bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the effect of different loading doses of phenobarbitone on serum phenobarbitone levels in babies with neonatal seizures and effect of therapeutic hypothermia on phenobarbitone levels
Authors: Palaparthy Vinod , Kumar Manish , Rebekah Grace , Thomas Niranjan 
Published: September 2022

Abstract

Background
With current recommendation for phenobarbitone dosing, we have noted that babies are extremely sedated with elevated serum phenobarbitone levels. We postulate that asphyxiated neonates with hypoxic liver injury have impaired drug metabolism and renal injury affects drug elimination, thus elevating serum drug levels. Therapeutic hypothermia (TH) could further affect the drug levels.

Objective
To determine the serum levels of the phenobarbitone in babies receiving different loading doses of phenobarbitone for neonatal seizures and to study the effect of asphyxia and TH on drug levels.

Design
Prospective observational cohort study.

Material and methods
Term neonates with seizures of any cause were given phenobarbitone up to a maximum loading of 40 mg/kg followed by maintenance dose of 5 mg/kg/day. Serum phenobarbitone levels were assessed after 4 h of the initial loading dose and subsequently at 24, 48 and 72 h from the time after maximum loading dose. Babies were divided into three groups Group 1 (HIE + TH—hypoxic ischemic encephalopathy undergoing TH), Group 2 (HIE − TH—hypoxic ischemic encephalopathy without TH) and Group 3 (non-HIE group).

Results
A total of 47 babies completed the study. Twenty-three (49%) received 20 mg/kg, 14 (30%) received 30 mg/kg and 10 (21%) received 40 mg per kg of phenobarbitone as loading dose. HIE was the major cause of seizures 28 (59%) followed by hypoglycemia 7 (14%), cerebral malformations 4 (8%), inborn errors of metabolism 2 (4%) and hypocalcemia 1 (2%) while the cause of seizures was not known in 6 (13%). Median (IQR) Phenobarbitone levels at 72 h in babies who received 20 mg/kg loading dose of phenobarbitone was 46.72 (44.02–50.49) mcg/ml in HIE + TH group, 40.53 (28.66–65.09) mcg/ml in HIE − TH group and 49 (37–65) mcg/ml in non-HIE group. After a loading dose of 30 mg/kg, phenobarbitone level was 63.76 (59.5–65.94) mcg/ml in HIE + TH group, 42.5 (34.75–48.75) mcg/ml in HIE − TH group and 42.07 (40–49.05) mcg/ml in non-HIE group. After 40 mg/kg loading dose, it was 62.3 (60.2–64.9) mcg/ml in HIE + TH group, 57.0 (49.8–60.2) mcg/ml in HIE − TH group and 48.15 (40.8–50.97) mcg/ml in non-HIE group. In babies who received &gt;20 mg/kg loading dose, 100% of HIE + TH, 80% of HIE − TH and 60% of non-HIE had supratherapeutic levels of phenobarbitone.

Conclusion
At higher loading doses of 30 and 40 mg/kg, steady state concentration of serum phenobarbitone is higher in babies with hypoxic ischemic encephalopathy who underwent TH than in babies with non-HIE causes of seizures. Loading dose beyond 20 mg/kg should be used with close monitoring of serum drug level
The Future of Spine Care Innovation - Software not Hardware: How The Digital Transformation Will Change Spine Care Delivery
Authors: Simpson Andrew K. , Crawford Alexander M. , Striano Brendan M. , Kang James D. , Schoenfeld Andrew J. 
Published: September 2022

Study Design.
Narrative review.

Objective.
To utilize the lessons from the digital transformation of industries beyond healthcare, weigh the changing forces within the healthcare ecosystem, and provide a framework for the likely state of spine care delivery in the future.

Summary of Background Data.
Advances in technology have transformed the way in which we as consumers interact with most products and services, driven by devices, platforms, and a dramatic increase in the availability of digital data. Spine care delivery, and much of healthcare in general, has lagged far behind, hamstrung by regulatory limitations, narrow data networks, limited digital platforms, and cultural attachment to legacy care delivery models.

