bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis on factors behind sentinel lymph node metastasis in breast cancer by color ultrasonography, molybdenum target, and pathological detection
Authors: Yiming Aibibai , Wubulikasimu Muhetaer , Yusuying Nuermaimaiti 
Published: March 2022

Abstract
Background
This study aimed to identify the factors underlying the metastasis of breast cancer and sentinel lymph nodes and to screen and analyze the risk factors of sentinel lymph node metastasis to provide a reference and basis for clinical work.

Methods
A total of 99 patients with breast cancer were enrolled in this study. These patients received treatment in our hospital between May 2017 and May 2020. The general information, characteristics of the color Doppler echocardiography, molybdenum, conventional pathology, and molecular pathology of the patients were collected. Factors influencing sentinel lymph node metastasis in breast cancer patients were retrospectively analyzed.

Results
In this study, age, tumor diameter, BI-RADS category, pathology type, expression profiles of CK5/6, EGFR, and CK19, and TP53 and BRAC1/2 mutations were independent risk factors for sentinel lymph node metastasis in breast cancer (P < 0.05). The number and locations of tumors, quadrant of tumors, regularity of tumor margins, presence of blood flow signals, presence of posterior echo attenuation, presence of calcification, histological grade, molecular typing, and mutations of BRAF, ATM, and PALB2 were irrelevant factors (P > 0.05).

Conclusions
In conclusion, age, tumor diameter, BI-RADS category, invasive type, expression of CK5/6, EGFR, and CK19, and mutations in TP53 and BRAC1/2 were positively correlated with sentinel lymph node metastasis. These independent risk factors should be given more attention in clinical studies to strengthen the management and control of sentinel lymph node metastasis in high-risk breast cancer and support early chemotherapy or targeted therapy.
Investigating the impact of SARS-CoV-2 infection on basic semen parameters and in vitro fertilization/intracytoplasmic sperm injection outcomes: a retrospective cohort study
Authors: Wang Meng , Hu Juan , Huang Bo , Yang Qiyu , Liu Sibo , Li Zhou , Yang Liu , Xi Qingsong , Zhu Lixia , Jin Lei 
Published: March 2022

Abstract
Background
This study aimed to evaluate the influences of SARS-CoV-2 infection on semen parameters and investigate the impact of the infection on in vitro fertilization (IVF) outcomes.

Methods
This retrospective study enrolled couples undergoing IVF cycles between May 2020 and February 2021 at Tongji Hospital, Wuhan. Baseline characteristics were matched using propensity score matching. Participants were categorized into an unexposed group (SARS-COV-2 negative) and exposed group (SARS-COV-2 positive) based on a history of SARS-CoV-2 infection, and the populations were 148 and 50 after matching, respectively. IVF data were compared between the matched cohorts. Moreover, semen parameters were compared before and after infection among the infected males. The main measures were semen parameters and IVF outcomes, including laboratory and clinical outcomes.

Results
Generally, the concentration and motility of sperm did not significantly differ before and after infection. Infected males seemed to have fewer sperm with normal morphology, while all values were above the limits. Notably, the blastocyst formation rate and available blastocyst rate in the exposed group were lower than those in the control group, despite similar mature oocytes rates, normal fertilization rates, cleavage rates, and high-quality embryo rates. Moreover, no significant differences were exhibited between the matched cohorts regarding the implantation rate, biochemical pregnancy rate, clinical pregnancy rate, or early miscarriage rate.

