bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of low dose biotin supplements (<300μg/day) in the treatment of patients with hypothyroidism: crucial or overestimated?
Authors: Angelopoulos Nicholas , Paparodis Rodis D. , Androulakis Ioannis , Anagnostis Panagiotis , Boniakos Anastasios , Duntas Leonidas , Karras Spyridon N. , Livadas Sarantis 
Published: July 2023

Abstract
Background
In the last decade, the combination of the widespread use of streptavidin–biotin technology and biotin–containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 μg/day.

Methods
Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300μg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS.

Results
A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation.

Conclusion
Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don’t occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.
Interrogating colorectal cancer metastasis to liver: a search for clinically viable compounds and mechanistic insights in colorectal cancer Patient Derived Organoids
Authors: Cioce Mario , Fumagalli Maria Rita , Donzelli Sara , Goeman Frauke , Canu Valeria , Rutigliano Daniela , Orlandi Giulia , Sacconi Andrea , Pulito Claudio , Palcau Alina Catalina , Fanciulli Maurizio , Morrone Aldo , Diodoro Maria Grazia , Caricato Marco , Crescenzi Anna , Verri Martina , Fazio Vito Michele , Zapperi Stefano , Levrero Massimo , Strano Sabrina , Grazi Gian Luca , La Porta Caterina , Blandino Giovanni 
Published: July 2023

Abstract
Background
Approximately 20–50% of patients presenting with localized colorectal cancer progress to stage IV metastatic disease (mCRC) following initial treatment and this is a major prognostic determinant. Here, we have interrogated a heterogeneous set of primary colorectal cancer (CRC), liver CRC metastases and adjacent liver tissue to identify molecular determinants of the colon to liver spreading. Screening Food and Drug Administration (FDA) approved drugs for their ability to interfere with an identified colon to liver metastasis signature may help filling an unmet therapeutic need.

Methods
RNA sequencing of primary colorectal cancer specimens vs adjacent liver tissue vs synchronous and asynchronous liver metastases. Pathways enrichment analyses. The Library of Integrated Network-based Cellular Signatures (LINCS)-based and Connectivity Map (CMAP)-mediated identification of FDA-approved compounds capable to interfere with a 22 gene signature from primary CRC and liver metastases. Testing the identified compounds on CRC-Patient Derived Organoid (PDO) cultures. Microscopy and Fluorescence Activated Cell Sorting (FACS) based analysis of the treated PDOs.

Results
We have found that liver metastases acquire features of the adjacent liver tissue while partially losing those of the primary tumors they derived from. We have identified a 22-gene signature differentially expressed among primary tumors and metastases and validated in public databases. A pharmacogenomic screening for FDA-approved compounds capable of interfering with this signature has been performed. We have validated some of the identified representative compounds in CRC-Patient Derived Organoid cultures (PDOs) and found that pentoxyfilline and, to a minor extent, dexketoprofen and desloratadine, can variably interfere with number, size and viability of the CRC –PDOs in a patient-specific way. We explored the pentoxifylline mechanism of action and found that pentoxifylline treatment attenuated the 5-FU elicited increase of ALDHhigh cells by attenuating the IL-6 mediated STAT3 (tyr705) phosphorylation.

Conclusions
Pentoxifylline synergizes with 5-Fluorouracil (5-FU) in attenuating organoid formation. It does so by interfering with an IL-6-STAT3 axis leading to the emergence of chemoresistant ALDHhigh cell subpopulations in 5-FU treated PDOs. A larger cohort of CRC-PDOs will be required to validate and expand on the findings of this proof-of-concept study.
Using a multistep approach with multidisciplinary team to increase the diagnosis rate of Lynch syndrome-associated colorectal cancer after universal screening: a single-center study in Japan
Authors: Tatsuta Kyota , Sakata Mayu , Iwaizumi Moriya , Kojima Risa , Yamanaka Katsumasa , Baba Satoshi , Suzuki Katsunori , Morita Yoshifumi , Kikuchi Hirotoshi , Hiramatsu Yoshihiro , Kurachi Kiyotaka , Takeuchi Hiroya 
Published: July 2023

Abstract
Backgrounds
: This study aimed to evaluate the changes in the rates of genetic counseling and genetic testing as well as the diagnosis rate of Lynch syndrome (LS)-associated colorectal cancer before and after multistep approach with multidisciplinary team in Japanese.

