bluuebunny/crossref_metadata_2025_split huggingface dataset:
A promising future for endometriosis diagnosis and therapy: extracellular vesicles - a systematic review
Authors: Scheck Simon , Paterson Emily S. J. , Henry Claire E. 
Published: December 2022

Abstract
Endometriosis is a chronic, inflammatory gynaecological disease that can have severe negative impacts on quality of life and fertility, placing burden on patients and the healthcare system. Due to the heterogeneous nature of endometriosis, and the lack of correlation between symptom and surgical disease severity, diagnosis and treatment remain a significant clinical challenge. Extracellular vesicles (EVs) are biologically active particles containing molecular cargo involved in intercellular communication, that can be exploited for diagnostic and therapeutic purposes.We systematically reviewed studies exploring EVs and their role in endometriosis, specifically addressing diagnostic and therapeutic potential and current understanding of pathophysiology. Five databases (Pubmed, Embase, Medline, Web of Science, Google Scholar) were searched for keywords ‘endometriosis’ and either ‘extracellular vesicles’ or ‘exosomes’.There were 28 studies included in the review. Endometrium derived EVs contribute to the development of endometriosis. EVs derived from endometriosis lesions contribute to angiogenesis, immunomodulation and fibrosis. Such EVs can be detected in blood, with early data demonstrating utility in diagnosis and recurrence detection. EV isolation techniques varied between studies and only eight of twenty-eight studies fully characterised EVs according to current recommended standards. Reporting/type of endometriosis was limited across studies. Varied patient population, type of sample and isolation techniques created bias and difficulty in comparing studies.EVs hold promise for improving care for symptomatic patients who have never had surgery, as well as those with recurrent symptoms after previous surgery. We encourage further EV research in endometriosis with the inclusion of rigorous reporting of both the patient population and technical methodology used, with the ultimate goal of achieving clinical utility for diagnosis, prognosis and eventually treatment.
A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management
Authors: Bradbury Melissa , Borràs Eva , Vilar Marta , Castellví Josep , Sánchez-Iglesias José Luis , Pérez-Benavente Assumpció , Gil-Moreno Antonio , Santamaria Anna , Sabidó Eduard 
Published: December 2022

Abstract
Background
High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR).

Methods
A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves.

Results
Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients’ age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72–0.92).

Conclusions
We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients’ care.
Diversity of human astroviruses in Germany 2018 and 2019
Authors: Niendorf Sandra , Mas Marques Andreas , Bock Claus-Thomas , Jacobsen Sonja 
Published: December 2022

AbstractAim of this study was to investigate the molecular diversity of human astroviruses (HAstV) in Germany. A follow-up study was performed with human stool samples collected in 2018–2019, which were genotyped retrospectively. A total of 2645 stool samples, collected between January 2018 and December 2019 from sporadic cases and outbreaks of acute gastroenteritis were analyzed. An algorithm of PCR systems was used to characterize human astrovirus. Human astroviruses were found in 40 samples (positive rate: 1.6%). During the study period, children aged 1–2 years (48%) were most affected by HAstV. Genotyping revealed a number of nine circulating genotypes representing four human Mamastrovirus species. Strain MLB1 was predominant in the study population with a detection rate of 25% followed by HAstV1 with a positive rate of 20%. The diversity of astrovirus genotypes seems to be rather stable in Germany in the last years. A clustering of regionally and/or temporally linked human astroviruses in Germany was not detectable.
Choosing the appropriate pharmacotherapy for nonspecific chronic low back pain
Authors: Migliorini Filippo , Maffulli Nicola 
Published: December 2022

AbstractThe pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore daily activities and improve the quality of life. No magic bullet exists for NCLBP; interventions to reduce pain and disability are available, but long-term results are unpredictable. Education in this regard needs to improve. This is often hard to accept for clinicians and patients, and provides a fertile soil to quacks, faith healers, and gurus to promote miraculous non-evidence-based solutions. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from a dedicated therapy. In this editorial, we provide an evidenced-based overview of the principles of pharmacological management of NCLPB.
A case report of robotic-assisted resection of large fibrous benign tumor of second rib
Authors: Liu Bohao , Gao Shan , Wu Qifei , Li Haijun , Zhang Guangjian , Fu Junke 
Published: December 2022

Abstract
Background
Surgical resection is the most effective curative management of benign rib tumors and carries an excellent prognosis. Due to complex anatomy and narrow field, higher rib resection is technically demanding and requires extensive dissection.