Conclusions
The results of this retrospective cohort study suggested that the semen quality and the chance of pregnancy in terms of IVF outcomes were comparable between the males with a history of SARS-CoV-2 infection and controls, although a decreased blastocyst formation rate and available blastocyst rate was observed in the exposed group, which needs to be reinforced by a multicenter long-term investigation with a larger sample size.
An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile
Authors: De Angelis Maria Laura , Francescangeli Federica , Nicolazzo Chiara , Signore Michele , Giuliani Alessandro , Colace Lidia , Boe Alessandra , Magri Valentina , Baiocchi Marta , Ciardi Antonio , Scarola Francesco , Spada Massimo , La Torre Filippo , Gazzaniga Paola , Biffoni Mauro , De Maria Ruggero , Zeuner Ann 
Published: March 2022

Abstract
Background
Circulating tumor cells (CTCs) are responsible for the metastatic dissemination of colorectal cancer (CRC) to the liver, lungs and lymph nodes. CTCs rarity and heterogeneity strongly limit the elucidation of their biological features, as well as preclinical drug sensitivity studies aimed at metastasis prevention.

Methods
We generated organoids from CTCs isolated from an orthotopic CRC xenograft model. CTCs-derived organoids (CTCDOs) were characterized through proteome profiling, immunohistochemistry, immunofluorescence, flow cytometry, tumor-forming capacity and drug screening assays. The expression of intra- and extracellular markers found in CTCDOs was validated on CTCs isolated from the peripheral blood of CRC patients.

Results
CTCDOs exhibited a hybrid epithelial-mesenchymal transition (EMT) state and an increased expression of stemness-associated markers including the two homeobox transcription factors Goosecoid and Pancreatic Duodenal Homeobox Gene-1 (PDX1), which were also detected in CTCs from CRC patients. Functionally, CTCDOs showed a higher migratory/invasive ability and a different response to pathway-targeted drugs as compared to xenograft-derived organoids (XDOs). Specifically, CTCDOs were more sensitive than XDOs to drugs affecting the Survivin pathway, which decreased the levels of Survivin and X-Linked Inhibitor of Apoptosis Protein (XIAP) inducing CTCDOs death.

Conclusions
These results indicate that CTCDOs recapitulate several features of colorectal CTCs and may be used to investigate the features of metastatic CRC cells, to identify new prognostic biomarkers and to devise new potential strategies for metastasis prevention.
Prediction of knee osteoarthritis progression using radiological descriptors obtained from bone texture analysis and Siamese neural networks: data from OAI and MOST cohorts
Authors: Almhdie-Imjabbar Ahmad , Nguyen Khac-Lan , Toumi Hechmi , Jennane Rachid , Lespessailles Eric 
Published: March 2022

Abstract
Background
Trabecular bone texture (TBT) analysis has been identified as an imaging biomarker that provides information on trabecular bone changes due to knee osteoarthritis (KOA). In parallel with the improvement in medical imaging technologies, machine learning methods have received growing interest in the scientific osteoarthritis community to potentially provide clinicians with prognostic data from conventional knee X-ray datasets, in particular from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST) cohorts.

Patients and methods
This study included 1888 patients from OAI and 683 patients from MOST cohorts. Radiographs were automatically segmented to determine 16 regions of interest. Patients with an early stage of OA risk, with Kellgren and Lawrence (KL) grade of 1 < KL < 4, were selected. The definition of OA progression was an increase in the OARSI medial joint space narrowing (mJSN) grades over 48 months in OAI and 60 months in MOST. The performance of the TBT-CNN model was evaluated and compared to well-known prediction models using logistic regression.

Results
The TBT-CNN model was predictive of the JSN progression with an area under the curve (AUC) up to 0.75 in OAI and 0.81 in MOST. The predictive ability of the TBT-CNN model was invariant with respect to the acquisition modality or image quality. The prediction models performed significantly better with estimated KL (KLprob) grades than those provided by radiologists. TBT-based models significantly outperformed KLprob-based models in MOST and provided similar performances in OAI. In addition, the combined model, when trained in one cohort, was able to predict OA progression in the other cohort.