Methods
In September 2016, we started universal screening for LS by mismatch repair protein immunohistochemistry and prospectively collected the records. Following patient interviews, we started multistep approach with multidisciplinary team (MA) in January 2020. MA consists of six surgeons, one genetic counselor, one medical geneticist, and six pathologists. MA is set up to compensate for patients’ lack of knowledge about genetic diseases and make case selection for elderly colorectal cancer patients with deficient mismatch repair (dMMR). MA is designed as a system that could be performed by a small number of medical genetic specialists. A total of 522 patients were included during the study duration, 323 and 199 patients in the pre-MA (P-MA) and MA groups, respectively.

Results
The frequency of dMMR in all patients was 10.0%. The patient interview results indicated a significant lack of patient education regarding genetic diseases. The rates of genetic counseling and genetic testing was significantly higher in MA group than in P-MA group (genetic counseling: MA 34.6% vs. P-MA 7.7%, p = 0.04; genetic testing: MA 30.8% vs. P-MA 3.8%, p = 0.02). Moreover, the diagnosis rate of LS-associated colorectal cancer was significantly higher in MA group (2.5%) than in P-MA group (0.3%) (P = 0.03). In addition, MA could be performed without problems despite the small number of medical and human genetics specialists.

Conclusions
MA has achieved appropriate pickup of suspected hereditary colorectal cancer patients and complemented the lack of knowledge about genetic diseases. The introduction of MA increased LS-associated colorectal cancer after universal screening. MA is an appropriate LS screening protocol for Japanese patients who lag behind in medical and human genetics education.
Comprehensive analysis of neoantigens derived from structural variation across whole genomes from 2528 tumors
Authors: Shi Yang , Jing Biyang , Xi Ruibin 
Published: July 2023

Abstract
Background
Neoantigens are critical for anti-tumor immunity and have been long-envisioned as promising therapeutic targets. However, current neoantigen analyses mostly focus on single nucleotide variations (SNVs) and indel mutations and seldom consider structural variations (SVs) that are also prevalent in cancer.

Results
Here, we develop a computational method termed NeoSV, which incorporates SV annotation, protein fragmentation, and MHC binding prediction together, to predict SV-derived neoantigens. Analysis of 2528 whole genomes reveals that SVs significantly contribute to the neoantigen repertoire in both quantity and quality. Whereas most neoantigens are patient-specific, shared neoantigens are identified with high occurrence rates in breast, ovarian, and gastrointestinal cancers. We observe extensive immunoediting on SV-derived neoantigens, especially on clonal events, which suggests their immunogenic potential. We also demonstrate that genomic alteration-related neoantigen burden, which integrates SV-derived neoantigens, depicts the tumor-immune interplay better than tumor neoantigen burden and may improve patient selection for immunotherapy.

Conclusions
Our study fills the gap in the current neoantigen repertoire and provides a valuable resource for cancer vaccine development.
Sensitive inference of alignment-safe intervals from biodiverse protein sequence clusters using EMERALD
Authors: Grigorjew Andreas , Gynter Artur , Dias Fernando H. C. , Buchfink Benjamin , Drost Hajk-Georg , Tomescu Alexandru I. 
Published: July 2023

﻿AbstractSequence alignments are the foundations of life science research, but most innovation so far focuses on optimal alignments, while information derived from suboptimal solutions is ignored. We argue that one optimal alignment per pairwise sequence comparison is a reasonable approximation when dealing with very similar sequences but is insufficient when exploring the biodiversity of the protein universe at tree-of-life scale. To overcome this limitation, we introduce pairwise alignment-safety to uncover the amino acid positions robustly shared across all suboptimal solutions. We implement EMERALD, a software library for alignment-safety inference, and apply it to 400k sequences from the SwissProt database.
MSV: a modular structural variant caller that reveals nested and complex rearrangements by unifying breakends inferred directly from reads
Authors: Schmidt Markus , Kutzner Arne 
Published: July 2023

