bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification and expression analysis of the SET domain-containing gene family in potato (Solanum tuberosum L.)
Authors: Suppiyar Vithusan , Bonthala Venkata Suresh , Shrestha Asis , Krey Stephanie , Stich Benjamin
Published: December 2023

Genes containing the SET domain can catalyse histone lysine methylation, which in turn has the potential to cause changes to chromatin structure and regulation of the transcription of genes involved in diverse physiological and developmental processes. However, the functions of SET domain-containing (StSET) genes in potato still need to be studied. The objectives of our study were to (i) identify StSET genes in the potato genome, (ii) systematically analyse gene structure, chromosomal distribution, gene duplication events, promoter sequences, and protein domains, (iii) perform phylogenetic analyses, (iv) compare the SET domain-containing genes of potato with other plant species with respect to protein domains and orthologous relationships, (v) analyse tissue-specific expression, and (vi) study the expression of StSET genes in response to drought and heat stresses. In this study, we identified 57 StSET genes in the potato genome, and the genes were physically mapped onto eleven chromosomes. The phylogenetic analysis grouped these StSET genes into six clades. We found that tandem duplication through sub-functionalisation has contributed only marginally to the expansion of the StSET gene family. The protein domain TDBD (PFAM ID: PF16135) was detected in StSET genes of potato while it was absent in all other previously studied species. This study described three pollen-specific StSET genes in the potato genome. Expression analysis of four StSET genes under heat and drought in three potato clones revealed that these genes might have non-overlapping roles under different abiotic stress conditions and durations. The present study provides a comprehensive analysis of StSET genes in potatoes, and it serves as a basis for further functional characterisation of StSET genes towards understanding their underpinning biological mechanisms in conferring stress tolerance.
Predicting Monoclonal Antibody Binding Sequences from a Sparse Sampling of All Possible Sequences
Authors: Woodbury Neal , Bisarad Pritha , Kelbauskas Laimonas , Singh Akanksha , Taguchi Alexander
Published: December 2023

A general approach is described for creating a comprehensive and quantitative model for predicting the binding of a monoclonal antibody (mAb) to any short linear sequence of amino acids. Binding of 8 different mAbs with continuous epitopes to a common library of ~122,000 near-random peptide sequences arrayed on a silica substrate was used to train neural network models resulting in a general sequence-binding relationship for each mAb. The model was then used to predict mAb binding to 1,000,000 randomly generated sequences as well as the cognate sequence of each mAb. In every case the cognate sequence ranked in the top 250 sequences, and for 5 of the 8 mAbs it ranked in the top 10 out of one million. Practically, this approach has potential utility in selecting highly specific mAbs for therapeutics or diagnostics. Conceptually, this demonstrates that very sparse, but near random, sampling of a large sequence space is sufficient to generate comprehensive models predictive of highly specific molecular recognition.
Beyond Disaster: Investigating the Varied Responses of Regional Entrepreneurship to Natural Disasters
Authors: Demirdag Ismail , Nirwansyah Anang Widhi
Published: December 2023

Natural disasters can cause large-scale damage to various infrastructures, preventing sustainable industrialization, innovation activities, and economic growth and prosperity. This article, which tries to examine to what extent entrepreneurial activities, which are considered the critical source of new businesses, employment, innovations and economic development, are affected by natural disasters and how the level of impact differs by region, offers remarkable results. First, it employs Hierarchical Multiple Regression (HMR) analysis to investigate the impact of natural disasters on regional entrepreneurship, considering various factors including supply side, demand side, political and environmental factors. An important finding of the research is that loss of human life, rather than physical damage, emerges as a critical factor shaping regional entrepreneurship development. Second, the study utilizes Discriminant Function Analysis (DFA) to identify regional determinants that contribute to the resilience of entrepreneurship in the face of natural disasters. The research highlights the significance of regional features, government policies and environmental conditions in shaping regional entrepreneurial resilience. Future research avenues could investigate the regional impact of specific types of disasters, conduct subsector-specific analyses, and investigate the role of institutional quality in mitigating the effects of disasters at the regional level.
RETRACTED: Illicit and licit drug contamination results on Turkish banknotes in three provinces of Turkey
Authors: Ozturk Yeter Erol , Demirel Goksun , Yeter Oya , Aslıyüksek Hızır
Published: December 2023

The authors have requested that this preprint be removed from Research Square.
DNMT3L Inhibits Hepatocellular Carcinoma Progression through DNA Methylation of CDO1: Insights from Big Data to Basic Research
Authors: Yan Xiaokai , Qi Yao , Yao Xinyue , Zhou Nanjing , Ye Xinxin , Chen Xing
Published: December 2023

