bluuebunny/crossref_metadata_2025_split huggingface dataset:
The natural history study of preclinical genetic Creutzfeldt-Jakob Disease (CJD): a prospective longitudinal study protocol
Authors: Bregman Noa , Shiner Tamara , Kavé Gitit , Alcalay Roy , Gana-Weisz Mali , Goldstein Orly , Glinka Tal , Aizenstein Orna , Bashat Dafna Ben , Alcalay Yifat , Mirelman Anat , Thaler Avner , Giladi Nir , Omer Nurit 
Published: April 2023

Abstract
Background
Creutzfeldt-Jakob Disease (CJD) is the most common prion disease in humans causing a rapidly progressive neurological decline and dementia and is invariably fatal. The familial forms (genetic CJD, gCJD) are caused by mutations in the PRNP gene encoding for the prion protein (PrP). In Israel, there is a large cluster of gCJD cases, carriers of an E200K mutation in the PRNP gene, and therefore the largest population of at-risk individuals in the world. The mutation is not necessarily sufficient for the formation and accumulation of the pathological prion protein (PrPsc), suggesting that other, genetic and non-genetic factors affect the age at symptoms onset. Here we present the protocol of a cross-sectional and longitudinal natural history study of gCJD patients and first-degree relatives of gCJD patients, aiming to identify biological markers of preclinical CJD and risk factors for phenoconversion.

Methods
The study has two groups: Patients diagnosed with gCJD, and first-degree healthy relatives (HR) (both carriers and non-carriers of the E200K mutation in the PRNP gene) of patients diagnosed with gCJD. At baseline, and at the end of every year, healthy participants are invited for an “in-depth” visit, which includes a clinical evaluation, blood and urine collection, gait assessment, brain MRI, lumbar puncture (LP), and Polysomnography (PSG). At 6 months from baseline, and then halfway through each year, participants are invited for a “brief” visit, which includes a clinical evaluation, short cognitive assessment, and blood and urine collection. gCJD patients will be invited for one “in-depth” visit, similar to the baseline visit of healthy relatives.

Discussion
This continuous follow-up of the participants and the frequent assessments will allow early identification and diagnosis in case of conversion into disease. The knowledge generated from this study is likely to advance the understanding of the underlying clinicopathological processes that occur at the very beginning of CJD, as well as potential genetic and environmental risk factors for the development of the disease, therefore advancing the development of safe and efficient interventions.

Trial registration
The study is an observational study. It has registered retrospectively in https://clinicaltrials.gov/ and has been assigned an identification number NCT05746715.
Symptom management care pathway adaptation process and specific adaptation decisions
Authors: Vettese Emily , Sherani Farha , King Allison A. , Yu Lolie , Aftandilian Catherine , Baggott Christina , Agarwal Vibhuti , Nagasubramanian Ramamoorthy , Kelly Kara M. , Freyer David R. , Orgel Etan , Bradfield Scott M. , Kyono Wade , Roth Michael , Klesges Lisa M. , Beauchemin Melissa , Grimes Allison , Tomlinson George , Dupuis L. Lee , Sung Lillian 
Published: April 2023

Abstract
Background
There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions.

Methods
Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications.

Results
Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection.

Conclusions
Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes.

Trial registration
clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1.
Pulmonary tumor thrombotic microangiopathy during good response to immuno-chemotherapy for advanced non-small cell lung cancer: a case report
Authors: Utsu Yoshikazu , Kawakami Makio , Arai Hironori , Hisamatsu Haruka , Yano Yudai , Terada Jiro 
Published: April 2023

Abstract
Background
Pulmonary tumor thrombotic microangiopathy is a rapidly progressive and fatal disease in which tumor cells embolize to the pulmonary microvasculature. This condition is characterized by severe dyspnea and right heart failure. Although pulmonary tumor thrombotic microangiopathy typically occurs in patients with untreated and/or advanced cancer, its occurrence in patients who are responding well to medical therapy is poorly documented.