AbstractStructural variant (SV) calling belongs to the standard tools of modern bioinformatics for identifying and describing alterations in genomes. Initially, this work presents several complex genomic rearrangements that reveal conceptual ambiguities inherent to the representation via basic SV. We contextualize these ambiguities theoretically as well as practically and propose a graph-based approach for resolving them. For various yeast genomes, we practically compute adjacency matrices of our graph model and demonstrate that they provide highly accurate descriptions of one genome in terms of another. An open-source prototype implementation of our approach is available under the MIT license at https://github.com/ITBE-Lab/MA.
The experience of device failure after cochlear implantation
Authors: Kim Jeong Heon , Choi Yeonjoo , Kang Woo Seok , Park Hong Ju , Ahn Joong Ho , Chung Jong Woo 
Published: July 2023

Background The present study describes the treatment of patients at a tertiary institution who experienced device failure after Cochlear Implantation (CI), as well as identifying prodromic symptoms that could assist in the timely identification and management of device failure. Study design Retrospective database review (January 2000–May 2017). Setting Single tertiary hospital. Methods Factors recorded included the etiology of hearing loss; age at first and revision CI surgeries; surgical information, including operation time and approach; electrical outcomes after implantation; device implanted; symptoms of device failure; history of head trauma; and audiologic outcomes as determined by categories of auditory performance (CAP). Results From January 2000 to May 2017, 1431 CIs were performed, with 27 (1.9%) undergoing revision surgeries due to device failure. The most common etiology of hearing loss was idiopathic (12/27), followed by cochlear hypoplasia (5/27). Mean age at initial CI was 11.8 (1–72) years, with 21 being pre-lingual and 6 being post-lingual. Of the total devices initially implanted, 80.5% were from Cochlear, 15.9% from MED-EL, and 3.5% from Advanced Bionics. The failure rates of these devices were 1.3%, 3.1%, and 10.0%, respectively. The most suggestive symptom of device failure was intermittent loss of signal. Mean CAP scores were 5.17 before reimplantation and 5.54 and 5.81 at 1- and 3-years, respectively, after reimplantation. Conclusion The most suggestive symptom preceding device failure was intermittent loss of signal. Patients who present with this symptom should undergo electrical examination for suspected device failure. Audiologic outcomes showed continuous development despite revision surgeries.
Impact of molar teeth distalization by clear aligners on temporomandibular joint: a three-dimensional study
Authors: Al-Tayar Barakat , Al-Somairi Majedh A. A. , ALshoaibi Lina H. , Wang Xiaoli , Wang Junbin , Liu Jiajie , Al-Tayar Baher , An Xiaoli , Si Qingzong 
Published: July 2023

Abstract
Background
Maxillary molar distalization is a common technique used in the non-extraction treatment of Angle Class II malocclusion that can effectively correct the molar relationship and create spaces for anterior teeth alignment. However, this approach may also impact the temporomandibular joint (TMJ) due to predictable changes in the posterior vertical dimension. Despite its widespread use, Class II malocclusions correction by molar distalization with clear aligners has not been investigated for their effects on the TMJ. Therefore, this study aimed to analyze the impact of sequential molar distalization using clear aligners on the TMJ.

Methods
Three-dimensional CBCT scans of 23 non-growing patients (7 males, 16 females; mean age 29.8 ± 4.6 years) with skeletal class I or II malocclusion and a bilateral molar class II relationship treated by sequential upper molars distalization with orthodontic clear aligners (Invisalign, Align Technology, San Josè, Ca, USA). A total of 46 joints were examined before and after molar distalization using Anatomage InvivoDental 6.0.3. Linear and angular measurements of the mandibular joint were measured, including joint parameters, inclination, position, and the dimension of the condyle and articular fossa. In addition, 3D volumetric spaces of the joint were analyzed. All data were statistically analyzed by paired T test to determine the differences between the pre-and post-orthodontic procedures.