Background
DNMT3L is a crucial DNA methylation regulatory factor, yet its function and mechanism in hepatocellular carcinoma (HCC) remain poorly understood. Bioinformatics-based big data analysis has increasingly gained significance in cancer research. Therefore, this study aims to elucidate the role of DNMT3L in HCC by integrating big data analysis with experimental validation.
Methods
Dozens of HCC datasets were collected to analyze the expression of DNMT3L and its relationship with prognostic indicators, and were used for molecular regulatory relationship evaluation. The effects of DNMT3L on the malignant phenotypes of hepatoma cells were confirmed in vitro and in vivo. The regulatory mechanisms of DNMT3L were explored through MSP, western blot, and dual-luciferase assays.
Results
DNMT3L was found to be downregulated in HCC tissues and associated with better prognosis. Overexpression of DNMT3L inhibits cell proliferation and metastasis. Additionally, CDO1 was identified as a target gene of DNMT3L and also exhibits anti-cancer effects. DNMT3L upregulates CDO1 expression by competitively inhibiting DNMT3A-mediated methylation of CDO1 promoter.
Conclusions
Our study revealed the role and epi-transcriptomic regulatory mechanism of DNMT3L in HCC, and underscored the essential role and applicability of big data analysis in elucidating complex biological processes.
Comparison of models for predicting intracranial pressure by optic nerve sheath diameter in combination with other indicators: A study based on ultrasound measurements
Authors: cheng Mingqing , Liu Tingting , Guo Geng , Hui Zili , Zhang Lei , Hu Jianqiang , Zhang Jing , Fang Yalan
Published: December 2023

Introduction:
The optic nerve sheath diameter (ONSD) assessment of elevated intracranial pressure is increasingly emphasized as a noninvasive modality. Still, quantitative assessment is less common in current studies, and study criteria are variable. We constructed four prediction models related to ONSD and compared their accuracy in predicting intracranial pressure (ICP).
Methods
This study included 223 patients who completed lumbar puncture (LP) at the First Hospital of Shanxi Medical University with values of ICP and Mindray-M58 ultrasound-measured ONSD, optic nerve sheath (OND), and eyeball transverse diameter (ETD). The patients were randomly assigned 7:3 to model and test groups, and predictive models (ONSD model, ONSD combined OND model, ΔONSD model, and ONSD/ETD model) were established in the model group using linear regression analysis. The test group evaluated the agreement between the models' predicted and actual ICP values using Bland‒Altman analysis and the intragroup correlation coefficient (ICC).
Results
ICP values were strongly correlated with ΔONSD, ONSD, and ONSD/ETD. The ONSD combined OND model showed the highest predictive power for increased ICP (area under the receiver operating characteristic curve [AUC] = 0.933). The four mathematical equations established in the model group (n = 154) were as follows: 1. ONSD combined OND model: predicted ICP = 139.394×ONSD-112.428×OND-267.461; 2. ONSD model: predicted ICP = 108.227× ONSD-404.446; 3. ΔONSD model: predicted ICP = 140.216 × ΔONSD-196.335; 4. ONSD/ETD model: predicted ICP = 1624.283×ONSD/ETD-196.904. In the test group (n = 66), it was shown that ONSD combined OND (ICC = 0.88) prediction accuracy was the highest.
Conclusion
Bedside ultrasound measurement of ONSD combined OND is a practical method to assess ICP values. This study indicated that the efficacy of the ONSD combined with the OND model and the ΔONSD model in predicting ICP was better than that of ONSD alone, reflecting the fact that intracranial pressure changes mainly affect the optic nerve sheath rather than the optic nerve.
Study of cabbage antioxidant system response on early infection stage of Xanthomonas campestris pv. campestris
Authors: Liu Zeci , wang Jie , Yue Zhibin , Wang Jue , Dou Tingting , Chen Tongyan , Li Jinbao , Dai Haojie , Yu Jihua
Published: December 2023

Black rot, caused by Xanthomonas campestris pv. campestris (Xcc) significantly affects the production of cabbage and other cruciferous vegetables. Plant antioxidant system plays an important role in pathogen invasion and is one of the main mechanisms underlying resistance to biological stress. Therefore, it is important to study the resistance mechanisms of the cabbage antioxidant system during the early stages of Xcc. In this study, Xcc race1 was inoculated on "zhonggan 11" cabbage using the spraying method. The effects of Xcc infection on the antioxidant system before and after Xcc inoculation were studied by physiological indexes determination and transcriptome and metabolome analyses. We concluded that early Xcc infection can destroy the balance of the active oxygen metabolism system, increase the generation of free radicals, and decrease the scavenging ability, leading to membrane lipid peroxidation, resulting in the destruction of the biofilm system and metabolic disorders. In response to Xcc infection, cabbage clears a series of reactive oxygen species (ROS) produced during Xcc infection via various antioxidant pathways. The activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased after Xcc infection, and the ROS scavenging rate increased. The biosynthesis of non-obligate antioxidants, such as ascorbic acid (AsA) and glutathione (GSH), is also enhanced after Xcc infection. Moreover, the alkaloid and vitamin contents increased significantly after Xcc infection. We concluded that cabbage could resist Xcc invasion by maintaining the stability of the cell membrane system and improving the biosynthesis of antioxidant substances and enzymes after infection by Xcc. Our results provide a theoretical basis for subsequent research on the cabbage’s resistance mechanism to Xcc.
Isolation and characterization of lytic bacteriophages from various sources in Addis Ababa against antimicrobial-resistant diarrheagenic Escherichia coli strains and evaluation of their therapeutic Potential
Authors: Sada Tamirat Salile , Tessema Tesfaye Sisay
Published: December 2023

