bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment across two decades of NIH-funded Alzheimer’s disease clinical trials
Authors: Ritchie Marina , Gillen Daniel L. , Grill Joshua D. 
Published: February 2023

Abstract
Background
Timely accrual of a representative sample is a key factor in whether Alzheimer’s disease (AD) clinical trials successfully answer the scientific questions under study. Studies in other fields have observed that, over time, recruitment to trials has become increasingly reliant on larger numbers of sites, with declines in the average per-site recruitment rate. Here, we examined the trends in recruitment over a 20-year period of NIH-funded AD clinical trials conducted by the Alzheimer’s Disease Cooperative Study (ADCS), a temporally consistent network of sites devoted to interventional research.

Methods
We performed retrospective analyses of eleven ADCS randomized clinical trials. To examine the recruitment planning, we calculated the expected number of participants to be enrolled per site for each trial. To examine the actual trial recruitment rates, we quantified the number of participants enrolled per site per month.

Results
No effects of time were observed on recruitment planning or overall recruitment rates across trials. No trial achieved an overall recruitment rate greater than one subject per site per month. We observed the fastest recruitment rates in trials with no competition and the slowest in trials that overlapped in time. The highest recruitment rates were consistently seen early within trials and declined over the course of studies.

Conclusions
Trial recruitment projections should plan for fewer than one participant randomized per site per month and consider the number of other AD trials being conducted concurrently.
Nanvuranlat, an L-type amino acid transporter (LAT1) inhibitor for patients with pretreated advanced refractory biliary tract cancer (BTC): Primary endpoint results of a randomized, double-blind, placebo-controlled phase 2 study.
Authors: Furuse Junji , Ikeda Masafumi , Ueno Makoto , Furukawa Masayuki , Morizane Chigusa , Takehara Tetsuo , Nishina Tomohiro , Todaka Akiko , Okano Naohiro , Hara Kazuo , Nakai Yousuke , Ohkawa Kazuyoshi , Sasaki Takashi , Sugimori Kazuya , Yokoyama Naoyuki , Yamamoto Kouji 
Published: February 2023

494 Background: LAT1 is a transporter ( SLC7A5) of L-type amino acid. Overexpression in cancer cells supports aggressive proliferation. High expression of LAT1 in tumor specimens has been identified as a predictor of poor prognosis in patients with various cancer types, including BTC. The efficacy and safety of nanvuranlat (JPH203), a first-in-class, single agent that selectively inhibits LAT1, was evaluated in patients with pretreated, advanced, refractory BTC in a placebo-controlled randomized trial. Methods: Patients with four different subtypes of advanced BTC were enrolled: intrahepatic (IHC), extrahepatic (EHC), gallbladder (GBC) and ampulla of Vater (AVC). All were refractory to or intolerant of standard chemotherapy and other investigational medicines. Patients were pre-classified as non-rapid acetylators via N-acetyltransferase 2 ( NAT2), to maximize efficacy/safety by minimizing the metabolism of nanvuranlat. The primary endpoint was progression-free survival (PFS), assessed by blinded independent center review (BICR), using RECIST 1.1. Results: At data cut-off (February 28, 2022), 211 BTC patients were consented at 14 centers in Japan. Using NAT2 testing for classification, a total of 106 patients were randomized (2:1) to nanvuranlat (n = 70) or placebo (n = 36). Nanvuranlat met its primary endpoint and demonstrated a statistically significant improvement in PFS by BICR in comparison with the placebo group (Hazard Ratio = 0.557; 95% CI, 0.3435 – 0.9029; one-sided p = 0.0164). The disease control rate (DCR) in the nanvuranlat group was approximately 25% (average = 24.6%) across all BTC subtypes, while it was 11.4% in the placebo group. Grade 3 adverse events were reported in 30.0% for nanvuranlat vs 22.9% for placebo. Treatment-related adverse event rates were respectively 41.4% and 57.1% in the nanvuranlat and placebo groups. No patient had adverse events leading to nanvuranlat treatment discontinuation, dose reduction, or death. Conclusions: The study met the primary endpoint. LAT1 inhibitor monotherapy with nanvuranlat demonstrated useful clinical efficacy in patients with four different subtypes of pre-treated, advanced, refractory BTC. Safe and highly tolerated profile was also documented. Clinical trial information: UMIN000034080 .
A Novel Cervical Vertebral Bone Quality Score Independently Predicts Cage Subsidence After Anterior Cervical Diskectomy and Fusion
Authors: Soliman Mohamed A. R. , Aguirre Alexander O. , Kuo Cathleen C. , Ruggiero Nicco , Khan Asham , Ghannam Moleca M. , Rho Kyungduk , Jowdy Patrick K. , Mullin Jeffrey P. , Pollina John 
Published: February 2023