Case presentation
A 68-year-old Japanese woman who had received four cycles of immuno-chemotherapy (pembrolizumab, carboplatin, and pemetrexed) followed by three cycles of maintenance therapy (pembrolizumab and pemetrexed) for advanced non-small cell lung cancer and had achieved a partial response with a stable clinical course was admitted to the emergency ward because of worsening breathlessness and general fatigue for 1 week. Chest computed tomography showed no evidence of tumor progression or any new lung lesion. Two-dimensional transthoracic echocardiography demonstrated right atrial and ventricular dilatation, tricuspid regurgitation, and a high trans-tricuspid pressure gradient of 65 mmHg. Despite her percutaneous oxygen saturation being 96% on room air at the time of admission, it worsened rapidly; the patient requiring 8 L/min of oxygen within 4 h. Repeat computed tomography with contrast medium revealed no evidence of pulmonary embolism. The patient developed progressive respiratory failure that was unresponsive to optimal cardio-pulmonary supportive therapy. An autopsy revealed tumorous clusters in pre-capillary lung vessels, whereas the primary lesion had shrunk to the point of almost complete resolution.

Conclusion
Pulmonary tumor thrombotic microangiopathy occurs not only in patients with advanced and/or uncontrolled cancer but also in those whose primary lesion seems to have been well controlled by medical treatment.
Heroin-induced osteoporosis presented with bilateral femoral neck insufficiency fractures in a male adult: a case report
Authors: Shih Yu-Jen , Chang Wei-Ning , Yang Shan-Wei 
Published: April 2023

Abstract
Background
Osteoporosis has been associated with several disorders; however, there have been only a limited number of reports on heroin-induced osteoporosis. We report a rare case presented with bilateral femoral neck insufficiency fractures without trauma history, caused by heroin-induced osteoporosis. We collect sufficient clinical data and further shed light on the potential mechanism of how heroin affects bone formation and decreases bone density.

Case presentation
A 55-year-old male patient with normal body mass index (BMI) suffered from bilateral hips pain gradually without trauma history. He had intravenous heroin addiction for more than 30 years. Radiography revealed bilateral femoral neck insufficiency fractures. Laboratory tests showed elevated alkaline phosphatase levels (365 U/L) and decreased inorganic phosphate (1.7 mg/dL), calcium (8.3 mg/dL), 25-(OH)D3 (20.3 ng/ml) and testosterone levels (2.12 ng/ml). Magnetic resonance imaging (MRI) revealed increased signals on STIR images over the sacral ala and bilateral proximal femur, and multiple band-like lesions at the vertebrae of the thoracic and lumbar spine. Bone densitometry revealed osteoporosis with a T score of minus 4.0. The screen for urine morphine was positive (> 1000 ng/ml). Through assessment of the patient, the diagnosis was insufficiency fractures of bilateral femoral neck caused by opioid-induced osteoporosis. After hemiarthroplasty, regular medication with vitamin D3 and calcium, and detoxification treatment, and the patient recovered well after 6 months of follow-up.

Conclusion
The aim of this report is to highlight the laboratory and radiology findings in a case of osteoporosis caused by opioid addiction and discuss the potential pathway by which osteoporosis is induced by opioids. When an unusual osteoporosis presents with insufficiency fractures, heroin-induced osteoporosis should be considered.
Biomechanical evaluation of reconstruction of the posterior complex in restorative laminoplasty with miniplates
Authors: Chen Jianmin , Liu Guoyin , Bao Tianyi , Xu Yuansheng , Luo Hu , Wu Yu , Cai Dawei , Qin Feng , Zhao Jianning 
Published: April 2023

Abstract
Objective
To evaluate the biomechanical effects of different miniplates on restorative laminoplasty.

