bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of haemorrhoids: rubber band ligation or sclerotherapy (THROS)? Study protocol for a multicentre, non-inferiority, randomised controlled trial
Authors: van Oostendorp J. Y. , Sluckin T. C. , Han-Geurts I. J. M. , van Dieren S. , Schouten R. ,   on behalf of the THROS trial research group
Published: June 2023

Abstract

Introduction
Haemorrhoidal disease (HD) is a common condition with significant epidemiologic and economic implications. While it is possible to treat symptomatic grade 1–2 haemorrhoids with rubber band ligation (RBL) or sclerotherapy (SCL), the effectiveness of these treatments compatible with current standards has not yet been investigated with a randomised controlled trial. The hypothesis is that SCL is not inferior to RBL in terms of symptom reduction (patient-related outcome measures (PROMs)), patient experience, complications or recurrence rate.

Methods and analysis
This protocol describes the methodology of a non-inferiority, multicentre, randomised controlled trial comparing rubber band ligation and sclerotherapy for symptomatic grade 1–2 haemorrhoids in adults (> 18 years). Patients are preferably randomised between the two treatment arms. However, patients with a strong preference for one of the treatments and refuse randomisation are eligible for the registration arm. Patients either receive 4 cc Aethoxysklerol 3% SCL or 3 × RBL. The primary outcome measures are symptom reduction by means of PROMs, recurrence and complication rates. Secondary outcome measures are patient experience, number of treatments and days of sick leave from work. Data are collected at 4 different time points.

Discussion
The THROS trial is the first large multicentre randomised trial to study the difference in effectivity between RBL and SCL for the treatment of grade 1–2 HD. It will provide information as to which treatment method (RBL or SCL) is the most effective, gives fewer complications and is experienced by the patient as the best option.

Ethics and dissemination
The study protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers, location AMC (nr. 2020_053). The gathered data and results will be submitted for publication in peer-reviewed journals and spread to coloproctological associations and guidelines.

Trial registration
Dutch Trial Register NL8377. Registered on 12–02-2020.
Cross-sectional analysis characterizing the use of rank preserving structural failure time in oncology studies: changes to hazard ratio and frequency of inappropriate use
Authors: Prasad Vinay , Kim Myung Sun , Haslam Alyson 
Published: June 2023

Abstract
Background
Rank preserving structural failure time (RPSFT) is a statistical method to correct or adjust for crossover in clinical trials, by estimating the counterfactual effect on overall survival (OS) when control arm patients do not receive the interventional drug when their tumor progresses. We sought to examine the strength of correlation between differences in uncorrected and corrected OS hazard ratios and percentage of crossover, and characterize instances of fundamental and sequential efficacy.

Methods
In a cross-sectional analysis (2003–2023), we reviewed oncology randomized trials that used RPSFT analysis to adjust the OS hazard ratio for patients who crossed over to an anti-cancer drug. We calculated the percentage of RPSFT studies evaluating a drug for fundamental efficacy (with or without a standard of care (SOC)) or sequential efficacy and the correlation between the OS hazard ratio difference (unadjusted and adjusted) and the percentage of crossover.

Results
Among 65 studies, the median difference between the uncorrected and corrected OS hazard ratio was −0.1 (quartile 1, quartile 3 : −0.3 to −0.06). The median percentage of crossover was 56% (quartile 1, quartile 3: 37% to 72%). All studies were funded by the industry or had authors who were employees of the industry. Twelve studies (19%) tested a drug’s fundamental efficacy when there was no SOC; 34 studies (52%) tested a drug’s fundamental efficacy when there was already a SOC; and 19 studies (29%) tested a drug’s sequential efficacy. The correlation between the uncorrected and corrected OS hazard ratio difference and the percentage of crossover was 0.44 (95% CI: 0.21 to 0.63).