Methods.
We present a narrative review of the current state of the spine field in this dynamic and evolving environment.

Results.
The past several decades of spine innovation have largely been driven by “hardware” improvements, such as instrumentation, devices, and enabling technologies to facilitate procedures. These changes, while numerous, have largely resulted in modest incremental improvements in clinical outcomes. The next phase of growth in spine care, however, is likely to be more reflective of the broader innovation ecosystem that has already transformed most other industries, characterized by improvements in “software”, including: (1) leveraging data analytics with growing electronic health records databases to optimize interactions between patients and providers, (2) expanding digital and telemedicine platforms to create integrated hybrid service lines, (3) data modeling for patient and provider decision aids, (4) deploying provider and service line performance metrics to improve quality, and (5) movement toward more free market dynamics as patients increasingly move beyond legacy limited health system networks.

Conclusion.
Spine care stakeholders should familiarize themselves with the concepts discussed in this review, as they create value for patients and are also likely to dramatically shift the spine care delivery landscape.
Generalization of pain-related avoidance behavior based on de novo categorical knowledge
Authors: Glogan Eveliina , Gatzounis Rena , Bennett Marc Patrick , Holthausen Katharina , Meulders Ann 
Published: September 2022

Abstract
People with chronic pain often fear and avoid movements and activities that were never paired with pain. Safe movements may be avoided if they share some semantic relationship with an actual pain-associated movement. This study investigated whether pain-associated operant responses (movements) can become categorically associated with perceptually dissimilar responses, thus motivating avoidance of new classes of safe movements—a phenomenon known as category-based avoidance generalization. Using a robotic arm, 2 groups were trained to categorize arm movements in different ways. Subsequently, the groups learned through operant conditioning that an arm movement from one of the categories was paired with a high probability of pain, whereas the others were paired with either a medium probability of pain or no pain (acquisition phase). Self-reported pain-related fear and pain expectancy were collected as indices of fear learning. During a final generalization test phase, the movements categorically related to those from the acquisition phase were made available but in the absence of pain. Results showed that the generalization of outcome measures depended on the categorical connections between arm movements, ie, the groups avoided and feared the novel generalization movement categorically related to the pain-associated acquisition movement, depending on how they had previously learned to categorize the movements. This suggests that operant pain-related avoidance can generalize to safe behaviors, which are not perceptually, but categorically, similar to a pain-associated behavior. This form of pain-related avoidance generalization is problematic because category-based relations can be extremely wide reaching and idiosyncratic. Thus, category-based generalization of operant pain-related avoidance merits further investigation.
Meta-analysis of the effect of sodium-dependent glucose transporter 2 inhibitors on C-reactive protein in type 2 diabetes
Authors: Sun Wenwen , Xing Yuling , Kong Dexian , Zhang Zhimin , Ma Huijuan , Yang Linlin 
Published: September 2022

Background:
As novel hypoglycemic drugs, the effects of sodium-dependent glucose transporter 2 inhibitors (SGLT-2I) on inflammatory factors such as C-reactive protein (CRP) remain unclear.

Methods:
We conducted a meta-analysis of studies on SGLT-2I in the treatment of type 2 diabetes (T2DM) to observe the changes of CRP in patients with T2DM. We searched 4 electronic databases (CNKI, PubMed, EMBASE, and Cochrane Library) for articles published up to December 31, 2021. Studies were analyzed using a random-effects model to obtain standard deviation mean differences (SMDs) and 95% confidence intervals (CIs). Sensitivity and subgroup analyses were performed. Publication bias was evaluated using funnel plots and Egger test.

Results:
We included data from 927 patients in 13 confirmatory trials that showed a significant decrease in CRP among patients with T2DM treated with SGLT-2I. The decrease was more significant with than without SGLT-2I. In subgroup analysis according to nationality, medication, and comorbidities, CRP reduction was associated with nationality, SGLT-2I type, and the presence of comorbidities. Sensitivity analysis showed that our results were reliable and found no evidence of substantial publication bias.