Escherichia coli is a common fecal coliform, facultative aerobic, gram-negative bacterium. Pathogenic strains of such microbes have evolved to cause diarrhea, urinary tract infections, and septicemias. The emergence of antibiotic resistance urged the identification of an alternative strategy. The use of lytic bacteriophages against the control of pathogenic E. coli in clinics and different environmental setups (waste and drink water management) has become an alternative therapy to antibiotic therapy. Thus, this study aimed to isolate and characterize lytic bacteriophage from various sources in Addis Ababa, tested them against antimicrobial-resistant diarrheagenic E. coli strains and evaluated their therapeutic potential under in vitro conditions. A total of 14 samples were processed against six different diarrheagenic E. coli strains. The conventional culture and plaque analysis agar overlay method was used to recover lytic bacteriophage isolates. The phage isolates were characterized to determine their lytic effect, growth characteristics, host range activity and stability under different temperature and pH conditions. Phage isolates were identified by scanning electron microscope (SEM), and molecular techniques (PCR). In total, 17 phages were recovered from 84 tested plates. Of the 17 phage isolates, 11 (65%) were Myoviridae-like phages, and 6 (35%) phage isolates were Podoviridae and Siphoviridae by morphology and PCR identification. Based on the host range test, growth characteristics and stability test 7 potent phages were selected. These phages demonstrated better growth characteristics, including short latent periods, highest burst sizes, and wider host ranges, as well as thermal stability and the ability to survive in a wide range of pH levels. The promising effect of these phages against AMR pathogens has raised the possibility of their use in the biological control of bacterial infections.
YouTube as a Source of Recognizing Acute Stroke; Progress in 2 years
Authors: özdemir zeynep , acar erkan
Published: December 2023

Background
YouTube™ has a great role in providing information, which includes educational videos, to more than 2 billion users, making it the second most popular application in the world. BE-FAST is a modified version of the FAST mnemonic and is used to detect acute ischemic stroke by the patients or their relatives. The purpose of this study is to assess the overall usefulness of the information of YouTube in acute stroke patients.
Methods
YouTube was searched for the following five terms: “stroke”, ‘‘stroke diagnosis”, “stroke signs”, “brain attack” and “what is stroke” in November 2021 and May 2023, separately. Two independent neurology specialists scored each video by using Global Quality Scale (GQS).
Results
Among the total of 150 videos, the number that met inclusion criteria was 91 for the November 2021 search and 104 for the May 2023 search. For the 2021 search, in 30 videos (33%), the FAST mnemonic or its contents were noticed, whereas BE-FAST was mentioned in only four videos (4.4%). For the 2023 search, the FAST mnemonic or its contents were noticed in 36 videos (34.6%) and BE-FAST was mentioned in 11 videos (10.6%). Among the 2021 and 2023 searches, the mean GQS values were 3.09 and 2.96 points, 50 (54.8%) vs 56 (53.8%) videos rated 3.5 points or higher (high quality), respectively. GQS scores of the videos mentioning balance, eyes, face, arms, speech, and time, the basic and further information about radiology and treatment, and mentioning FAST, BE-FAST, and TPA were significantly higher.
Conclusion
We conclude that YouTube is not yet useful enough to detect acute ischemic stroke, though has made positive progress with the developing use of social media for healthcare information and education.
MicroRNA-297 exerts angiogenesis and cardioprotection after myocardial infarction via through targeting FTO-dependent m6A
Authors: Sun Tong , Zhang Qian , Wang Lingzhun , Zhu Junfeng , Han Jie , Zhao Xinsui , Chen Xiaohu , Tang Shuhua , Chen Jiandong
Published: December 2023

Background
Emerging evidence suggests that microRNA (miRNA) and m6A RNA methylation are involved Pathogenesis of a variety of cardiovascular diseases, including myocardial infarction. However, the potential role of m6A in regulating ischemic cardiac regeneration and angiogenesis remains unclear. In this study, the effects of our microRNA-297 (miR-297) on myocardial infarction and endothelial cell damage.
Methods
The intermodulation of miR-297/FTO/VEGF axes was verified by RT-qPCR, western blotting, m6A quantitative assay and Di luciferase reporter detection. At the same time, the expression, function and prognosis of miR-297 in myocardial infarction were studied through RT-qPCR, western blotting and rescue experiments.
Results
In this study, we identified the downregulation of m6A demethylase FTO and miR-297 in cardiac and hypoxia-induced HUVEC cells after myocardial infarction. The expression of miR-297 significantly inhibited proliferation, migration, and angiogenesis, while knocked down miR-297 had the opposite effect. After myocardial infarction in mice, forced expression of miR-297 by adeno-associated virus significantly decreases expression of VEGF and weakens cardiac function, while simultaneous increased expression of FTO can reverse this effect. Thus, a feedback loop containing the miR-297/FTO/VEGF axis is formed.
Conclusion
miRNA is involved in m6A-mediated cardiac protection. Determining the role of m6A-regulated miRNAs in cardiac protection may provide new therapeutic and preventive targets for ischemic heart disease.
A landscape of energy metabolism as essential role in apical hook development of Arabidopsis etiolated seedlings
Authors: chen Jiahong , Yang Lei , Wang Yuan , Zhang Hehua , Ruan junbin
Published: December 2023

