopathy was found (P = 0.017). After adjusting for confounders, patients homozygous for rs233109 CC were more likely to develop diabetic macroangiopathy than those carrying TT homozygotes in the Hp 2-2 subgroup [odds ratio = 1.750 (95% confidence interval, 1.101–2.783), P = 0.018].

Conclusion
Hp genotype affects the association between DDAH 1 rs233109 and diabetic macroangiopathy in Chinese patients with type 2 diabetes.
Impact of cervical and global spine sagittal alignment on cervical curvature changes after posterior cervical laminoplasty
Authors: Li Xiang-Yu , Wang Yu , Zhu Wei-Guo , Kong Chao , Lu Shi-Bao 
Published: December 2022

Abstract
Objective
To analyze the correlation between the changes in cervical curvature and the sagittal parameters of spino-pelvic and clinical efficacy after posterior laminoplasty (LP).

Methods
The patients with cervical spondylosis treated with LP from June 2018 to December 2020 were reviewed. The preoperative and follow-up spine full-length films were measured. The measured data included C2–C7 Cobb angle, C2–7 sagittal vertical axis (SVA), T1 slope (T1S), pelvic incidence, sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and C7-SVA. Japanese Orthopaedic Association (JOA) score and neck disability index (NDI) score were recorded before surgery and follow-up.

Results
There were 56 patients in this study. There were no significant differences in spino-pelvic sagittal parameters before and after surgery; however, the JOA score significantly improved. The changes in postoperative cervical lordosis correlated with SS, PT, LL, T1S, and C7-SVA (P < 0.05). Regression analysis showed that T1S and C7-SVA were associated with reducing cervical lordosis (P = 0.021 and P = 0.001, respectively). Patients with larger T1S combined with larger C7-SVA had more cervical lordosis loss, poor JOA improvement, and high postoperative NDI scores (P < 0.001, P = 0.018, and P < 0.001, respectively).

Conclusion
Patients should be examined with full-length spine film before surgery to evaluate the cervical and spino-pelvic sagittal balance. T1S and C7-SVA correlated with changes in cervical sagittal alignment after LP.

Level of evidence
III.
Low-level colonization of methicillin-resistant Staphylococcus aureus in pigs is maintained by slowly evolving, closely related strains in Finnish pig farms
Authors: Verkola Marie , Takala Milla , Nykäsenoja Suvi , Olkkola Satu , Kurittu Paula , Kiljunen Saija , Tuomala Henni , Järvinen Asko , Heikinheimo Annamari 
Published: December 2022

Abstract
Background
Over the past two decades, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has become widely prevalent in pig production in Europe. The carriage status of LA-MRSA is known to vary among individual pigs, but bacterial load in pigs has rarely been studied. We assessed the quantity of LA-MRSA in nasal and skin samples of pigs and investigated the genetic diversity of the strains together with sequenced strains from national surveillance and pathology samples from the Finnish Food Authority. On two farms with assumed MRSA-positive status, farm 1 and farm 2, 10 healthy pigs were sampled three times during 2 weeks from the nares and skin (study A). On farm 1, 54 additional pigs were sampled and from confirmed MRSA-positive animals, 10 were randomly selected and transported to a clean, controlled environment for further sampling (study B). From the samples taken on farms 1 and 2 and in the controlled environment, MRSA was isolated both by direct plating and enrichment on selective media. spa types, multilocus sequence types, staphylococcal cassette chromosome mec types, resistance and virulence genes were determined. Core genome multilocus sequence typing (cgMLST) analysis was performed, including the sequences deriving from the surveillance/pathology samples from the Finnish Food Authority.

Results
All pigs on farm 1 carried LA-MRSA in the nares at all three time points and five pigs on farm 2 at one time point. Nasal quantity varied between 10 and 103 CFU/swab and quantity on the skin between 10 and 102 CFU/swab. In the controlled environment, MRSA was detected in at least one of the nasal samples from each animal. spa type t034 was predominant. cgMLST showed one cluster with minimum allele differences between 0 and 11.