Results
No statistically significant differences were found in all primary effects resulting from maxillary molars distalization by clear aligners on TMJ components measurements and joint spaces between T0 and T1. Meanwhile, statistically significant differences were observed in the linear position of the upper molars and the molar relationship parameter with at least P ≤ 0.05.

Conclusion
Treatment by sequential upper molars distalization with clear aligners does not lead to significant TMJ parameters changes in condyle and fossa spaces, dimensions, and positions.
Xylaria furcata reconsidered and nine resembling species
Authors: Ju Yu-Ming , Hsieh Huei-Mei , Suwannasai Nuttika 
Published: July 2023

Abstract
Background
Xylaria collections from termite nests with dichotomously branched stromata have been identified as X. furcata. However, Léveillé’s original material is no longer available, and the modern interpretation of X. furcata is based on a 1908 collection made by von Höhnel from termite nests at Buitenzorg Botanical Garden in Java. A packet of this von Höhnel material at FH was designated as the neotype by Rogers et al. in 2005.

Results
We reexamined the neotype from FH and its duplicates from various herbaria and found that three different species were mixed in these specimens. Despite that all of them have dichotomously branched stromata and tiny ascospores, only one fits the 2005 neotypification of X. furcata, where exposed perithecial mounds on the stromatal surface were unambiguously indicated. This portion of material is redesignated as the neotype, while the other two species with immersed perithecia are described as new: X. hoehnelii and X. robustifurcata. The ITS sequence obtained from the neotype helped us designate a specimen with cultures obtained from it as the epitype. From specimens identifiable as X. furcata, we describe four new species: X. brevifurcata, X. furcatula, X. insignifurcata, and X. tenellifurcata. Additionally, we recognize X. furcata var. hirsuta at the species level as X. hirsuta and consider X. scoparia a distinct species rather than a synonym of X. furcata. Molecular phylogenetic analyses based on three protein-coding loci showed that X. furcata and resembling species were grouped into two clusters: the X. furcata cluster with half-exposed to fully exposed perithecial mounds and the X. hoehnelii cluster with largely immersed perithecial mounds.

Conclusion
Ten species are recognized for X. furcata and resembling species, all of which could have been identified as X. furcata in the past. Its diversity has been overlooked primarily due to the small and similar stromata. Several additional species have been confirmed to be related to X. furcata by DNA sequences but are yet to be described due to the lack of mature stromata. While the species diversity of macrotermitine termites is equally high in Africa as in Asia, all of the species are primarily found in Asia, with X. hirsuta as the only exception. This suggests that there may be many more undiscovered species for this fungal group.
Management of potato brown rot disease using chemically synthesized CuO-NPs and MgO-NPs
Authors: Rabea Amira , Naeem E. , Balabel Naglaa M. , Daigham Ghadir E. 
Published: July 2023

Abstract
Background
Potatoes are a crucial vegetable crop in Egypt in terms of production and consumption. However, the potato industry suffers significant annual losses due to brown rot disease. This study aimed to suppress Ralstonia solanacearum (R. solanacearum), the causative agent of brown rot disease in potatoes, using efficient and economical medications such as CuO and MgO metal oxide nanoparticles, both in vitro and in vivo, to reduce the risk of pesticide residues.