Dicotyledonous plants form an apical hook structure in attempt to protect their young cotyledons from mechanical damage as they break out from the coarse soil. In agricultural production, farmers sometimes apply glucose to the soil to improve plant growth performance. Here, we found that the energy molecules, such as sucrose and glucose, play an essential role in the apical hook development. When sucrose and glucose were available, the apical hooks were able to be sustained longer compared to that grown in sugar-free conditions. And this phenomenon is dose-dependent. Several energy metabolisms pathways, such as oxidative phosphorylation and glycolysis, play highly important roles in the apical hook development. Furthermore, RNA-seq data showed that the genes involved in starch and sucrose metabolism were up-regulated in plants grown in sugar-free conditions compared to that grown in sugar-treated plants, while genes related to phenylpropanoid metabolism were down-regulated. Our study demonstrated the important role of energy metabolism during the apical hook development of Arabidopsisetiolated seedlings.
Functional analysis of a wheat class III peroxidase gene, TaPer12-3A, in seed dormancy and germination
Authors: Gao Wei , Jiang Yating , Yang Xiaohu , Li Ting , Zhang Litian , Yan Shengnan , Cao Jiajia , Lu Jie , Ma Chuanxi , Chang Cheng , Zhang Hai-ping
Published: December 2023

Background
Class III peroxidases (PODs) perform crucial functions in various developmental processes and responses to biotic and abiotic stresses. However, their roles in wheat seed dormancy (SD) and germination remain elusive.
Results
Here, we identified a wheat class III POD gene, named TaPer12-3A, based on transcriptome data and expression analysis. TaPer12-3A showed decreasing and increasing expression trends with SD acquisition and release, respectively. It was highly expressed in wheat seeds and localized in the endoplasmic reticulum and cytoplasm. Germination tests were performed using transgenic Arabidopsis and rice lines as well as wheat mutant mutagenized with ethyl methane sulfonate (EMS) in a Jing 411 (J411) background. These tests indicated that TaPer12-3A negatively regulated SD and positively mediated germination. Further studies showed that TaPer12-3A maintained H2O2 homeostasis by scavenging excess H2O2 and participated in the biosynthesis and catabolism of gibberellic acid and abscisic acid to regulate SD and germination.
Conclusion
These findings not only provide new insights for future functional analysis of TaPer12-3A in regulating wheat SD and germination but also provide a target gene for breeding wheat varieties with high SD and pre-harvest sprouting resistance by gene editing technology.
Sirolimus-Induced Pulmonary Toxicity without Recurrence more than 8 Years after Everolimus Replacement in a Renal Transplant Patient with Recurrent Skin SCC: A Case Report
Authors: Ghasemi Golsa , Shahidi Shahrzad
Published: December 2023

Background: IP (Interstitial Pneumonitis) is one of the pulmonary complications associated with mTOR-Is (mammalian Target of Rapamycin-Inhibitors). Sirolimus and Everolimus belong to mTOR-Is. According to studies, IP is caused by both.
Case presentation: We want to present a case of IP after 50 months of Sirolimus consumption. Sirolimus was discontinued, and Cyclosporine was started. Thirty-seven months later, Everolimus was prescribed as an alternative to Cyclosporine due to the recurrence of skin SCC (Squamous Cell Carcinoma). Fortunately, no respiratory manifestations were seen after more than 8 years of Everolimus consumption.
Conclusions: In conclusion, in cases with Sirolimus-induced IP, discontinuation of Sirolimus and replacement with Everolimus are recommended after resolving clinical symptoms and pulmonary lesions.
Penoscrotal Transposition: Long-term Outcome in 29 Patients
Authors: Perez Dolev , Kocherov Stanislav , Jaber Gaudat , Raisin Galiya , Chertin Boris
Published: December 2023

Objective
Penoscrotal transposition (PST) is a rare anomaly of the external genitalia characterized by malposition of the penis in relation to the scrotum. This transposition may be partial or complete and may be associated with hypospadias and chordee, as well as other anomalies. We have reviewed our experience with the surgical repair of PST utilizing a modified Glenn-Anderson technique.
Material and Methods
Twenty-nine patients with a median age of 5.6 years (8 months -15 years) underwent surgical repair of PST at our institution between 2004-2022. Of those, 20 (69%) had complete PST, while 9 (31%) had partial PST. All children were divided into three groups; In the first group of 8 (28%) children, repair of PST was an integral part of one-stage male genitoplasty; in the second group of 18 (62%) children, repair of PST was an isolated last stage of the staged hypospadias repair, and the remaining 3 (10%) children underwent PST repair without the presence of hypospadias. All patients underwent modification of the Glenn-Anderson technique involving utilization of bilateral rotational advancement scrotal flap, complete de-tethering of the testis from the internal part of the scrotum when indicated, and relocation of the scrotal compartment in a normal dependent position. The follow-up ranged from 6 months to 18 years.
Results
In the first group, five children (62%) underwent Onlay Prepucial Island Pedicle Flap (OIF) hypospadias repair, and three (38%) underwent Long Tubularized Incised Plate Repair (TIP).
In the second group, 8 (44%) underwent OIF hypospadias repair, 2 (12%) had Long TIP repair, and the remaining 8 (44%) underwent staged hypospadias repair. Post-operative Clavien Dindo grade III presented among three patients in group I and only in one patient in group II. In the third group, no postoperative complications were observed.
Conclusions
Our data show that penoscrotal transposition correction utilizing the Glenn-Anderson technique is a reliable and durable surgery in the pediatric population. These children require careful monitoring till adolescence to ensure that no re-operation is needed.
Ecological differentiation of the halophyte Suaeda salsa under different habitat conditions
Authors: Wang Zhaohua , Pan Jiankun , Gao Ting , Wang Qiang , Zhou Daquan , Dong Xiaoyu , Yang Hongxiao , Zhang Xinfang
Published: December 2023