Conclusions:
SGLT-2I could reduce CRP levels in patients with T2DM.

Registration:
International Prospective Register for Systematic Reviews (PROSPERO) number CRD42021268079.
Laparoscopic radical nephroureterectomy in the oblique supine lithotomy integrative position for rare renal malignant perivascular epithelioid cell tumor with renal vein cancerous thrombosis: A case report and literature review
Authors: Lin Canbin , Liang Shulin , Wang Yongxing , Liang Aidi , Qin Weiting , Huang Jiapeng , Meng Hao , Liu Hong , Chen Ming , Meng Lei 
Published: September 2022

Rationale:
Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor that arises from perivascular epithelioid cells and can differentiate into melanocytes and smooth muscle cells. Malignant renal perivascular epithelioid cell tumor is extremely rare. Due to the lack of specific clinical manifestations and imaging features, diagnosing PEComa depends on postoperative pathology and immunohistochemistry. Surgery is the primary treatment for malignant PEComa because the efficacy of radiotherapy and chemotherapy is uncertain. There is still a lack of unified diagnostic criteria and treatment guidelines for renal malignant PEComa, especially with vascular invasion. Hence, the treatment experience depends on a small number of cases reported worldwide.

Patient concerns:
A 68-year-old woman was admitted to our hospital due to intermittent hematuria for over 8 months. The color Doppler ultrasound and computed tomography scan revealed a mass in the lower middle part of the left kidney.

Diagnosis:
Rare renal malignant perivascular epithelioid cell tumor with renal vein cancerous thrombosis.

Interventions:
A laparoscopic radical left nephroureterectomy in the oblique supine lithotomy position was performed.

Outcomes:
The operation process went smoothly, and no pulmonary embolism occurred after the operation. The final pathological diagnosis was a renal malignant perivascular epithelioid cell tumor. After a 12-month follow-up, no recurrence or metastasis was found.

Lessons:
Renal malignant PEComa is an extremely rare mesenchymal tumor diagnosed mainly based on pathology. Surgery is currently the effective treatment for malignant PEComa. For the surgical treatment of malignant renal PEComa with vascular invasion, laparoscopic radical nephroureterectomy in the oblique supine lithotomy integrative position has many benefits, as exemplified by our current case.
Using the Sankey diagram to visualize article features on the topics of whole-exome sequencing (WES) and whole-genome sequencing (WGS) since 2012: Bibliometric analysis
Authors: Li Meng-Ju , Chien Tsair-Wei , Liao Kuang-Wen , Lai Feng-Jie 
Published: September 2022

Background:
Sequencing technologies, such as whole-exome sequencing (WES) and whole-genome sequencing (WGS), have been increasingly applied to medical research in recent years. Which countries, journals, and institutes (called entities) contributed most to the fields (WES/WGS) remains unknown. Temporal bar graphs (TBGs) are frequently used in trend analysis of publications. However, how to draw the TBG on the Sankey diagram is not well understood in bibliometrics. We thus aimed to investigate the evolution of article entities in the WES/WGS fields using publication-based TBGs and compare the individual research achievements (IRAs) among entities.

Methods:
A total of 3599 abstracts downloaded from icite analysis were matched to entities, including article identity numbers, citations, publication years, journals, affiliated countries/regions of origin, and medical subject headings (MeSH terms) in PubMed on March 12, 2022. The relative citation ratio (RCR) was extracted from icite analysis to compute the hT index (denoting the IRA, taking both publications and citations into account) for each entity in the years between 2012 and 2021. Three types of visualizations were applied to display the trends of publications (e.g., choropleth maps and the enhanced TBGs) and IRAs (e.g., the flowchart on the Sankey diagram) for article entities in WES/WGS.

Results:
We observed that the 3 countries (the US, China, and the UK) occupied most articles in the WES/WGS fields since 2012, the 3 entities (i.e., top 5 journals, research institutes, and MeSH terms) were demonstrated on the enhanced TBGs, the top 2 MeSH terms were genetics and methods in WES and WGS, and the IRAs of 6 article entities with their hT-indices were succinctly and simultaneously displayed on a single Sankey diagram that was never launched in bibliographical studies.