Conclusions
RPSFT is a common tactic used by the industry to reinterpret trial results. Nineteen percent of RPSFT use is appropriate. We recognize that while crossover can bias OS results, the allowance and handling of crossover in trials should be limited to appropriate circumstances.
Production of short-chain fatty acids (SCFAs) as chemicals or substrates for microbes to obtain biochemicals
Authors: Tomás-Pejó Elia , González-Fernández Cristina , Greses Silvia , Kennes Christian , Otero-Logilde Nuria , Veiga María C. , Bolzonella David , Müller Bettina , Passoth Volkmar 
Published: June 2023

AbstractCarboxylic acids have become interesting platform molecules in the last years due to their versatility to act as carbon sources for different microorganisms or as precursors for the chemical industry. Among carboxylic acids, short-chain fatty acids (SCFAs) such as acetic, propionic, butyric, valeric, and caproic acids can be biotechnologically produced in an anaerobic fermentation process from lignocellulose or other organic wastes of agricultural, industrial, or municipal origin. The biosynthesis of SCFAs is advantageous compared to chemical synthesis, since the latter relies on fossil-derived raw materials, expensive and toxic catalysts and harsh process conditions. This review article gives an overview on biosynthesis of SCFAs from complex waste products. Different applications of SCFAs are explored and how these acids can be considered as a source of bioproducts, aiming at the development of a circular economy. The use of SCFAs as platform molecules requires adequate concentration and separation processes that are also addressed in this review. Various microorganisms such as bacteria or oleaginous yeasts can efficiently use SCFA mixtures derived from anaerobic fermentation, an attribute that can be exploited in microbial electrolytic cells or to produce biopolymers such as microbial oils or polyhydroxyalkanoates. Promising technologies for the microbial conversion of SCFAs into bioproducts are outlined with recent examples, highlighting SCFAs as interesting platform molecules for the development of future bioeconomy.
Plasma amyloid beta 42 is a biomarker for patients with hereditary, but not sporadic, cerebral amyloid angiopathy
Authors: de Kort Anna M. , Kuiperij H. Bea , Jäkel Lieke , Kersten Iris , Rasing Ingeborg , van Etten Ellis S. , van Rooden Sanneke , van Osch Matthias J. P. , Wermer Marieke J. H. , Terwindt Gisela M. , Schreuder Floris H. B. M. , Klijn Catharina J. M. , Verbeek Marcel M. 
Published: June 2023

Abstract
Background
The diagnosis of probable cerebral amyloid angiopathy (CAA) is currently mostly based on characteristics of brain MRI. Blood biomarkers would be a cost-effective, easily accessible diagnostic method that may complement diagnosis by MRI and aid in monitoring disease progression. We studied the diagnostic potential of plasma Aβ38, Aβ40, and Aβ42 in patients with hereditary Dutch-type CAA (D-CAA) and sporadic CAA (sCAA).

Methods
All Aβ peptides were quantified in the plasma by immunoassays in a discovery cohort (11 patients with presymptomatic D-CAA and 24 patients with symptomatic D-CAA, and 16 and 24 matched controls, respectively) and an independent validation cohort (54 patients with D-CAA, 26 presymptomatic and 28 symptomatic, and 39 and 46 matched controls, respectively). In addition, peptides were quantified in the plasma in a group of 61 patients with sCAA and 42 matched controls. We compared Aβ peptide levels between patients and controls using linear regression adjusting for age and sex.

Results
In the discovery cohort, we found significantly decreased levels of all Aβ peptides in patients with presymptomatic D-CAA (Aβ38: p < 0.001; Aβ40: p = 0.009; Aβ42: p < 0.001) and patients with symptomatic D-CAA (Aβ38: p < 0.001; Aβ40: p = 0.01; Aβ42: p < 0.001) compared with controls. In contrast, in the validation cohort, plasma Aβ38, Aβ40, and Aβ42 were similar in patients with presymptomatic D-CAA and controls (Aβ38: p = 0.18; Aβ40: p = 0.28; Aβ42: p = 0.63). In patients with symptomatic D-CAA and controls, plasma Aβ38 and Aβ40 were similar (Aβ38: p = 0.14; Aβ40: p = 0.38), whereas plasma Aβ42 was significantly decreased in patients with symptomatic D-CAA (p = 0.033). Plasma Aβ38, Aβ40, and Aβ42 levels were similar in patients with sCAA and controls (Aβ38: p = 0.092; Aβ40: p = 0.64. Aβ42: p = 0.68).