BACKGROUND:
Surgeons can preoperatively assess bone quality using dual-energy X-ray absorptiometry or computed tomography; however, this is not feasible for all patients. Recently, a MRI-based scoring system was used to evaluate the lumbar spine's vertebral bone quality.

OBJECTIVE:
To create a similar MRI-based scoring system for the cervical spine (C-VBQ), correlate C-VBQ scores with computed tomography-Hounsfield units (HU), and evaluate the utility of this scoring system to independently predict cage subsidence after single-level anterior cervical diskectomy and fusion (ACDF).

METHODS:
Demographic, procedure-related, and radiographic data were collected for patients. Pearson correlation test was used to determine the correlation between C-VBQ and HU. Cage subsidence was defined as ≥3 mm loss of fusion segmental height. A multivariate logistic regression model was built to determine the correlation between potential risk factors for subsidence.

RESULTS:
Of 59 patients who underwent single-level ACDF, subsidence was found in 17 (28.8%). Mean C-VBQ scores were 2.22 ± 0.36 for no subsidence levels and 2.83 ± 0.38 (P < .001) for subsidence levels. On multivariate analysis, a higher C-VBQ score was significantly associated with subsidence (odds ratio = 1.85, 95% CI = 1.39-2.46, P < .001) and was the only significant independent predictor of subsidence after ACDF. There was a significant negative correlation between HU and C-VBQ (r2 = −0.49, P < .001).

CONCLUSION:
We found that a higher C-VBQ score was significantly associated with cage subsidence after ACDF. Furthermore, there was a significant negative correlation between C-VBQ and HU. The C-VBQ score may be a valuable tool for assessing preoperative bone quality and independently predicting cage subsidence after ACDF.
Leukocyte-Rich and Platelet-Rich Fibrin for Skull Base Reconstruction After Endoscopic Endonasal Skull Base Surgery
Authors: Constanzo Felipe , Pinto Jaime , Ledermann Cristian , Schmidt Thomas 
Published: February 2023

BACKGROUND:Postoperative cerebrospinal fluid (CSF) leak is one of the most common complications after endoscopic endonasal approach to the skull base.OBJECTIVE:To analyze the effect of leukocyte-rich and platelet-rich fibrin (L-PRF) as part of a standardized endonasal skull base repair protocol on postoperative infection and CSF leak rate.METHODS:One hundred three patients who underwent an endoscopic endonasal approach and were reconstructed using a standard technique (Group A) were compared with 139 patients using the same protocol with the addition of L-PRF (Group B). Postoperative intracranial infection and CSF leak at 6 months were analyzed.RESULTS:In patients with intraoperative CSF leak, postoperative leak occurred in 10.8% in Group A and 2.6% in Group B (P.024), and in patients with intraoperative high-flow leaks, the incidences were 11.7% and 3.1%, respectively (P.048). L-PRF reduced postoperative CSF leak by 76% in cases with intraoperative CSF leak (relative risk 0.24, 95% CI 0.06-0.87) and by 73% of patients with high-flow leak (relative risk 0.27, 95% CI 0.07-0.99). In patients undergoing surgery for diagnoses other than adenomas, there were no cases of postoperative leak in Group B, whereas in Group A occurred in 13.4% of those with intraoperative leaks (P.047) and 15.8% with high-flow intraoperative leaks (P.033). No significant differences were found in patients with pituitary adenoma. Meningitis occurred in 0.97% in Group A vs 2.16% in Group B (P.639), without differences between subgroups.CONCLUSION:L-PRF reduced the rate of postoperative CSF leaks in patients with intraoperative leaks, without differences on postoperative meningitis.
Ultra-low-dose CT is feasible for torsion measurement of the lower limb in patients with metal implants
Authors: Keller Gabriel , Grünwald Leonard , Springer Fabian 
Published: February 2023