Conclusion
The proposed combined model provides a good performance in the prediction of mJSN over 4 to 6 years in patients with relevant KOA. Furthermore, the current study presents an important contribution in showing that TBT-based OA prediction models can work with different databases.
Novel diagnostic tools for identifying cognitive impairment using olfactory-stimulated functional near-infrared spectroscopy: patient-level, single-group, diagnostic trial
Authors: Kim Jaewon , Yon Dong Keon , Choi Kyu Yeong , Lee Jang Jae , Kim Namwoo , Lee Kun Ho , Kim Jae Gwan 
Published: March 2022

Abstract
Introduction
Basic studies suggest that olfactory dysfunction and functional near-infrared spectroscopy (fNIRS) can be used as tools for the diagnosis of mild cognitive impairment (MCI); however, real-world evidence is lacking. We investigated the potential diagnostic efficacy of olfactory-stimulated fNIRS for early detection of MCI and/or Alzheimer disease (AD).

Methods
We conducted a patient-level, single-group, diagnostic interventional trial involving elderly volunteers (age >60 years) suspected of declining cognitive function. Patients received open-label olfactory-stimulated fNIRS for measurement of oxygenation difference in the orbitofrontal cortex. All participants underwent amyloid PET, MRI, Mini-Mental State Examination (MMSE), and Seoul Neuropsychological Screening Battery (SNSB).

Results
Of 97 subjects, 28 (28.9%) were cognitively normal, 32 (33.0%) had preclinical AD, 21 (21.6%) had MCI, and 16 (16.5%) had AD. Olfactory-stimulated oxygenation differences in the orbitofrontal cortex were associated with cognitive impairment; the association was more pronounced with cognitive severity. Olfactory-stimulated oxygenation difference was associated with MMSE (adjusted β [aβ] 1.001; 95% CI 0.540−1.463), SNSB language and related function (aβ, 1.218; 95% CI, 0.020−2.417), SNSB memory (aβ, 1.963; 95% CI, 0.841−3.084), SNSB frontal/executive function (aβ, 1.715; 95% CI, 0.401−3.029) scores, standard uptake value ratio from amyloid PET (aβ, −10.083; 95% CI, −19.063 to −1.103), and hippocampal volume from MRI (aβ, 0.002; 95% CI, 0.001−0.004). Olfactory-stimulated oxygenation difference in the orbitofrontal cortex was superior in diagnosing MCI and AD (AUC, 0.909; 95% CI, 0.848−0.971), compared to amyloid PET (AUC, 0.793; 95% CI, 0.694−0.893) or MRI (AUC, 0.758; 95% CI, 0.644−0.871).

Discussion
Our trial showed that olfactory-stimulated oxygenation differences in the orbitofrontal cortex detected by fNIRS were associated with cognitive impairment and cognitive-related objectives. This novel approach may be a potential diagnostic tool for patients with MCI and/or AD.

Trial registration
CRIS number, KCT0006197.
Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer’s disease with an implantable ultrasound device
Authors: Epelbaum Stéphane , Burgos Ninon , Canney Michael , Matthews Dawn , Houot Marion , Santin Mathieu D. , Desseaux Carole , Bouchoux Guillaume , Stroer Sebastian , Martin Cyril , Habert Marie-Odile , Levy Marcel , Bah Aicha , Martin Karine , Delatour Benoît , Riche Maximilien , Dubois Bruno , Belin Lisa , Carpentier Alexandre 
Published: March 2022

AbstractBackgroundTemporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer’s disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and efficacy of this approach in patients with mild AD using an implantable ultrasound device.MethodsAn implantable, 1-MHz ultrasound device (SonoCloud-1) was implanted under local anesthesia in the skull (extradural) of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB.18F-florbetapir and18F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at 4 and 8 months after the initiation of sonications to monitor the brain metabolism and amyloid levels along with cognitive evaluations. The evolution of cognitive and neuroimaging features was compared to that of a matched sample of control participants taken from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).ResultsA total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at 4 months of − 6.6% (SD = 7.2%) on18F-florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in the longitudinal change in the glucose metabolism were observed compared to the neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison with the ADNI participants as expected due to the small sample size and duration of the trial.ConclusionsThese results demonstrate the safety of ultrasound-based BBB disruption and the potential of this technology to be used as a therapy for AD patients. Research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease-modifying drugs may further enhance the effects observed.Trial registrationClinicalTrials.gov,NCT03119961
Effects of different amino acid levels and a carvacrol–thymol blend on growth performance and intestinal health of weaned pigs
Authors: Wang Yanan , Yang Zhipeng , Zhou Yuanfei , Tan Jiajian , Sun Haiqing , Sun Defa , Mu Yuyun , Peng Jian , Wei Hongkui 
Published: March 2022