Methods
Assembled restorative laminoplasty models were developed based on 3D printed L4 lamina. Based on different internal fixations, the research was divided into H-shaped miniplates (HSMs) group, two-hole miniplates (THMs) group, and L-shaped miniplates (LSMs) group. The static and dynamic compression tests were analyzed to investigate the biomechanical effects of different internal fixations in restorative laminoplasty, until the failure and fracture of miniplates, or the collapse of miniplates. The static compression tests adopted the speed control mode, and the dynamic fatigue compression tests adopted the load control mode.

Results
The “door close” and the collapse of lamina occurred in THMs group and LSMs group, and plate break occurred in LSMs group. However, these phenomenon was absent in HSMs group, and only plate crack around a screw and looseness of a screw tail cap were found in HSMs group. The sustainable yield load of HSMs group was greater than that of THMs group and LSMs group (P < 0.05). No significant difference in yielding-displacement was found between HSMs group and LSMs group (P > 0.05), while both were much less than that of THMs (P < 0.05). Moreover, the compressive stiffness and the axial displacement under the same mechanical load were arranged as follows: HSMs group > LSMs group > THMs group (P < 0.05). The results of dynamic compression test revealed that the peak load of HSMs group could reached 873 N and was 95% of the average yield load of the static compression, and was better than that in THMs group and LSMs group (P < 0.05). Besides, according to the fatigue life-peak load diagram, the ultimate load of HSMs group was more than twice that of THMs group or LSMs group.

Conclusions
The mechanical strength of H-shaped miniplates was superior to two-hole miniplates and L-shaped miniplates in maintaining spinal canal enlargement and spinal stability, and was more excellent in fatigue stability and ultimate load.
Comparison of the total and hidden blood loss in patients undergoing single-level open and unilateral biportal endoscopic transforaminal lumbar interbody fusion: a retrospective case control study
Authors: Peng Yu-Jian , Fan Zhi-Ying , Wang Qian-Liang , Dai Jun , Zhang Qian-Zhong-Yi , Cao Jun-Yin , Liu Xiao-Feng , Yan Jun 
Published: April 2023

Abstract
Purpose
This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF).

Methods
A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler’s formula was employed to estimate the patient’s blood volume (PBV), Gross’s formula to estimate TBL, and Sehat’s formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance.

Results
TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group.

Conclusions
Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.
Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis
Authors: Ali Sumera Aziz , Razzaq Shama , Aziz Savera , Allana Ahreen , Ali Arzina Aziz , Naeem Shahla , Khowaja Nayab , Ur Rehman Fazal 
Published: April 2023

Abstract
Background
Iron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although studies are undertaken to assess iron efficacy, some gaps and limitations in the existing literature need to be addressed. To fill the gaps, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the role of iron in reducing anemia among WRA in low-middle-income countries (LMICs).

Methods
A comprehensive search strategy was used to search Medline through PubMed, Embase, and Science Direct for RCTs published between 2000 and 2020. The primary outcome was the mean change in hemoglobin level. We used standardized mean differences and their respective 95% CI to estimate the pooled effect. We used I2 statistics and Egger’s test to assess heterogeneity and publication bias, respectively. This review was carried out in accordance with revised guidelines based on the Preferred Reporting Items for Systematic Review and Meta-analysis.

Results
The findings showed that iron therapy improved hemoglobin and ferritin levels, though the results varied across studies. An overall pooled effect estimate for the role of iron therapy in improving the hemoglobin levels among WRA was -0.71 (95% CI: -1.27 to -0.14) (p = 0.008). Likewise, the overall pooled effect estimate for the role of iron therapy in improving the ferritin levels among WRA was -0.76 (95% CI: -1.56 to 0.04) (p = 0.04). The heterogeneity (I2) across included studies was found to be statistically significant for studies assessing hemoglobin (Q = 746.93, I2 = 97.59%, p = 0.000) and ferritin level (Q = 659.95, I2 = 97.88%, p = 0.000).