Objectives: Patients who need torsion measurement of the lower limb often have metal implants hindering e.g. MRI. A new ultra-low-dose (ULD-)CT protocol might be feasible for torsion measurement at cost of relatively low radiation exposure. Methods: We retrospectively included all patients with clinically indicated torsion measurement in the period July 2019 to June 2021 and metal implants in the scanning field. The ULD-CT protocol comprised automated tube current time product and automated tube voltage with reference settings of 100kV/20mAs (hip), 80kV/20mAs (knee) and 80kV/10mAs (ankle). Femoral neck anteversion, tibial, intra-articular knee and overall leg torsion measurements were performed by two radiologists independently. Diagnostic confidence regarding the delineation of the relevant cortical bone was rated on a 5-point Likert scale (1 = non-diagnostic, 5 = excellent). Results: 102 consecutive patients could be included (BMI 27.38 ± 5.85) with 154 metal implants. Median total dose length product of the ULD-CT-torsion measurement was 16.5mGycm [11-39]. Both readers showed high agreement with a maximum torsional difference of 4.1°. Diagnostic confidence was rated best (5/5) in 92.2% (reader 1) and 93.1% (reader 2) with a worst rating of 3/5. Conclusion: The new ULD-CT protocol is feasible for torsion measurement of the lower limb – even in patients with metal implants. Advances in knowledge: Metal implants are not an obstacle for ULD-CT torsion measurements of the lower limb.
A METHOD FOR ASSESSMENT OF RESULTS OF SPECIALISED “DENTAL HEALTH LESSONS” IMPLEMENTATION AS AN EFFECTIVE TOOL FOR PREVENTION OF MOST COMMON DENTAL DISEASES IN CHILDREN WITH VISION PATHOLOGY
Authors: Surdo Elvira S. , Galonisky Vladislav G. 
Published: February 2023

The “dental health lessons” are an effective tool for prevention of dental diseases in healthy children and children with health limitations. This technology was developed for children with vision pathology. Therewith, objective assessment of its implementation from the standpoint of digestion of theoretical material and practical skills remains relevant.
Aim of study. To increase the efficacy of prevention of most common dental diseases in children with visual sensory deprivation based on development and practical implementation of objective control of qualitative characteristics related to the effectiveness of specialised “dental health lessons”.
Materials and methods. A method for objective control of practical implementation of remedial “dental health lessons” for children with vision pathology based on sociological research methods and on universal mathematical technologies for interpretation of the results obtained has been developed. The efficacy of practical implementation of the aforementioned method in specialised type III and IV pre-school educational institutions and schools in Krasnoyarsk has been evaluated.
Results and discussion. The results of practical implementation of the developed method revealed the sufficient quality of the assessment tools: questionnaires and check-lists for assessment of the knowledge and practical skills obtained accounting for the specifics of the general somatic and psychophysiological condition of the blind and vision-impaired children based on the pedagogy for blind and vision-impaired students adjusted for different age-related developmental stages. The method is highly informative, objective and reliable for diagnostics of the presence of relevant knowledge and skills in vision-impaired children and makes it possible to determine the necessity and the tactics of further remedial classes.
Conclusion. The method developed makes it possible to perform objective and reliable assessment of theoretical knowledge and practical skills related to dental disease prevention based on numerical evaluation. The method is non-invasive and harmless for the subjects, highly informative, simple in application, does not require expensive equipment and special training of the personnel, which provides the possibility of its application in pre-school educational institutions and schools without additional time expenditure by the dental practitioner.
DETERMINING CONSUMER APPEAL OF SELECTED GARDEN STRAWBERRY VARIETIES (FRAGARIA × ANANASSA DUCH.)
Authors: Luk’yanchuk Irina V. , Zhbanova Ekaterina V. , Lyzhin Alexander S. 
Published: February 2023