Case presentation
We report a case of second rib tumor resection performed transthoracic under Da Vinci robot assistance. A 32-year-old male complained about increasing pain in the left anterior chest wall. After 3D reconstruction of CT, it showed a well-circumscribed fusiform lesion with a multi-component structure. Measured 17 × 6 × 4 cm and extended into the chest cavity to the depth below the pectoralis minor muscle. The patient underwent robotic-assisted trans-thoracic second rib resection. At four weeks of outpatient follow-up, the patient reported no pain and uncomplicated wound healing.

Conclusion
This minimally invasive approach offers optimal visualization and tissue manipulation while dramatically decreasing the possibility of collateral damage, hence ensuring fast function recovery. To the best of our knowledge, these kinds of procedures are rarely reported in detail.
Prenatal diagnosis and molecular cytogenetic analyses of a paternal inherited deletion of 1q23.3 encompassing PBX1 gene
Authors: Luo Man , Gu Xia , Zhou Ting , Chen Chaoli 
Published: December 2022

Abstract
Background
Patients with deletions involving the long arm of chromosome 1 are rare. The PBX1 gene is located on chromosome 1q23.3. PBX1 encodes a transcription factor which promotes protein–protein interaction and plays a crucial role in several developmental processes. PBX1 haploinsufficiency had been reported to lead syndromic congenital anomalies of kidney and urinary tract (CAKUT) in humans.

Case presentation
In this research, a 24-year-old woman (gravida 1, para 0) underwent amniocentesis at 22 weeks’ gestation because of a horseshoe kidney of the fetus on prenatal ultrasound.

Results
Chromosomal microarray analysis (CMA) from this family revealed a 1.14 Mb paternal inherited deletion on chromosome 1q23.3, spanning from position 163,620,000 to 164,760,000 (hg19). Trio whole-exome sequencing (WES) showed heterozygous deletions in exons 1–2 of the PBX1 in fetal and paternal samples. At the 3-year follow-up, the baby did not have an abnormal phenotype except a horseshoe kidney.

Conclusion
We provide a detailed description of the phenotype in a family with paternal inherited deletion of 1q23.3 encompassing exons 1–2 of the PBX1 gene. Combination of karyotype analysis, CMA, WES, prenatal ultrasound and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.
The effect of targeted rheumatoid arthritis therapeutics on systemic inflammation and anemia: analysis of data from the CorEvitas RA registry
Authors: Padula Anthony S. , Pappas Dimitrios A. , Fiore Stefano , Blachley Taylor S. , Ford Kerri , Emeanuru Kelechi , Kremer Joel M. 
Published: December 2022

Abstract
Background
To evaluate the effects of tumor necrosis factor inhibitors (TNFi), interleukin-6 receptor inhibitors (IL-6Ri), and Janus kinase inhibitors (JAKi) on hemoglobin (Hb) and C-reactive protein (CRP) levels in adults enrolled in CorEvitas (formerly Corrona), a large US rheumatoid arthritis (RA) registry.

Methods
Patients who initiated TNFi, IL-6Ri, or JAKi treatment during or after January 2010, had Hb and CRP measurements at baseline and 6-month follow-up (± 3 months) and had continued therapy at least until that follow-up, through March 2020, were included in the analysis. Changes in Hb and CRP were assessed at month 6. Abnormal Hb was defined as < 12 g/dL (women) or < 13 g/dL (men); abnormal CRP was ≥ 0.8 mg/dL. Differences in Hb and CRP levels were evaluated using multivariable regression.