Conclusion:
The number of WES/WGS-related articles has dramatically increased since 2017. TBGs, particularly with hTs on the Sankey, are recommended for research on a topic (or in a discipline) to compare trends of publications and IRAs for entities in future bibliographical studies.
MicroRNA34a is associated with chemotherapy resistance, metastasis, recurrence, survival, and prognosis in patient with osteosarcoma
Authors: Lian Hongyu , Zhou Yang , Sun Zhang , Liu Kexin 
Published: September 2022

Background:
Osteosarcoma (OS) is the primary malignant bone tumor that most commonly affects children, adolescents, and young adults. MicroRNA-34a (miR-34a) is involved in tumor metastasis and may be a prognostic marker for patients with cancer. The aim of the present study was to explore the role of miR-34a in patients with OS. The underlying associations between miR-34a expressions and metastasis, recurrence as well as and prognosis were comprehensively analyzed in OS patients.

Methods:
Reverse transcriptase quantitative PCR (RT-qPCR) was used to investigate serum level of miR-34a between clinical OS patients (n = 162) and age-matched healthy controls (n = 162). Expression of miR-34a in OS tissues and adjacent tissues was analyzed using RT-qPCR. RT-qPCR was used to compare the serum level of miR-34a in patients with OS before and after chemotherapy. Multivariate Cox-regression analysis was used to analyze the association between serum level of miR-34a and chemotherapy resistance, overall survival, as well as recurrence and prognosis of OS patients. Five-year recurrence and survival were estimated using Kaplan–Meier curves.

Results:
Serum level of miR-34a was downregulated in OS patients (n = 86) compared to age-matched healthy controls (n = 86). Expression of miR-34a was downregulated in OS tissue compared to adjacent tissues in clinical patients. The expression of serum miR-34a before and after chemotherapy was positively correlated with the expression of miR-34a in the corresponding tissues. Expression of miR-34a was higher in the group where chemotherapy was effective than that patient where chemotherapy was ineffective. Expression of miR-34a was negatively associated with chemotherapy resistance of OS patients. High serum levels of miR-34a were associated with longer overall survival in OS patients and lower metastasis. Multivariate Cox-regression analysis identified miR-34a serum level with potential prognostic significance.

Conclusion:
The expression level of serum miR-34a in patients with OS is closely related to the chemotherapy resistance, metastasis, recurrence, and survival of osteosarcoma, which can be used as one of the potential biomarkers and prognosis for the treatment of OS patients. Therefore, miR-34a may be a potential molecular for prediction of the efficacy of chemotherapy and prognosis in OS patients.
Hereditary neuropathy with liability to pressure palsies misdiagnosed as Guillain–Barré Syndrome: A case report
Authors: Zhu Jianming , Tong Xueqing , Li Yandeng , Li Guangqin , Pi Zhendong 
Published: September 2022

Rationale:
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited genetic disease characterized by recurrent numbness and limb weakness. HNPP can be easily missed or misdiagnosed because of electrophysiological heterogeneity and atypical clinical symptoms. To date, diagnosis of HNPP remains a challenge for clinicians.

Patient concerns:
Here, we report the case of a 12-year-old woman diagnosed with HNPP, which was initially diagnosed with Guillain–Barré Syndrome (GBS) and treated with intravenous immunoglobulin (IVIG).

Diagnoses:
Repeat electrodiagnostic studies and genetic testing confirmed the diagnosis of HNPP.

Interventions:
The patient was treated with neurotrophic drugs and health education, including avoiding maintenance of a certain posture for extended periods, which could damage the peripheral nerves.

Outcomes:
The patient was discharged 5 days later. The patient was free from recurrence after 6 months of follow-up.