Conclusion
Iron therapy in any form may reduce anemia’s burden and improve hemoglobin and ferritin levels, indicating improvement in iron-deficiency anemia. More evidence is required, however, to assess the morbidity associated with iron consumption, such as side effects, work performance, economic outcomes, mental health, and adherence to the intervention, with a particular focus on married but non-pregnant women planning a pregnancy in the near future.

Trial registration
Registered with PROSPERO and ID is CRD42020185033.
Evidence requirements of permanently listed digital health applications (DiGA) and their implementation in the German DiGA directory: an analysis
Authors: Mäder Melanie , Timpel Patrick , Schönfelder Tonio , Militzer-Horstmann Carsta , Scheibe Sandy , Heinrich Ria , Häckl Dennis 
Published: April 2023

Abstract
Background
With its digital health application (DiGA)-system, Germany is considered one of Europe's pioneers in the field of evidence-based digital health. Incorporating DiGA into standard medical care must be based on evidence-based success factors; however, a comprehensive overview of the evidence required of scientific studies for their approval is lacking.

Objective
The study aims to, (1) identify specific requirements defined by the Federal Institute for Drugs and Medical Devices (German: Bundesinstitut für Arzneimittel- und Medizinprodukte; BfArM) to design adequate studies, proving a positive healthcare effect, and (2) to assess the evidence given for applications permanently listed in the DiGA directory.

Methods
A multi-step approach was used: (1) identification of the evidence requirements for applications permanently listed in the DiGA directory, (2) identification of the evidence available supporting them.

Results
All DiGA permanently listed in the DiGA directory (13 applications) are included in the formal analysis. Most DiGA addressed mental health (n = 7), and can be prescribed for one or two indications (n = 10). All permanently listed DiGA have demonstrated their positive healthcare effect through a medical benefit, and most of them provide evidence for one defined primary endpoint. All DiGA manufacturers conducted a randomized controlled trial.

Discussion
It is striking that— although patient-relevant structural and procedural improvements show high potential for improving care, especially in terms of processes — all DiGA have provided a positive care effect via a medical benefit. Although BfArM accepts study designs with a lower level of evidence for the proof of a positive healthcare effect, all manufacturers conducted a study with a high level of evidence.

Conclusion
The results of this analysis indicate that permanently listed DiGA meet higher standards than required by the guideline.
Anatomical and biometric study of the mitral valve apparatus: application in valve repair surgery
Authors: Barry Misbaou , Gun Mesut , Hun-Chabry Yuthiline , Harmouche Majid , Peltier Johann , Caus Thierry , Havet Eric 
Published: April 2023

Abstract
Objective
Most mitral valve repair techniques provide excellent surgical results by removing regurgitation, but all of these techniques simultaneously reduce posterior valve mobility. A comprehensive biometric study of the mitral valve apparatus will provide landmarks that would help improve this posterior valve mobility.

Materials and methods
Thirty one (31) human hearts have been studied, from 14 women and 17 men. The characteristics of the studied sample were analyzed descriptively. The difference in means of the variables between women and men were tested using a Student t test. Correlations between the different measures were determined by simple regression analysis. Mean values are shown with ± 1 standard deviation and the limit of significance was set at 0.05.

Results
The mean weight of the hearts was 275.3 ± 2.4 g. The anteroposterior diameter of the mitral annulus was 29.3 ± 1.22 mm, the intertrigonal distance was 25.2 ± 3.50 mm and the anterior leaflet to posterior leaflet ratio was 1.9 ± 0.10, the length of the chordae A2 = 19.4 ± 1.15 mm and P2 = 14.5 ± 0.85 mm. The length of the anterior papillary muscle averaged 30.9 ± 7.20 mm and that of the posterior one 30.0 ± 8.75 mm. The comparison of the different values measured between women and men showed no statistically significant difference (p > 0.05). There was no correlation between these different measured values (p > 0.05).