Results
Of 2772 patients (TNFi, 65%; IL-6Ri, 17%; JAKi, 17%) evaluated, 1044 (38%) had abnormal Hb or CRP at initiation; an additional 252 (9%) had both abnormal Hb and CRP. At month 6, the IL-6Ri group had a greater Hb increase than the TNFi (mean difference in effect on Hb: 0.28 g/dL; 95% CI 0.19–0.38) and JAKi (mean difference in effect on Hb: 0.47 g/dL; 95% CI 0.35–0.58) groups, regardless of baseline Hb status (both p < 0.001). The CRP decrease at month 6 was greater with IL-6Ri compared with TNFi and JAKi, regardless of baseline CRP status (both p < 0.05).

Conclusion
These real-world results align with the mechanism of IL-6R inhibition and may inform treatment decisions for patients with RA.
Lecanemab in patients with early Alzheimer’s disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study
Authors: McDade Eric , Cummings Jeffrey L. , Dhadda Shobha , Swanson Chad J. , Reyderman Larisa , Kanekiyo Michio , Koyama Akihiko , Irizarry Michael , Kramer Lynn D. , Bateman Randall J. 
Published: December 2022

Abstract
Background
Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab.

Methods
The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly for up to 24 months, with an intervening off-treatment period (gap period) ranging from 9 to 59 months (mean 24 months).

Results
At 12 and 18 months of treatment in the core, lecanemab 10 mg/kg biweekly demonstrated dose-dependent reductions of brain amyloid measured PET and corresponding changes in plasma biomarkers and slowing of cognitive decline. The rates of clinical progression during the gap were similar in lecanemab and placebo subjects, with clinical treatment differences maintained after discontinued dosing over an average of 24 months in the gap period. During the gap, plasma Aβ42/40 ratio and p-tau181 levels began to return towards pre-randomization levels more quickly than amyloid PET. At OLE baseline, treatment differences vs placebo at 18 months in the randomized period were maintained across 3 clinical assessments. In the OLE, lecanemab 10 mg/kg biweekly treatment produced dose-dependent reductions in amyloid PET SUVr, improvements in plasma Aβ42/40 ratio, and reductions in plasma p-tau181.

Conclusions
Lecanemab treatment resulted in significant reduction in amyloid plaques and a slowing of clinical decline. Data indicate that rapid and pronounced amyloid reduction correlates with clinical benefit and potential disease-modifying effects, as well as the potential to use plasma biomarkers to monitor for lecanemab treatment effects.

Trial registration
ClinicalTrials.gov NCT01767311.
Discovery and mechanism studies of a novel ATG4B inhibitor Ebselen by drug repurposing and its anti-colorectal cancer effects in mice
Authors: Xie Huazhong , Qiang Pengfei , Wang Yao , Xia Fan , Liu Peiqing , Li Min 
Published: December 2022

AbstractCysteine protease ATG4B, a key autophagy protein, is an attractive target for colorectal cancer therapy. However, ATG4B inhibitors with higher efficiency, safety, and clear mechanism are still limited. In this study, we discovered ATG4B inhibitors based on the FDA-approved drug library through FRET-based high-throughput screening and gel-based analysis. Among the nine hits, compound Ebselen showed the most potent ATG4B inhibitory activity (IC50 = 189 nM) and exhibited controllable selectivity and structural optimizable possibility against ATG4A and caspases. We then performed mass spectrometry assay and cysteine mutations to confirm that Ebselen could covalently bind to ATG4B at Cys74. Moreover, Cys292 and Cys361 instead of Cys74 are responsible for the redox-oligomerization and efficient activity inhibition of ATG4B. Ultimately through cell culture and mouse xenograft tumor models, we established the impact of Ebselen on autophagy and tumor suppression via ATG4B inhibition other than apoptosis. These results suggest that old drug Ebselen as an ATG4B inhibitor through oxidative modification may be repurposed as a promising anti-colorectal cancer drug.
The prognostic effect of ST-elevation in lead aVR on coronary artery disease, and outcome in acute coronary syndrome patients: a systematic review and meta-analysis
Authors: Kazemi Erfan , Mansoursamaei Ali , Bijan Morteza , Hosseinzadeh Ali , Sheibani Hossein 
Published: December 2022