Suaeda salsa serves as an excellent species for environmental remediation in saline-alkali areas. However, its ecological differentiation in different habitats is not clear. Therefore, plant samples of S. salsa from two main habitats in northern China, including populations of saltmarshes and inland were collected, and their differences in external morphology, gene and chemical composition were comprehensively compared. The results showed 1) the basic composition of various organs of S. salsa plants in two habitats was consistent, but there were certain differences in height, color, size, etc. 2) 102 psbA-trnH sequences of S. salsa under different habitats belonged to two distinct haplotypes, with a high level of intraspecific genetic variation. The NJ phylogenetic tree analysis revealed the psbA-trnH sequence successfully distinguished 105 samples of S. salsa from two different habitats. 3) A total of 699 differential metabolites were detected in the two different habitats of S. salsa. The results showed that S. salsa populations were morphologically, genetically and chemically differentiated in different habitats, but there was no substantial difference in the characteristics of reproductive organs. Based on the above analysis, we concluded that S. salsa produced different ecotypes at morphological, genetic and chemical levels to adapt to different habitats.
The usefulness of the MALDI TOF MS technique in the determination of dairy samples microbial composition – comparison of new EXS 2600 system with MALDI Biotyper platform
Authors: Czeszewska-Rosiak Grażyna , Złoch Michał , Radosińska Monika , Florkiewicz Aleksandra Bogumiła , Tretyn Andrzej , Pomastowski Paweł
Published: December 2023

This study compared the EXS 2600 system with the MALDI Biotyper for identifying microorganisms in dairy samples. Of the 196 bacterial isolates from milk, whey, buttermilk, cream, and dairy wastewater, the species and genus consistent identification between two systems showed 74% and 99%, respectively. However, the microorganism’s species identification rate exhibited distinct difference of Zybio 76.0% higher than Bruker 66.8%. Notably, the EXS 2600 system performed better with certain yeast species and H. alvei, while the Biotyper excelled with Pseudomonas bacteria. Unique microbial compositions were found in 85% of dairy samples, with whey and buttermilk having the highest diversity. This research highlights the EXS 2600's potential as a reliable dairy microbial identification tool and underscores the need for a more diverse and comprehensive spectral database, despite the database's focus on clinical applications (as announced ).
Survival and hormone production of isolated mouse follicles in three-dimensional artificial scaffolds after stimulation with bpV(HOpic)
Authors: Keckstein Philip , Dittrich Ralf , Bleisinger Nathalie , Hoffmann Inge , Beckmann Matthias W. , Gebhardt Albrecht , Schmid Benjamin , Keckstein Simon
Published: December 2023

Purpose:
To preserve fertility before gonadotoxic therapy, ovarian tissue can be removed, cryopreserved, and transplanted back again after treatment. An alternative is the artificial ovary, in which the ovarian follicles are extracted from the tissue, which reduces the risk of reimplantation of poten-tially remaining malignant cells. The PTEN inhibitor bpV(HOpic) has been shown to activate human and bovine ovarian follicles, and it is therefore considered a promising substance for de-veloping the artificial ovary.
Methods:
A comparative analysis was performed, studying four different groups that differed either in the scaffold (polycaprolactone scaffold versus polyethylene terephthalate membrane) or in the medium — bpV(HOpic) versus control medium. The observation period was 10 days. On days 2, 6, and 10, the viability and morphology of the mice follicles were checked using fluorescence or confocal microscopy. Furthermore, hormone levels of estrogen (pmol/L) and progesterone (nmol/L) were determined.
Results:
When comparing the survival rates (SR) of follicles among the four groups, it was observed that on day 6, the study groups utilizing the polycaprolactone scaffold with bpV(HOpic) in the me-dium (SR: 0.48 ± 0.18) or functionalized in the scaffold (SR: 0.50 ± 0.20) exhibited significantly higher survival rates compared to the group using only the polyethylene terephthalate membrane (SR: 0.34 ± 0.15). On day 10, a significantly higher survival rate was only noted when comparing the polycaprolactone scaffold with bpV(HOpic) in the medium to the polyethylene terephthalate membrane group (SR: 0.38 ± 0.20 versus 0.21 ± 0.11). Higher levels of progesterone were partly associated with better survival rates, but only reached significance in the group with the poly-caprolactone scaffold functionalized with bpV(HOpic).
Conclusion:
This study demonstrates that three-dimensional polycaprolactone scaffolds improve the survival rates of isolated mice follicles in comparison with a conventional PET membrane. Higher rates of progesterone were also partly associated with improved survival.
Optimize the use of antibiotics in the neonatal intensive care unit: an interrupted time series study
Authors: Zhang Yuanzhen , Chen Li , Chen Xiuping , Li Shiyi , Wang Pengbo , Zhang Yuqin , Nie xiaojing , Chen Guangming
Published: December 2023