Conclusion
A perfect knowledge of anatomy and biometry is therefore essential to offer alternative techniques that reproduce the real anatomy and physiology with a complete reconstruction of the mitral valve.
Berberine improves negative symptoms and cognitive function in patients with chronic schizophrenia via anti-inflammatory effect: a randomized clinical trial
Authors: Pu Zhengping , Wen Hui , Jiang Hongxia , Hou Qingmei , Yan Hui 
Published: April 2023

Abstract
Background
Based on the neuroinflammation hypothesis in schizophrenia and known anti-inflammatory effects of berberine, the aim of the present study is to investigate the efficacy of berberine in treating negative symptoms and cognitive deficits in adult patients with chronic schizophrenia.

Methods
Enrolled participants were randomized to receive berberine or placebo for 3 months. The Scale for the Assessment of Negative Symptoms (SANS), Trail-making Test A (TMT-A), Trail-making Test B (TMT-B), and Hopkins Verbal Learning Test (HVLT) were used to evaluate the negative symptoms and cognitive function at four-time points (baseline, 1st, 2nd, and 3rd month). Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were used as inflammatory markers. 106 patients with per-protocol were analyzed, 56 in the experimental (berberine) group and 50 in the control (placebo) group.

Results
From baseline to month 3, patients receiving berberine demonstrated a decrease in total scores on clinical scales SANS, TMT-A and TMT-B and showed a serum level reduction of IL-1β, IL-6 and TNF-α comparing with patients in the control group (P < 0.05). There were positive correlations between the change of serum IL-1β level and the change of SANS (r = 0.210, P = 0.039), TMT-A (r = 0.522, P < 0.001), and TMT-B (r = 0.811, P < 0.001); between the change of serum IL-6 level and the change of TMT-A (r = 0.562, P < 0.001), and TMT-B (r = 0.664, P < 0.001); between the change of serum TNF-α level and the change of TMT-B (r = 0.472, P < 0.001) after berberine treatment.

Conclusions
Berberine is an anti-inflammatory agent that can potentially mitigate the negative symptoms and cognitive deficits in patients with schizophrenia.
Automated classification of urine biomarkers to diagnose pancreatic cancer using 1-D convolutional neural networks
Authors: Karar Mohamed Esmail , El-Fishawy Nawal , Radad Marwa 
Published: April 2023

Abstract
Background
Early diagnosis of Pancreatic Ductal Adenocarcinoma (PDAC) is the main key to surviving cancer patients. Urine proteomic biomarkers which are creatinine, LYVE1, REG1B, and TFF1 present a promising non-invasive and inexpensive diagnostic method of the PDAC. Recent utilization of both microfluidics technology and artificial intelligence techniques enables accurate detection and analysis of these biomarkers. This paper proposes a new deep-learning model to identify urine biomarkers for the automated diagnosis of pancreatic cancers. The proposed model is composed of one-dimensional convolutional neural networks (1D-CNNs) and long short-term memory (LSTM). It can categorize patients into healthy pancreas, benign hepatobiliary disease, and PDAC cases automatically.

Results
Experiments and evaluations have been successfully done on a public dataset of 590 urine samples of three classes, which are 183 healthy pancreas samples, 208 benign hepatobiliary disease samples, and 199 PDAC samples. The results demonstrated that our proposed 1-D CNN + LSTM model achieved the best accuracy score of 97% and the area under curve (AUC) of 98% versus the state-of-the-art models to diagnose pancreatic cancers using urine biomarkers.

Conclusion
A new efficient 1D CNN-LSTM model has been successfully developed for early PDAC diagnosis using four proteomic urine biomarkers of creatinine, LYVE1, REG1B, and TFF1. This developed model showed superior performance on other machine learning classifiers in previous studies. The main prospect of this study is the laboratory realization of our proposed deep classifier on urinary biomarker panels for assisting diagnostic procedures of pancreatic cancer patients.