Conclusions
Plasma Aβ42 levels, but not plasma Aβ38 and Aβ40, may be used as a biomarker for patients with symptomatic D-CAA. In contrast, plasma Aβ38, Aβ40, and Aβ42 levels do not appear to be applicable as a biomarker in patients with sCAA.
Unilateral pulmonary vein atresia presenting with recurrent hemoptysis and bronchial varices in an Ethiopian adolescent: a case report
Authors: Weldetsadik Abate Yeshidinber , Kebede Abdi , Godu Binyam Gebremedhin , Gama Maru 
Published: June 2023

Abstract
Background
Congenital unilateral pulmonary vein atresia is a rare anomaly resulting from failure of the pulmonary vein to incorporate in the left atrium. It is a very rare cause of recurrent respiratory infections and hemoptysis requiring a high index of suspicion for proper diagnosis and management in early childhood.

Case presentation
We report a 13-year old Anuac (Ethiopia, Region of Gambela) male adolescent with a delayed diagnosis of isolated atresia of the left pulmonary veins despite early childhood presentation with recurrent chest infections, hemoptysis and exercise intolerance. Contrast enhanced CT of thorax with reconstructed planes confirmed the diagnosis. He underwent pneumonectomy for severe and recurrent symptoms and did well on subsequent follow ups after 6 months of pneumonectomy.

Conclusion
Although a rare anomaly, congenital unilateral pulmonary vein atresia should be considered in the differential diagnosis of a child presenting with recurrent chest infections, exercise intolerance and hemoptysis to facilitate early appropriate diagnosis and treatment.
Midterm outcome after en bloc resection of C2 chordoma with transoral mandibular split and mesh cage reconstruction: a case report
Authors: Korwutthikulrangsri Ekkapoj , Ongard Sunun , Pisutbenya Jirachai , Ruangchainikom Monchai , Sutipornpalangkul Werasak 
Published: June 2023

Abstract
Introduction
Chordomas are rare, locally aggressive tumors that often occur in the axial spine, especially in the sacrum. The treatment of chordomas located in the upper cervical spine is challenging. En bloc resection is the preferred surgical option for total tumor removal.

Case presentation
We report the case of a C2 chordoma in a 47-year-old Thai woman. She was treated with a two-stage, anterior–posterior, C2 total spondylectomy with titanium mesh cage reconstruction and radiotherapy. The first stage involved posterior stabilization from the occiput to C5, a total laminectomy, and removal of the posterior rings of the bilateral foramen transversarium to preserve the bilateral vertebral arteries. The second stage comprised a transoral mandibular split with en bloc resection of C2, followed by titanium mesh cage reconstruction and kick-off anterior cervical plating. At the 5 year follow-up, no tumor recurrence was identified on magnetic resonance imaging. The patient had no neurological deficits but still had minor complications from the anterior transoral mandibular split.

Conclusions
Excellent midterm results were obtained using a transoral mandibular split with reconstruction and posterior spinal fusion from the occiput to the lower cervical spine coupled with adjuvant radiotherapy. We recommend this approach as the treatment of choice for chordoma in the upper cervical spine.
Receiver architectures for positioning with low earth orbit satellite signals: a survey
Authors: Pinell Christina , Prol Fabricio S. , Bhuiyan M. Zahidul H. , Praks Jaan 
Published: June 2023

AbstractPositioning, Navigation and Timing (PNT) are services generally provided by Global Navigation Satellite Systems (GNSS). GNSS reside in medium to high orbital altitudes from the Earth’s surface, resulting in weak signal reception. However, user applications are increasingly in need of higher power signal strength or alternative PNT solutions. An influx of satellites in Low Earth Orbit (LEO) are driving such innovation in PNT technology. Improved signal strength compared to GNSS can be obtained from LEO satellites merely due to their proximity to Earth. Therefore, even communication satellite transmissions are becoming appealing to navigation, as so-called Signals of OPportunity (SOP). In order to benefit user applications, the receiver architectures for LEO-SOP, as well as potential LEO-PNT signals are explored.
Asymptotic results for a class of Markovian self-exciting processes
Authors: Seol Youngsoo 
Published: June 2023