Background: This study aims to monitor and evaluate the use of antibiotics in neonates over a 22-month period. The goal is to inform antibiotic stewardship strategies in level 3 neonatal intensive care units (NICU), identify scenarios where antibiotic use could be reduced, and implement interventions while ensuring safety.
Methods: Children admitted to NICU from January 1, 2020, to October 31, 2021, constituted the baseline group, while those admitted from November 1, 2021, to December 31, 2022, formed the intervention group. We employed an interrupted time series to analyze variables including the duration of antibiotic use, length of hospital stay, incidence of hospital-acquired infections, and antibiotic resistance in both groups.
Results: The study involved a total of 1678 infants, with 1138 in the baseline period and 540 in the intervention period. Analysis of antibiotic utilization in patients during the baseline period revealed statistically significant differences in factors such as positive maternal GBS colonization, mechanical ventilation, prematurity, asphyxia resuscitation, premature rupture of membranes at term exceeding 24 hours, elevated inflammatory markers exclusively, and amniotic fluid III° contamination. The rate of antibiotic use decreased from 182.2 days per 1000 patient days in the baseline period to 31.6 days per 1000 patient days in the intervention period. Additionally, the duration of hospitalization, occurrences of nosocomial infections, and the percentage of multidrug-resistant bacteria in blood cultures were significantly lower in the baseline period.
Conclusion: In cases of suspected EOS in children where clear evidence of infection is lacking, judicious administration of antibiotics is recommended. This is particularly important in situations involving pregnant mothers with positive GBS colonization, preterm delivery, contaminated amniotic fluid, elevated inflammatory markers exclusively, premature rupture of membranes in term infants exceeding 24 hours, resuscitation for asphyxia, and mechanical ventilation. Such careful use of antibiotics may lead to a reduction in the duration of antibiotic treatment, a decrease in the occurrence of nosocomial infections, and a lower prevalence of antibiotic-resistant organisms.
Intrathecal pemetrexed in patients with EGFR-TKI resistant refractory leptomeningeal metastasis lung adenocarcinoma : a retrospective study
Authors: Yao Rongrong , Lin Hao , Li Jing , Ge Mengxi , Wang Qing , Liang Xiaohua , Zhou Xinli
Published: December 2023

The incidence of meningeal metastasis in lung adenocarcinoma with EGFR mutation is increasing annually. Refractory meningeal metastasis following EGFR-TKI resistance has no effective treatment and a lethal complication of tumors. The purpose of this study was to evaluate the potential antitumor efficacy and safety of intrathecal pemetrexed in patients with EGFR-TKI resistance refractory meningeal metastasis. From November 1, 2020 to November 1 2022, a total of 10 patients were enrolled in the study, and all patients underwent NGS and CEA testing of cerebrospinal fluid. The patients had entered the stage of symptomatic and supportive treatment before intrathecal pemetrexed, experienced EGFR-TKI resistance, systemic intravenous chemotherapy and bevacizumab treatment previously. Intrathecal pemetrexed was well-effective and tolerated, occurring at the 20mg or 40mg once a week dose. The disease control rate of intrathecal injection was 88.8% (8/9); 10% (1/10) had negative cerebrospinal fluid cytology; concurrently, the quality of life (QoL)score improved, and cerebrospinal fluid CEA decreased. The median PFS of intrathecal injection was five months, and the median OS was 8.15 months. Ninety percent of patients experienced adverse events of varying degrees, with nausea, vomiting, and myelosuppression being the most common. The incidence of grade three or higher adverse events was 40% (4/10), primarily myelosuppression, which improved after systemic treatment; no treatment-related deaths occurred.This study suggests intrathecal pemetrexed can be used for salvage treatment of refractory meningeal metastatic in EGFR-TKI resistant lung adenocarcinoma.
RETRACTED: Magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair
Authors: nie xiaojing , Shi Yonghua , Wang Lei , Abudureheman Wumidan , Yang Jingxin , Lin Chen
Published: December 2023

The authors have requested that this preprint be removed from Research Square.
RETRACTED: Comparative Outcomes Between Three Different Techniques in the Fixation of Ulnar Styloid Fractures
Authors: Acar Barış , Orman Osman , Baydar Mehmet , Uzun Baki Avşar , Oruç Sevinç Ödül
Published: December 2023

The authors have requested that this preprint be removed from Research Square.
Inborn Errors of Immunity in Jordan: first report from a tertiary referral center
Authors: Alzyoud Raed , Al-Suwaiti Motasem , Maitah Hiba , Aladaileh Boshra , Noubani Mohammed , Nsour Hamazh
Published: December 2023