Abstract
Background
Rapid diagnosis of coronary artery disease has an important role in saving patients. The aim of this study is to evaluate if aVR lead ST-elevation (STE) can predict LM/3VD, left main (LM) disease, and three-vessel disease (3VD), outcome in acute coronary syndrome (ACS) patients.

Methods
In this systematic review and meta-analysis, 45 qualified studies were entered. Scopus, Pub med, Google scholar, Web of science, Cochrane library were searched on 12 November 2021.

Results
This systematic review includes 52,175 participants. In patients with STE, the total odds ratios for LM, 3VD, and LM/3VD were 5.48 (95% CI 3.88, 7.76), 2.21 (95% CI 1.78, 3.27), and 6.21 (95% CI 3.49, 11,6), respectively. STE in lead aVR was linked with in-hospital death (OR = 2.99, CI 1.90, 4.72) and 90-day mortality (OR = 3.09, CI 2.17, 4.39), despite the fact that it could not predict 30-day mortality (OR = 1.11, CI 0.95, 1.31). The STE > 1 mm subgroup had the highest sensitivity for LM (0.9, 95% CI 0.82, 0.98), whereas the STE > 0.5 mm (0.76, 95% CI 0.61, 0.90) subgroup had the highest sensitivity for LM/3VD. The appropriate cut-off point with highest specificity for LM/3VD and LM was STE > 1.5 mm (0.80, 95% CI 0.75, 0.85) and STE > 0.5 mm, respectively (0.75, 95% CI 0.67, 0.84, I2 = 97%).

Conclusion
The odds of LM and LM/3VD were higher than 3VD in ACS patients with STE in lead aVR. Also, STE > 0.5 mm was the best cut-off point to screen LM/3VD, whereas for LM diagnosis, STE > 1 mm had the highest sensitivity. Furthermore, LM/3VD had a higher overall specificity than LM.
A high detail UAS-based 3D model of the Torre Benzalá in Jaén, Spain
Authors: Lerma-Cobo F. , Romero-Manchado A. , Enríquez C. , Ramos M. I. 
Published: December 2022

Abstract
The constant development of geomatics tools has driven the opening of their applications to multiple disciplines, including archaeology. The possibility of performing a 3D reconstruction of archaeological remains as well as a semantic classification of the 3D surface facilitates not only a better knowledge of the historical heritage but also an essential aid to the planning and development of restoration and preservation projects of this legacy. Different data exploitation strategies are needed to take advantage of the geospatial data provided by geomatics tools. In this paper, we have studied the current state of conservation of a medieval tower, Torre Benzalá in Jaén, southern Spain. The interesting thing about this study is that very high resolution RGB images, taken by a drone, have been used in order to show the current degree of deterioration of the tower, providing accurate and precise documentation of the current state. Thus, a highly detailed 3D reconstruction of the tower has been carried out. A dense point cloud was generated to obtain a digital elevation model (DEM) to identify and quantify the most critically deteriorated areas. The results are useful for the development of an architectural maintenance and restoration project to preserve this archaeological legacy.
Spectroscopic analysis of mushrooms by surface-enhanced Raman scattering (SERS)
Authors: Puliga Federico , Zuffi Veronica , Zambonelli Alessandra , Francioso Ornella , Sanchez-Cortes Santiago 
Published: December 2022