Results
CuO and MgO metal oxide nanoparticles were synthesized via a simple chemical process. The average particle size, morphology, and structure of the nanoparticles were characterized using UV-visible spectroscopy, transmission electron microscopy (TEM), zeta potential analysis, X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. The growth of R. solanacearum was strongly inhibited by CuO and MgO NPs at a concentration of 3 mg/mL, resulting in zones of inhibition (ZOI) of 19.3 mm and 17 mm, respectively. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CuO-NPs and MgO-NPs were 0.5, 0.6, and 0.6, 0.75 mg/mL, respectively. When applied in vivo through seed dressing and tuber soaking at their respective MIC concentrations, CuO-NPs and MgO-NPs significantly reduced the incidence of brown rot disease to 71.2% and 69.4%, respectively, compared to 43.0% and 39.5% in bulk CuSO4 and bulk MgSO4 treatments, respectively. Furthermore, CuO-NPs and MgO-NPs significantly increased the yield, total chlorophyll content, and enzyme efficiency of potato plants compared with the infected control plants. TEM revealed that the bacterial cytomembrane was severely damaged by nanomechanical forces after interaction with CuO-NPs and MgO-NPs, as evidenced by lipid peroxidation and ultrastructural investigations.

Conclusion
The results of this study suggest that CuO-NPs and MgO-NPs can be used as intelligent agents to manage plant pathogens in agriculture. The use of metal oxide nanoparticles could provide a risk-free alternative for treating plant diseases, which are currently one of the biggest challenges faced by the potato industry in Egypt. The significant increase in yield, photosynthetic pigments, enzymatic activity, and total phenol-promoted resistance to R. solanacearum in potato plants treated with CuO-NPs and MgO-NPs compared to infected control plants highlights the potential benefits for the potato industry in Egypt. Further investigations are needed to explore using metal oxide nanoparticles for treating other plant diseases.
Development and characterization of a fecal-induced peritonitis model of murine sepsis: results from a multi-laboratory study and iterative modification of experimental conditions
Authors: Sharma Neha , Chwastek Damian , Dwivedi Dhruva J. , Schlechte Jared , Yu Ian-Ling , McDonald Braedon , Arora Jaskirat , Cani Erblin , Eng Mikaela , Engelberts Doreen , Kuhar Eva , Medeiros Sarah K. , Bourque Stephane L. , Cepinskas Gediminas , Gill Sean E. , Jahandideh Forough , Macala Kimberly F. , Panahi Sareh , Pape Cynthia , Sontag David , Sunohara-Neilson Janet , Fergusson Dean A. , Fox-Robichaud Alison E. , Liaw Patricia C. , Lalu Manoj M. , Mendelson Asher A. ,   for the National Preclinical Sepsis Platform, Sepsis Canada
Published: July 2023

Abstract
Background
Preclinical sepsis models have been criticized for their inability to recapitulate human sepsis and suffer from methodological shortcomings that limit external validity and reproducibility. The National Preclinical Sepsis Platform (NPSP) is a consortium of basic science researchers, veterinarians, and stakeholders in Canada undertaking standardized multi-laboratory sepsis research to increase the efficacy and efficiency of bench-to-bedside translation. In this study, we aimed to develop and characterize a 72-h fecal-induced peritonitis (FIP) model of murine sepsis conducted in two independent laboratories. The experimental protocol was optimized by sequentially modifying dose of fecal slurry and timing of antibiotics in an iterative fashion, and then repeating the experimental series at site 1 and site 2.

Results
Escalating doses of fecal slurry (0.5–2.5 mg/g) resulted in increased disease severity, as assessed by the modified Murine Sepsis Score (MSS). However, the MSS was poorly associated with progression to death during the experiments, and mice were found dead without elevated MSS scores. Administration of early antibiotics within 4 h of inoculation rescued the animals from sepsis compared with late administration of antibiotics after 12 h, as evidenced by 100% survival and reduced bacterial load in peritoneum and blood in the early antibiotic group. Site 1 and site 2 had statistically significant differences in mortality (60% vs 88%; p < 0.05) for the same dose of fecal slurry (0.75 mg/g) and marked differences in body temperature between groups.

Conclusions
We demonstrate a systematic approach to optimizing a 72-h FIP model of murine sepsis for use in multi-laboratory studies. Alterations to experimental conditions, such as dose of fecal slurry and timing of antibiotics, have clear impact on outcomes. Differences in mortality between sites despite rigorous standardization warrants further investigations to better understand inter-laboratory variation and methodological design in preclinical studies.