Purpose
Inborn errors of immunity (IEI) are a heterogeneous group of diseases with variable clinical phenotypes. Without the IEI national registry, this study has been conducted to describe the epidemiology, clinical presentations, treatment, and outcome of IEI in Jordanian children.
Methods
Retrospective data analysis for IEI children diagnosed and followed in Immunology, Allergy, and Rheumatology Division Queen Rania Children's Hospital, the only pediatric hospital in Jordan from 2010 till the end of 2022.
Results
A total of 467 patients, 263 (56.3%) males and 204 (43.7%) females, were diagnosed with IEI. The prevalence of IEI was 16.2/100,000 Jordanian children. The mean age at symptom onset was 18 months (1 week to 144 months), a positive family history was reported in 43.5%, and the consanguinity rate was 47.9%. The most common IEI category was immunodeficiencies affecting cellular and humoral immunity at 33.2%, followed by predominantly antibody deficiencies (PAD) at 16.9%. The overall IEI diagnostic delay mean (range) was 12.6 (0-135) months. Pulmonary and gastrointestinal clinical features were the most common at 55.2% and 45.6%, respectively; the majority were infection-related. The overall mortality was 33.2%; the highest rate was reported in severe combined immunodeficiency (SCID) at 56.2%
Conclusions
The high minimal estimated IEI prevalence at 16.2/100,000 Jordanian children compared to the regional and worldwide data, with the diversities in clinical presentation and distribution of IEI categories in our cohort point to unique features of IEI in Jordanian children, heeding national registry establishment, regional and international collaborative networks.
Methodology for Biomarker Discovery with Reproducibility in Microbiome Data using Machine Learning
Authors: Rojas-Velazquez David , Kidwai Sarah , Kraneveld Aletta D. , Tonda Alberto , Oberski Daniel , Garssen Johan , Lopez-Rincon Alejandro
Published: December 2023

Background: In recent years, human microbiome studies have receivedincreasing attention as this field is considered a potential source for clinicalapplications. With the advancements in omics technologies and AI, researchfocused on the discovery for potential biomarkers in the human microbime usingmachine learning tools has produced positive outcomes. Despite the promisingresults, several issues can still be found in these studies such as datasets withsmall number of samples, inconsistent results, lack of uniform processing andmethodologies, and other additional factors lead to lack of reproducibility inbiomedical research. In this work, we propose a methodology that combines theDADA2 pipeline for 16s rRNA sequences processing and the Recursive EnsembleFeature Selection (REFS) in multiple datasets to increase reproducibility andobtain robust and reliable results in biomedical research.
Results: Three experiments were performed analysing microbiome data frompatients/cases in Inflammatory Bowel Disease (IBD), Autism Spectrum Disorder(ASD), and Type 2 Diabetes (T2D). In each experiment, we found a biomarkersignature in one dataset and applied to 2 other as further validation. Theeffectiveness of the proposed methodology was compared with other featureselection methods such as K-Best with F-score and random selection as a baseline. The Area Under the Curve (AUC) was employed as a measure of diagnosticaccuracy and used as a metric for comparing the results of the proposedmethodology with other feature selection methods.
Conclusions: We developed a methodology for reproducible biomarker discoveryfor 16s rRNA microbiome sequence analysis, addressing the issues related withdata dimensionality, inconsistent results and validation across independentdatasets. The findings from the three experiments, across 9 different datasets,show that the proposed methodology achieved higher accuracy compared toother feature selection methods. This methodology is a first approach to increasereproducibility, to provide robust and reliable results.
Applying Narrative Medicine to Prepare Empathetic Healthcare Providers in Undergraduate Pharmacy Education in Singapore: A Mixed Methods Study
Authors: Han Zhe , Barton Keith C. , Ho Li-Ching , Yap Kai Zhen , Tan Doreen Su-Yin , Lee Shuh Shing , Neo Constance Xue Rui , Tan Amanda Han Lin , Boey Brian Ming Yao , Soon Charis Jia Yan , Gallagher Paul J.
Published: December 2023

Background: Although narrative medicine has demonstrated positive impact on learners’ empathy in medical education, this pedagogical approach has not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in undergraduate pharmacy students.
Methods: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N=31) and the remaining first-year cohort formed the control group (N=112). Group interviews (GIs) assessed pharmacy students’ engagement with the narrative medicine approach, their emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. Pharmacy students’ empathy was measured using Jefferson Scale of Empathy – Health Professions Student (JSE-HPS).
Results: Five themes, guided by internal and external factors in cognition, emerged from GIs: 1) incongruence between students’ motivation and faculty’s perception, 2) learning context, 3) academic context, 4) cognitive system, and 5) affective system. Themes 1, 4 and 5 referred to internal factors such as students’ motivation, perceiving learnings and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content and facilitation. There was no significant difference in JSE-HPS scores between intervention and control groups across 3 timepoints.
Conclusion: Pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients’ perspectives. The narrative medicine approach needs to be repeated and scaffolded within the curriculum to bring about meaningful and sustained improvements in empathy.
Pyk2 Tyrosine Kinase Facilitates Porphyromonas gingivalis Internalization and Autophagy in Immortalized Human Gingival Epithelial Cells
Authors: Zhang Manman , Lu Xiaoying , Wu Ximing , Yu Yang , Ma Jiaojiao , Long Xu , Xu Mengqi , Liu Jie , Pan Yaping , Kou Yurong
Published: December 2023