Improving the biochemical strawberry fruit composition and aroma is an important goal to develop the assortment of strawberry plants because only a few present-day varieties combine the high quality and aroma in strawberry fruits with increased accumulation of the biochemical composition components. The paper aims to assess hybrid strawberry seedlings based on a range of properties in strawberry fruits to select the most promising genotypes. Strawberry aroma and its consumer appeal were evaluated organoleptically. The biochemical component was tested in the laboratory according to standard methods, and the strawberry aroma was evaluated using DNA markers.
The research identified promising genotypes showing a high level of different characteristics: 75-30 (Tokado × Elianny) – consumer appeal (5.0 points), flavor (4.5 points), polychlorinated biphenyl levels [PCB] (9.2% Brix), and vitamin C (72.1 mg/100 g); 34-2 (922-67 × Privlekatelnaya) – consumer appeal (5.0 points), strawberry aroma (FaOMT gene), flavor (4.5 points), РСВ levels (14.7% Brix), and sugars (10.8%); 153-41 (Senga Sengana × Redcoat) –consumer appeal (5.0 points), strawberry aroma (FaOMT gene), PCB levels (12.8% Brix), sugars (10.2%), and vitamin C (76.1 mg/100 g); 153-60 (Senga Sengana × Redcoat) – consumer appeal (5.0 points), strawberry aroma (FaOMT gene), flavor (4.6 points), PCB levels (11.7% Brix), and sugars (10.5%); 35-16 (922-67 × Maryshka) – flavor (4.6 points) and anthocyanins levels (90.7 mg/100 g); 72-25 (Privlekatelnaya × Bylinnaya) – combination of FaOMT and FaFAD1 strawberry aroma genes.
FEATURES OF TEAM BUILDING AT AGRICULTURAL ENTERPRISES
Authors: Petrov Sergey V. 
Published: February 2023

Background. Team building is one of the most effective tools to improve the effectiveness of both human resources and the entire organization. For agricultural enterprises there is its own specifics of the implementation of team building activities, which is considered in this study.
Purpose. The goal is to study the experience of team building, taking into account the specifics of the agricultural industry and to identify the most common and significant trends associated with the development and implementation of teambuilding tools in enterprises of agricultural complex.
Materials and methods. Information from various publicly available sources, as well as the author’s own observations and conclusions in the process of analysis and development of the author’s methods on the subject of research. General scientific methods used are analysis, systematic approach and modeling; special scientific methods used are historical and logical methods.
Results. The following should be considered the most important results:
1. Key factors that have the greatest influence on the specifics of team building in agricultural organizations are described.
2. The main tendencies of agricultural development and some aspects of team building in agricultural enterprises are described.
3. Algorithm of implementation of team building in agricultural enterprises is developed and described.
Conclusion. The study and implementation of the world’s best practices in team building in the domestic agricultural enterprises will significantly increase the motivation of staff, which will increase the realization of the potential of human resources of the agricultural complex, the result will be the growth of efficiency of Russian agricultural enterprises. Further research should be carried out in the direction of each of the stages of the author’s algorithm of team building in agricultural enterprises.
Small animal Review
Authors: Gough Alex 
Published: February 2023

Summary: This issue's Small Animal Review features studies that seek to answer the long-standing question of the role of angiotensin-converting enzyme inhibitors in preclinical myxomatous mitral valve disease. Previous recommendations have suggested they are beneficial for use in dogs before they present with clinical signs, if cardiomegaly was present on radiographic or ultrasonographic examination. Systematic reviews and meta-analyses are considered the highest form of evidence and they can be helpful in answering questions when single trials do not have sufficient power to be conclusive.samples in measuring exposure to aromatic amines.
Factors associated with unskilled birth attendance among women in sub-Saharan Africa: A multivariate-geospatial analysis of demographic and health surveys
Authors: Addo Isaac Yeboah , Acquah Evelyn , Nyarko Samuel H. , Boateng Ebenezer N. K. , Dickson Kwamena Sekyi 
Published: February 2023