Conclusions
The study shows predominantly low-level carriage (< 103 CFU/swab) of LA-MRSA on farms. In the controlled environment we observed a decline in nasal carriage but constant skin carriage. cgMLST showed that strains of spa type t034 are closely related at the national level.
Percutaneous bone adhesive application for Jones fracture “at-risk” of nonunion or delayed union: a hypothesis
Authors: Ahankoob Niaz , Stahel Vincent P. 
Published: December 2022

Abstract
Background
Bone adhesives have been on the forefront of orthopedic surgery research for decades due to the potential benefit they may have in fracture management. Current publications and research being conducted on bone adhesive could be applied to our current hypothesis for the benefit of a novel minimally invasive treatment option for a select cohort of fractures, Jones fractures. The select fracture’s gold standard of treatment would be nonoperative, but with risk of complications including nonunion and delayed union.

Presentation of hypothesis
We hypothesize that percutaneous application of bone adhesive will provide an additional treatment option for fracture patterns that do not require operative fixation, but would benefit from additional stability. The primary outcome measures would be (1) duration of time required for bony consolidation (defined as 3 of 4 bridging cortices) and (2) duration of absenteeism (inability to work), and pain levels within the first week after the procedure. Secondary outcome measures would be the incidence of nonunion or delayed union. We hypothesize that the select bone adhesive would accelerate bony consolidation, decrease absenteeism, decrease pain levels within the first week after procedure, and decrease the incidence of delayed union and/or nonunion.

Testing of hypothesis
We propose a prospective multicenter, randomized, and open label trial clinical trial to test the bone adhesive via percutaneous injection into acute non-displaced or minimally displaced Jones fractures.

Implications of hypothesis
Bone adhesives are a new frontier in treatment of fractures, currently in laboratory and animal testing phases. The appropriate bone adhesive formula has not been approved for clinical trial use, but the implications of the bone adhesive may go beyond decreased complications and ease of stabilizing a select cohort of closed fractures. With the injectable compound illustrated (Fig. 1), the adhesive could be applied percutaneously in hopes of achieving improved outcomes compared to non-operative treatment. The overall goal of the clinical trial is to provide patients a safe treatment option for improved bone union rates of nonoperative fractures compared to the current gold standard management of the same fracture with earlier pain control, early bony consolidation and lower risk of delayed union/nonunion. The ideal patient population for use of a percutaneous bone adhesive in future studies would be for those with multiple medical comorbidities for whom surgical risks outweigh the benefits, in addition to patients at high risk for nonunion based on fracture pattern or systemic biology.
Hypertension crisis as the first symptom of renovascular hypertension in children
Authors: Xu Lingling , Ba Hongjun , Jiang Xiaoyun , Qin Youzhen 
Published: December 2022

Abstract
Background
Renovascular hypertension (RVH) is one of the main causes of hypertensive crisis (HTN-C). It is characterized by acute onset and severe disease, and early diagnosis and treatment are difficult. The objective was to describe the characteristics of RVH and factors associated with RVH leading to HTN-C in children. At present, there are few clinical studies on RVH in children with large cases in China.

Methods
This study retrospectively analyzed the clinical data of inpatient children with RVH. Patients were divided into non-hypertensive crisis (non-HTN-C) group, and HTN-C group according to the first symptoms and blood pressure. Further, HTN-C were classified as hypertensive urgency (HTN-U) or hypertensive emergency (HTN-E).

Results
Fifty-four pediatric cases (41 boys and 13 girls) were included. 83.3% of the RVH cases were ≥ 6 years old. Three cases were classified into the non-HTN-C group. Of the 51 HTN-C cases, 18 cases were grouped as HTN-U and 33 as HTN-E. The HTN-U group were mainly asymptomatic (50.0%, 9/18) while the HTN-E group mainly presented with neurological symptoms (72.7%, 24/33). The number of unknown etiology children was 32 (59.2%). The top three known etiologies were Takayasu’s arteritis (50.0%, 11/22), congenital renal dysplasia (27.3%, 6/22) and fibromuscular dysplasia (13.6%, 3/22). As for the target organ damage of RVH, patients had a higher prevalence of left ventricular hypertrophy (71.4%, 35/49) and retinopathy (77.8%, 21/27).