Abstract
Background
Over the past years, antibiotic growth promoter had been restricted in animal husbandry production in many countries because of antimicrobial resistance and foodborne antibiotic residues. However, the problems of poor intestinal health and low growth efficiency of piglets have not been solved completely in an antibiotic-free diet, and it is urgent to explore alternatives to antimicrobial growth promoters.

Methods
Here, a total of 532 weaned pigs were assigned to one of 4 treatments, the low amino acid (AA) level diet (d 1 to d 14 is 1.35%, d 15 to d 42 is 1.25%) (Low AA), the low AA level diet supplementation with a carvacrol–thymol blend (50 mg carvacrol and 50 mg thymol/kg of diet) (CB) (Low AA+CB), the high AA level diet (d 1 to d 14 is 1.50%, d 15 to d 42 is 1.40%) (High AA), and the high AA level diet supplementation with a CB (High AA+CB), respectively. Then we measured growth performance and intestinal health indicators of weaned pigs.

Results
Results showed that high AA level significantly reduced plasma urea nitrogen, plasma Interleukin-6 (IL-6) and fecal lipocalin-2 contents (P <  0.05), significantly increased the relative abundance of fecal Lactobacillus and Enterococcus, and had a trend to increase the fecal secretory immunoglobulin A (sIgA) and mucin 2 (MUC 2) contents (P <  0.05) in piglets, thereby alleviating the diarrhea of piglets and reducing the feed conversion ratio (FCR) of piglets during d 1~14 after weaning. Dietary supplementation with CB significantly increased the activity of plasma antioxidant enzymes T-SOD and GSH-px (P <  0.05), while significantly reduced plasma malondialdehyde (MDA), plasma interleukin-1β (IL-1β), plasma endotoxin and D-lactic acid contents (P <  0.05). Meanwhile, CB significantly decreased fecal lipocalin-2 contents and the abundance of fecal Escherichia coli (P < 0.05). Thus, we hypothesis that dietary supplementation with CB significantly increased the average daily gain (ADG) of piglets (P < 0.05) during d 1~14 after weaning through promoting intestinal health.

Conclusion
These results suggest that high AA level and dietary supplementation with CB improved the growth performance of weaned pigs in an antibiotic-free diet by improving AA metabolism and intestinal antioxidant capacity.
Immunogenetic variation shapes the gut microbiome in a natural vertebrate population
Authors: Davies Charli S. , Worsley Sarah F. , Maher Kathryn H. , Komdeur Jan , Burke Terry , Dugdale Hannah L. , Richardson David S. 
Published: March 2022