Abstract
Background
Mushrooms have always been considered an important source of food and biologically active compounds with several medicinal properties. In recent years, different methods were used to study the quality and chemical composition of mushrooms. Among these, Fourier transform infrared (FT-IR) and FT-Raman spectroscopy techniques have been successfully applied to identify different mushroom species. However, the structural biomolecule components existing in the mycelium or in the fruiting bodies may produce strong fluorescence emission that overlaps the Raman radiation, thus avoiding their analyses by Raman. SERS spectroscopy is a powerful technique which uses metal nanoparticles (NPs) to enhance the Raman signal of molecules adsorbed on the NPs surface. In addition, SERS is able to quench the macromolecule florescence. In this work, we have employed silver nanoparticles in order to get mushroom fingerprints based on SERS as quick procedure to analyze and identify different chemical compounds from the fruiting bodies of six edible and/or medicinal mushrooms: Lentinula edodes, Ganoderma lucidum, Pleurotus cornucopiae, Pleurotus ostreatus, Tuber aestivum and Tuber magnatum.

Results
SERS analyses performed directly on fruiting body fragments produced characteristic spectra for each species. One group of mushrooms (L. edodes, G. lucidum, T. aestivum and T. magnatum) was dominated by the bands of nucleic acids; and the other one (P. cornucopiae and P. ostreatus), by the bands of pigments such as melanins; carotenoids; azafilones; polyketides; and flavonoids located in the cell wall. Additionally, bands corresponding to cell wall polysaccharides, particularly chitosan and 1,3-β D-glucan, were identified in the extracts of P. cornucopiae, P. ostreatus and L. edodes. No signal of cell wall polysaccharides was found in G. lucidum extract. Raman mapping of the analyzed samples was useful in tracking the spatial distribution of the marker bands. Moreover, the principal component analysis (PCA) carried out on the acquired SERS spectra, allows to discriminate the analyzed mushroom species.

Conclusions
The SERS technique has the ability to generate a strong Raman signal from mushroom fruiting bodies using Ag-NPs deposited directly on intact, untreated mushroom tissues. Using this methodology, commonly applied laboratory time-consuming methods can be avoided or bypassed as well as analysis time can be reduced.

Graphical Abstract
Microbiome and metagenomic analysis of Lake Hillier Australia reveals pigment-rich polyextremophiles and wide-ranging metabolic adaptations
Authors: Sierra Maria A. , Ryon Krista A. , Tierney Braden T. , Foox Jonathan , Bhattacharya Chandrima , Afshin Evan , Butler Daniel , Green Stefan J. , Thomas W. Kelley , Ramsdell Jordan , Bivens Nathan J. , McGrath Ken , Mason Christopher E. , Tighe Scott W. 
Published: December 2022

AbstractLake Hillier is a hypersaline lake known for its distinctive bright pink color. The cause of this phenomenon in other hypersaline sites has been attributed to halophiles, Dunaliella, and Salinibacter, however, a systematic analysis of the microbial communities, their functional features, and the prevalence of pigment-producing-metabolisms has not been previously studied. Through metagenomic sequencing and culture-based approaches, our results evidence that Lake Hillier is composed of a diverse set of microorganisms including archaea, bacteria, algae, and viruses. Our data indicate that the microbiome in Lake Hillier is composed of multiple pigment-producer microbes, including Dunaliella, Salinibacter, Halobacillus, Psychroflexus, Halorubrum, many of which are cataloged as polyextremophiles. Additionally, we estimated the diversity of metabolic pathways in the lake and determined that many of these are related to pigment production. We reconstructed complete or partial genomes for 21 discrete bacteria (N = 14) and archaea (N = 7), only 2 of which could be taxonomically annotated to previously observed species. Our findings provide the first metagenomic study to decipher the source of the pink color of Australia’s Lake Hillier. The study of this pink hypersaline environment is evidence of a microbial consortium of pigment producers, a repertoire of polyextremophiles, a core microbiome and potentially novel species.