AbstractHawkes process is a class of self-exciting point processes with clustering effect whose jump rate relies on their entire past history. This process is usually defined as a continuous-time setting and has been widely applied in several fields, including insurance, finance, queueing theory, and statistics. The Hawkes model is generally non-Markovian because the future development of a self-exciting point process is determined by the timing of past events. However, it can be Markovian in special cases such as when the exciting function is an exponential function or a sum of exponential functions. Difficulty arises when the exciting function is not an exponential function or a sum of exponentials, in which case the process can be non-Markovian. The inverse Markovian case for Hawkes processes was introduced by Seol (Stat. Probab. Lett. 155:108580, 2019) who studied some asymptotic behaviors. An extended version of the inverse Markovian Hawkes process was also studied by Seol (J. Korean Math. Soc. 58(4):819–833, 2021). In the current work, we propose a class of Markovian self-exciting processes that interpolates between the Hawkes process and the inverse Hawkes process. We derived limit theorems for the newly considered class of Markovian self-exciting processes. In particular, we established both the law of large numbers (LLN) and central limit theorems (CLT) with some key results.
In vitro repress of breast cancer by bio-product of edible Pleurotus ostreatus loaded with chitosan nanoparticles
Authors: Al-Rajhi Aisha M. H. , Ghany Tarek M. Abdel 
Published: June 2023

AbstractDespite advances in early detection and therapy, cancer still is a significant health challenge with the highest priority for investigation. Breast cancer represents the most common cancerous disease among women in the world. The study’s purpose is to estimate the cytotoxic activity of the edible mushroom Pleurotus ostreatus extract (PE), chitosan nanoparticles (ChNPs), and PE loaded with ChNPs (PELChNPs), as well as to identify the molecular docking of the cytotoxicity of methyl gallate (MG) as a main component of the PE against breast cancer (MCF-7) cell line. High-performance liquid chromatography (HPLC) analysis of PE exhibited the existence of various phenolic and flavonoid compounds such as MG, gallic acid, chlorogenic acid, hesperetin, naringenin, rutin, and cinnamic acid. The proliferation of the MCF-7 cell line was inhibited at 1, 3.9, and 62.50 µg/mL of PELChNPs, PE, and ChNPs, respectively. PELChNPs were more effective against the MCF-7 cell line than PE, particularly at low concentrations. For instance, at 7.8 µg/mL of PELChNPs and PE, the inhibitory % of MCF-7 proliferation was 20.59±1.75% and 8.57±0.59%, respectively. At 15.6 µg/mL of PELChNPs and PE, the inhibitory % of MCF-7 proliferation was 51.37±1.09% and 25.18±1.64%, respectively. While there is slight difference in the inhibition % of MCF-7 cells (98.64±0.21 and 97.22±0.16%) at high concentration 500 µg/mL of PELChNPs and PE, respectively. IC50 was 15.25 ± 0.54 µg/mL, 46.27 ± 1.94 µg/mL, and 337.38 ± 13.68 µg/mL against MCF-7 cell line of PELChNPs, PE, and ChNPs, respectively. The value of IC50 documented the efficacy of PELChNPs compared with the IC50 (5.91 ± 0.43 µg/mL) of Vinblastine sulfate. Noticeable distortions were observed in the MCF-7 cell line mainly treated with PELChNPs, followed by PE alone. While ChNPs exhibited less effect on the morphology of the MCF-7 cell line. Antioxidant activity of ChNPs, PE, and PELChNPs was evaluated compared with Trolox, which reflected IC50 = 118.33 ± 4.02, 85.63 ± 3.96, 36.80 ± 2.52 and 24.74 ± 0.45 µg/mL. Methyl gallate binding interactions were assessed using molecular docking with the MOE-Dock tool against the target crystal structures of Breast cancer cell line 3HB5. The results shed light on how molecular modeling techniques can inhibit methyl gallate with possible uses in treating breast cancer.
A bibliographic review of climate change and fertilization as the main drivers of maize yield: implications for food security
Authors: Ocwa Akasairi , Harsanyi Endre , Széles Adrienn , Holb Imre János , Szabó Szilárd , Rátonyi Tamás , Mohammed Safwan 
Published: June 2023

Abstract
Introduction
Crop production contribution to food security faces unprecedented challenge of increasing human population. This is due to the decline in major cereal crop yields including maize resulting from climate change and declining soil infertility. Changes in soil nutrient status and climate have continued to occur and in response, new fertilizer recommendations in terms of formulations and application rates are continuously developed and applied globally. In this sense, this review was conducted to: (i) identify the key areas of concentration of research on fertilizer and climate change effect on maize grain yield, (ii) assess the extent of the effect of climate change on maize grain yield, (iii) evaluate the extent of the effect of fertilization practices on maize grain yield, and (iv) examine the effect of interaction between climate change factors and fertilization practices on maize grain yield at global perspective.