Conclusions
Most RVH patients with HTN-C as the first symptoms, especially for males over 6 years old, should be assessed for RVH even if they were asymptomatic. Most asymptomatic patients with RVH already had target organ damage, and symptomatic patients even developed life-threatening complications. As preventive measures, routine monitoring of BP during children’s physical examinations is advised.
Sensitivity of three commercial tests for SARS-CoV-2 serology in children: an Italian multicentre prospective study
Authors: Venturini Elisabetta , Giometto Sabrina , Tamborino Agnese , Becciolini Laura , Bosis Samantha , Corsello Giovanni , Del Barba Paolo , Garazzino Silvia , Lo Vecchio Andrea , Pugi Alessandra , Signa Sara , Stera Giacomo , Trapani Sandra , Castelli Gattinara Guido , Lucenteforte Ersilia , Galli Luisa 
Published: December 2022

Abstract
Background
US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays.

Methods
Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed.
Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value < 0.05 indicated statistical significance.

Results
Overall, 149 children were enrolled in the study. A low sensitivity was found for Diesse IgA, IgM and IgG. Compare to Diesse, Roche S had a higher sensitivity at 15–28 days from infection (0.94, 95%CI: 0.73–1.0) and Roche N at 28–84 days (0.78, 95%CI: 0.58–0.91). When a direct comparison of IgG tests sensitivity was feasible for patients with pairwise information, Roche S and Roche N showed a statistically significant higher sensitivity compared to Diesse in all the study periods, whereas there was no difference between the two Roche tests.

Conclusion
Roche S and Roche N serology tests seem to better perform in children. Large prospective studies are needed to better define the characteristics of those tests.
METTL4-mediated nuclear N6-deoxyadenosine methylation promotes metastasis through activating multiple metastasis-inducing targets
Authors: Hsu Kai-Wen , Lai Joseph Chieh-Yu , Chang Jeng-Shou , Peng Pei-Hua , Huang Ching-Hui , Lee Der-Yen , Tsai Yu-Cheng , Chung Chi-Jung , Chang Han , Chang Chao-Hsiang , Chen Ji-Lin , Pang See-Tong , Hao Ziyang , Cui Xiao-Long , He Chuan , Wu Kou-Juey 
Published: December 2022

Abstract
Background
DNA N6-methyldeoxyadenosine (6mA) is rarely present in mammalian cells and its nuclear role remains elusive.

Results
Here we show that hypoxia induces nuclear 6mA modification through a DNA methyltransferase, METTL4, in hypoxia-induced epithelial-mesenchymal transition (EMT) and tumor metastasis. Co-expression of METTL4 and 6mA represents a prognosis marker for upper tract urothelial cancer patients. By RNA sequencing and 6mA chromatin immunoprecipitation-exonuclease digestion followed by sequencing, we identify lncRNA RP11-390F4.3 and one novel HIF-1α co-activator, ZMIZ1, that are co-regulated by hypoxia and METTL4. Other genes involved in hypoxia-mediated phenotypes are also regulated by 6mA modification. Quantitative chromatin isolation by RNA purification assay shows the occupancy of lncRNA RP11-390F4.3 on the promoters of multiple EMT regulators, indicating lncRNA-chromatin interaction. Knockdown of lncRNA RP11-390F4.3 abolishes METTL4-mediated tumor metastasis. We demonstrate that ZMIZ1 is an essential co-activator of HIF-1α.

Conclusions
We show that hypoxia results in enriched 6mA levels in mammalian tumor cells through METTL4. This METTL4-mediated nuclear 6mA deposition induces tumor metastasis through activating multiple metastasis-inducing genes. METTL4 is characterized as a potential therapeutic target in hypoxic tumors.