Lessons:
This case highlights the complexity of HNPP diagnosis and emphasizes the importance of early identification.
Intensity control of robot-assisted gait training based on biometric data: Preliminary study
Authors: Jiae Kim , Chun Min Ho , Lee Junekyung , Kim Jun Won , Lee Ji Yeon 
Published: September 2022

Objective:
This study is aimed to compare the effect of robot-assisted gait training when the intensity is controlled using patients’ biometric data to when controlled by therapist’s subjective judgment.

Design:
This is non-blinded, prospective, randomized controlled study. Patients were randomly assigned to one of two groups. In biometric data control group, exercise intensity was controlled through the patient’s heart rate or rating of perceived exertion (RPE). The intensity was raised to the next level when the patient’s heart rate reserve was less than 40 percent or the RPE was less than 12 points. The exercise intensity of the therapist control group was adjusted according to the judgement of a therapist. All patients were instructed to perform robot (Morning Walk®)-assisted 20-minute gait training session five times a week during 3 weeks. The primary outcome was functional ambulation category (FAC). The secondary outcomes were modified Barthel index (MBI), Berg balance scale (BBS), timed up and go test (TUG) and 10-meter walk test (10MWT) The outcomes were evaluated at baseline and after 3-week gait training.

Results:
A total of 55 patients with stroke were enrolled. After robotic rehabilitation, the primary outcome, FAC improved significantly (P < .05) in both groups. Also, secondary outcomes, including MBI, BBS, TUG, 10MWT, showed significant improvement (P < .05) in all groups. In addition, when comparing the functional change from baseline to week 3 between the two groups, there was no statistically significant difference in FAC (P > .05). The difference of baseline and week 3 of secondary outcome measure, MBI, BBS, TUG, 10MWT, showed no significant difference (P > .05).

Conclusion:
In conclusion, when the robot intensity was adjusted using the patient’s heart rate or RPE, the treatment effect has no significant difference to when adjusting the intensity according to the know-how of the therapist.
Community-based newborn care intervention fidelity and its implementation drivers in South Wollo Zone, North-east Ethiopia
Authors: Molla Asressie , Mekonnen Solomon , Tigabu Zemene , Alemu Kassahun , Gebeyehu Abebaw 
Published: September 2022

AbstractIntroductionCommunity-based newborn care (CBNC) is an effective and efficient public health intervention that has been implemented in Ethiopia across the maternal, neonatal, and child health continuum of care with the goal of lowering newborn death. But Ethiopian neonatal mortality rate is among the highest in the world. “Why neonatal mortality still high despite the existence of such effective interventions?” is the question. Thus, authors hypothesize that whether the designed intervention is effectively implemented or not is not known. Therefore, the aim of this study is to investigate community-based newborn care intervention fidelity and its implementation drivers.MethodsMulticenter community-based cross-sectional study mixed with phenomenological qualitative design was employed on 898 postpartum women, 16 health extension workers (HEWs) and 10 health posts were used to evaluate CBNC. Structured questionnaire and facility audit checklist was used to collect quantitative data. In-depth interview technique was used to explore lived experiences of HEWs on CBNC implementation. CBNC intervention fidelity was computed as a composite index of the product of program coverage, frequency and contents.Multilevel linear regression model with adjusted β-coefficients at P-value of 0.05 and a 95% confidence interval (CI) were used to declare a significant relation between CBNC intervention fidelity and its implementation drivers. Interpretative phenomenological analysis was employed for qualitative data analysis.ResultCBNC intervention fidelity was 4.5% (95% CI: 3.6 - 5.4) with only two women received the intervention with full fidelity. The overall CBNC intervention coverage was 38.4% (95% CI: 35.2-41.6). Only 8.1 % and 1.5% of women received all CBNC interventions with recommended frequency and content, respectively. HEWs knowledge of danger sign was significant facilitator while lack of: health center’s feedback, related short-term training, health development army support, health center staff’s technical assistance to HEWs and shortage of medical equipment supply were barriers for CBNC intervention fidelity.ConclusionThe CBNC intervention fidelity was too low to in this study. This indicates that CBNC intervention package was not implemented as envisioned implying an implementation gap. All implementation drivers were poorly implemented to result in improved fidelity and intervention outcomes.