Methodology
Comprehensive search of global literature was conducted in Web of Science (WoS) database. For objective 1, metadata on co-authorship (country, organisation), and co-occurrence of keywords were exported and analysed using VOSviewer software. For objective 2–4, yield data for each treatment presented in the articles were extracted and yield increment calculated.

Results
The most significant keywords: soil fertility, nutrient use efficiency, nitrogen use efficiency, integrated nutrient management, sustainability, and climate change adaptation revealed efforts to improve maize production, achieve food security, and protect the environment. A temperature rise of 1–4 °C decreased yield by 5–14% in warm areas and increased by < 5% in cold areas globally. Precipitation reduction decreased yield by 25–32%, while CO2 concentration increased and decreased yield by 2.4 to 7.3% and  9 to 14.6%, respectively. A promising fertilizer was a combination of urea + nitrapyrin with an average yield of 5.1 and 14.4 t ha−1 under non-irrigation and irrigation, respectively. Fertilization under climate change was projected to reduce yield in the average range of 10.5–18.3% by 2099.

Conclusion
The results signified that sole fertilizer intensification is insufficient to attain sustainable maize yield. Therefore, there is need for integrated agronomic research that combines fertilizers and other technologies for enhancing maize yield, and consequently maize contribution to the attainment of global food security under climate change conditions.
Long-read genome sequencing identifies cryptic structural variants in congenital aniridia cases
Authors: Damián Alejandra , Núñez-Moreno Gonzalo , Jubin Claire , Tamayo Alejandra , de Alba Marta Rodríguez , Villaverde Cristina , Fund Cédric , Delépine Marc , Leduc Aurélie , Deleuze Jean François , Mínguez Pablo , Ayuso Carmen , Corton Marta 
Published: June 2023

Abstract
Background
Haploinsufficiency of the transcription factor PAX6 is the main cause of congenital aniridia, a genetic disorder characterized by iris and foveal hypoplasia. 11p13 microdeletions altering PAX6 or its downstream regulatory region (DRR) are present in about 25% of patients; however, only a few complex rearrangements have been described to date. Here, we performed nanopore-based whole-genome sequencing to assess the presence of cryptic structural variants (SVs) on the only two unsolved “PAX6-negative” cases from a cohort of 110 patients with congenital aniridia after unsuccessfully short-read sequencing approaches.

Results
Long-read sequencing (LRS) unveiled balanced chromosomal rearrangements affecting the PAX6 locus at 11p13 in these two patients and allowed nucleotide-level breakpoint analysis. First, we identified a cryptic 4.9 Mb de novo inversion disrupting intron 7 of PAX6, further verified by targeted polymerase chain reaction amplification and sequencing and FISH-based cytogenetic analysis. Furthermore, LRS was decisive in correctly mapping a t(6;11) balanced translocation cytogenetically detected in a second proband with congenital aniridia and considered non-causal 15 years ago. LRS resolved that the breakpoint on chromosome 11 was indeed located at 11p13, disrupting the DNase I hypersensitive site 2 enhancer within the DRR of PAX6, 161 Kb from the causal gene. Patient-derived RNA expression analysis demonstrated PAX6 haploinsufficiency, thus supporting that the 11p13 breakpoint led to a positional effect by cleaving crucial enhancers for PAX6 transactivation. LRS analysis was also critical for mapping the exact breakpoint on chromosome 6 to the highly repetitive centromeric region at 6p11.1.

Conclusions
In both cases, the LRS-based identified SVs have been deemed the hidden pathogenic cause of congenital aniridia. Our study underscores the limitations of traditional short-read sequencing in uncovering pathogenic SVs affecting low-complexity regions of the genome and the value of LRS in providing insight into hidden sources of variation in rare genetic diseases.