AbstractBackgroundThe gut microbiome (GM) can influence many biological processes in the host, impacting its health and survival, but the GM can also be influenced by the host’s traits. In vertebrates, Major Histocompatibility Complex (MHC) genes play a pivotal role in combatting pathogens and are thought to shape the host’s GM. Despite this—and the documented importance of both GM and MHC variation to individual fitness—few studies have investigated the association between the GM and MHC in the wild.ResultsWe characterised MHC class I (MHC-I), MHC class II (MHC-II) and GM variation in individuals within a natural population of the Seychelles warbler (Acrocephalus sechellensis). We determined how the diversity and composition of the GM varied with MHC characteristics, in addition to environmental factors and other host traits. Our results show that the presence of specific MHC alleles, but not MHC diversity, influences both the diversity and composition of the GM in this population. MHC-I alleles, rather than MHC-II alleles, had the greatest impact on the GM. GM diversity was negatively associated with the presence of three MHC-I alleles (Ase-ua3, Ase-ua4, Ase-ua5), and one MHC-II allele (Ase-dab4), while changes in GM composition were associated with the presence of four different MHC-I alleles (Ase-ua1, Ase-ua7, Ase-ua10, Ase-ua11). There were no associations between GM diversity andTLR3genotype, but GM diversity was positively correlated with genome-wide heterozygosity and varied with host age and field period.ConclusionsThese results suggest that components of the host’s immune system play a role in shaping the GM of wild animals. Host genotype—specifically MHC-I and to a lesser degree MHC-II variation—can modulate the GM, although whether this occurs directly, or indirectly through effects on host health, is unclear. Importantly, if immune genes can regulate host health through modulation of the microbiome, then it is plausible that the microbiome could also influence selection on immune genes. As such, host–microbiome coevolution may play a role in maintaining functional immunogenetic variation within natural vertebrate populations.
Decisive or impulsive? Re-examining Africa’s lockdown response to COVID-19
Authors: Alaran Aishat Jumoke , Badmos Abubakar Olaitan , Bouaddi Oumnia , Adebisi Yusuff Adebayo , Ben-Umeh Kenechukwu , Idris Umarfarouq , Lucero-Prisno Don Eliseo 
Published: March 2022

AbstractDue to the high transmission rate and mortality index of the current coronavirus pandemic, many settings in Africa instituted lockdowns to reduce its rate of spread and avert exponential growth rate. At the early stage, this measure seemed to heighten awareness of the virus and subsequently minimized exponential growth of cases. However, these lockdowns have had great consequences on the weak health systems and frail economy in place in many African countries. In this paper, we examine the impact of lockdown measures in these countries and provides key recommendations in dealing with present and future pandemics.
Determinants of Neutralizing Antibody Response After SARS CoV-2 Vaccination in Patients With Myeloma
Authors: Nooka Ajay K. , Shanmugasundaram Uma , Cheedarla Narayana , Verkerke Hans , Edara Venkata V. , Valanparambil Rajesh , Kaufman Jonathan L. , Hofmeister Craig C. , Joseph Nisha S. , Lonial Sagar , Azeem Maryam , Manalo Julia , Switchenko Jeffrey M. , Chang Andres , Linderman Susanne L. , Roback John D. , Dhodapkar Kavita M. , Ahmed Rafi , Suthar Mehul S. , Neish Andrew S. , Dhodapkar Madhav V. 
Published: March 2022

PURPOSE Vaccine-induced neutralizing antibodies (nAbs) play a critical role in protection from SARS CoV-2. Patients with B-cell malignancies including myeloma are at increased risk of COVID-19–related mortality and exhibit variable serologic response to the vaccine. The capacity of vaccine-induced antibodies in these patients to neutralize SARS CoV-2 or its variants is not known. METHODS Sera from 238 patients with multiple myeloma (MM) undergoing SARS CoV-2 vaccination were analyzed. Antibodies against the SARS CoV-2 spike receptor-binding domain (RBD) and viral nucleocapsid were measured to detect serologic response to vaccine and environmental exposure to the virus. The capacity of antibodies to neutralize virus was quantified using pseudovirus neutralization assay and live virus neutralization against the initial SARS CoV-2 strain and the B1.617.2 (Delta) variant. RESULTS Vaccine-induced nAbs are detectable at much lower rates (54%) than estimated in previous seroconversion studies in MM, which did not monitor viral neutralization. In 33% of patients, vaccine-induced antispike RBD antibodies lack detectable neutralizing capacity, including against the B1.617.2 variant. Induction of nAbs is affected by race, disease, and treatment-related factors. Patients receiving mRNA1273 vaccine (Moderna) achieved significantly greater induction of nAbs compared with those receiving BNT162b2 (Pfizer; 67% v 48%, P = .006). CONCLUSION These data show that vaccine-induced antibodies in several patients with MM lack detectable virus-neutralizing activity. Vaccine-mediated induction of nAbs is affected by race, disease, vaccine, and treatment characteristics. These data have several implications for the emerging application of booster vaccines in immunocompromised hosts.