BackgroundSeveral studies have shown that unskilled birth attendance is associated with maternal and neonatal morbidity, disability, and death in sub-Saharan Africa (SSA). However, little evidence exists on prevailing geospatial variations and the factors underscoring the patterns of unskilled birth attendance in the region. This study analysed the geospatial disparities and factors associated with unskilled birth attendance in SSA.MethodsThe study is based on data from thirty (30) SSA countries captured in the latest (2010–2019) demographic and health surveys (DHS). A total of 200,736 women aged between 15–49 years were included in the study. Geospatial methods including spatial autocorrelation and hot spot analysis as well as logistic regression models were used to analyse the data.ResultsThere were random spatial variations in unskilled birth attendance in SSA, with the main hotspot located in Chad, whereas South Africa and the Democratic Republic of Congo showed coldspots. Residence (urban or rural), wealth status, education, maternal age at the time of the survey and age at birth, desire for birth, occupation, media exposure, distance to a health facility, antenatal care visits, and deaths of under-five children showed significant associations with unskilled birth attendance.ConclusionRandom geospatial disparities in unskilled birth attendance exist in SSA, coupled with various associated socio-demographic determinants. Specific geospatial hotspots of unskilled birth attendance in SSA can be targeted for specialised interventions to alleviate the prevailing disparities.
Micronutrients and cognitive functions among urban school-going children and adolescents: A cross-sectional multicentric study from India
Authors: Singh Shweta , Awasthi Shally , Kumar Divas , Sarraf Seema Rani , Pandey Anuj Kumar , Agarwal Girdhar G. , Awasthi Avivar , T. S. Anish , Mathew Joseph L. , Kar Sonali , Nair Suma , Rao Chythra R. , Pande Harsh , Mahanta B. N. , Bharti Bhavneet , Singh C. M. , Singh Kuldeep , Bhat Mushtaq A. , A. R. Somashekar , Awasthi Rajiv , Mahdi Abbas Ali 
Published: February 2023

Background
Micronutrient deficiency (MD) is associated with deficits in cognitive functioning of children. However, no comprehensive multicentric study has been conducted in India to explore the role of multiple MD in cognition of children and adolescents. The present study aimed to explore association of MD with level of general intelligence and specific cognitive functions, in urban school-going children and adolescents across ten cities of India.

Method
Cross-sectional multicentric study, enrolled participants aged 6–16 years. Blood samples were collected for biochemical analysis of calcium, iron, zinc, selenium, folate, vitamin A, D and B12. Colored Progressive Matrices / Standard Progressive Matrices (CPM/SPM), Coding, Digit Span and Arithmetic tests were used for the assessment of cognitive functions of participants. Height and weight measures were collected along with socio-economic status.

Results
From April-2019 to February-2020, 2428 participants were recruited from 60 schools. No MD was found in 7.0% (134/1918), any one MD in 23.8% (457/1918) and ≥ 2 MD in 69.2% (1327/1918) participants. In presence of ≥ 2 MD, adjusted odds ratio (OR) for borderline or dull normal in CPM/SPM was 1.63, (95% CI: 1.05–2.52), coding was 1.66 (95% CI: 1.02–2.71), digit span was 1.55 (95% CI: 1.06–2.25) and arithmetic was 1.72 (95% CI: 1.17–2.53), controlling for gender, socioeconomic status and anthropometric indicators.

Conclusion
Since ≥ 2 MD were found in more than 2/3rd of participants and was associated with impairment in cognitive function, attempts must be made to ameliorate them on priority in school going children in India.

Trial registration number
CTRI/2019/02/017783.
Lung deflation while placing a subclavian vein catheter: Our experience in minimizing the risk of pneumothorax
Authors: Rabadi Daher K. , Abubaker Ahmad K. , Almasarweh Sami A. 
Published: February 2023

Purpose
Lung deflation may reduce the risk of pneumothorax based on the assumption that the distance between the subclavian vein and the lung pleura would increase as well as the diameter of the vein. We aim to provide evidence to support the suggested desideratum of deflation in adults.

Methods
A prospective database was created that included patients who underwent subclavian vein catheterization for monitoring and therapeutic reasons from January 2014 to January 2020. Measurements using ultrasonography of the diameter of the subclavian vein were taken while the patient’s breathing was controlled by a ventilator and then repeated after disconnecting the mechanical ventilation and opening the pressure relief valve.

Results
A total of 123 patients were enrolled, with an average age of 41.9 years. The subclavian vein diameter was measured during controlled breathing with a mean average of 8.1 ± 0.6mm in males and 7.1 ± 0.5mm in females. The average increase after lung deflation with the pressure relief valve closed was 8.0± 5.1mm in males and 13.9 ± 5.4mm in females. An increase was noticed after opening a pressure valve, and the means were 5.5 ± 2.8mm in males and 5.1 ± 3.3mm in females. The catheter malposition rate was 0.8%

Conclusion
The benefit of interrupting mechanical ventilation and lung deflation lies within possibly avoiding pneumothorax as a complication of subclavian vein catheterization. These findings support the need for evidence regarding the curtailment of pneumothorax incidence in spontaneously breathing patients and the suggested increase in first-time punctures and success rates.