Background: Porphyromonas gingivalis (P. gingivalis), the keystone bacterial pathogen of chronic periodontitis, were able to invade immortalized human gingival epithelial cells (HGECs) and elicit a series of inflammatory responses. Proline-rich tyrosine kinase2 (Pyk2), a member of the focal adhesion kinase (FAK) family as non-receptor tyrosine kinase was universally acknowledged to be closely related to cell adhesion, migration and proliferation.
Methods and methods: Epi-4 cells were infected by P. gingivalis ATCC 33277 (MOI = 100). P. gingivalis internalization and cellular autophagy were evaluated by transmission electron and scanning electron microscopy. Light chain (LC) 3 Ⅱ and Pyk2 protein expression was assessed in the epi-4 cells by immunocytochemistry and immunofluorescence. LC3 Ⅱ and Pyk2 mRNA and protein expression in P. gingivalis-infected epi4 cells were measured in the absence or presence of Pyk2 inhibitor (TAE226) using real-time PCR and western blotting. The number of intracellular P. gingivalis was determined by the antibiotic protection assay.
Results: Our results demonstrated that P. gingivalis internalization induced autophagosomes in epi-4 cells. The enhanced levels of autophagy and Pyk2 expression by P. gingivalis were time-dependent. Furthermore, Pyk2 could regulate P. gingivalis internalization and autophagy. Pretreatment with TAE226 prevented these infection-induced changes in epi-4 cells.
Conclusion:Pyk2 tyrosine kinase could facilitate P. gingivalis internalization and autophagy in epi-4 cells. This study further elucidated the mechanism of P. gingivalis pathogenesis and provided new perspectives and targets for treating and preventing periodontitis.
Anxiety matters: food exposure, weight exposure, and virtual body exposure in anorexia nervosa
Authors: Melles Hanna , Jansen Anita
Published: December 2023

Background
Anxiety is a core characteristic of anorexia nervosa and a target of exposure therapy, which can be optimized if we know more about the emotional and behavioral responses during exposure to anorexia nervosa relevant fear stimuli.
Methods
We exposed patients with anorexia nervosa and healthy controls to anorexia nervosa related fear stimuli (food, eating, weighing, and various virtual bodies) in the laboratory, and tested whether the responses of patients changed after exposure treatment.
Results
Patients reported more anxiety, consumed less calories, and also reacted more negatively while imagining that virtual bodies of different weights were theirs than did healthy controls. After exposure treatment, patients reported less fears and they consumed more calories while their BMI had increased. They were also more accepting of healthier weights.
Conclusions
Exposure to food-, body- and weight-related stimuli in the laboratory induces emotional reactions in patients with anorexia nervosa that can be targeted during exposure therapy. Exposure therapy led to symptom reduction and is a promising intervention for the treatment of anorectic fears, but more research is needed to optimize its efficacy.
Proximate and Anti -Nutritional Properties of Four Forms ofthegenusBasella (Basellaceae) in South-western, Nigeria
Authors: Ojo Funmilola Mabel , Adenegan-Alakinde Taiwo Ayomipo
Published: December 2023

Background
Three species and a land race of the Genus Basella Linn. namely; Basella alba, Basella cordifolia, Basella rubra and Basella alba round exist in Nigeria. All the members are consumed as leafy vegetables. The aim of this study is to find out which of the Basella forms is more nutritious and the levels of the ant-nutritional components. Results from this study will add to our knowledge of the Basella species and also form the basis for recommendations to be made to farmers on the species to increase its cultivation and consumption.
Methods
They were evaluated for the percentage proximate, Vitamins and anti-nutritional properties using Standard methods of the Association of Official Analytical Chemists.
Results
The concentrations of the proximate, anti-nutritional and vitamin constituents varied among the species and the land race. B. alba had the highest moisture (98.00 ± 0.01%), crude fibre (0.59 ± 1.01%) and Ash (33.39 ± 2.11%) contents. B. rubra had the highest protein (3.64 ± 0.01%) and Vitamin E (0.50 ± 0.02%). B. cordifolia had the highest fat content (0.68 ± 1.03%). the species had Vitamin B1 content (2.00 ± 0.02%) except B. alba round (1.50 ± 0.02%). The percentage of proximate, Vitamins B2 and E contents were within required limits and are excellent sources of Vitamins.
Conclusion
The anti-nutrients were within the safe limits. Cyanide and Mercury were not detected in all the forms. All the vegetables can be planted and consumed depending on the need of the consumers.
Youth not engaged in education, employment, or training: A discrete choice experiment of service preferences in Canada
Authors: Quinlan-Davidson Meaghen , Dixon Mahalia , Chinnery Gina , Hawke Lisa D. , Iyer Srividya , Moxness Katherine , Prebeg Matthew , Thabane Lehana , Henderson JL
Published: December 2023

Background. Prior research has showed the importance of providing integrated support services to prevent and reduce youth not in education, employment, or training (NEET) related challenges. There is limited evidence on NEET youth’s perspectives and preferences for employment, education, and training services. The objective of this study was to identify employment, education and training service preferences of NEET youth. We acknowledge the deficit-based lens associated with the term NEET and use ‘upcoming youth’ to refer to this population group.
Methods. Canadian youth (14-29 years) who reported Upcoming status or at-risk of Upcoming status were recruited to the study. We used a discrete choice experiment (DCE) survey, which included ten attributes with three levels each indicating service characteristics. Sawtooth software was used to design and administer the DCE. Participants also provided demographic information and completed the Global Appraisal of Individual Needs–Short Screener. We analyzed the data using hierarchical Bayesian methods to determine service attribute importance and latent class analyses to identify groups of participants with similar service preferences.
Results. A total of n=503 youth participated in the study. 51% of participants were 24-29 years of age; 18.71% identified as having Upcoming status; 41.15% were from rural areas; and 36.03% of youth stated that they met basic needs with a little left. Participants strongly preferred services that promoted life skills, mentorship, basic income, and securing a work or educational placement. Three latent classes were identified and included: (i) job and educational services (38.9%), or services that include career counseling and securing a work or educational placement
(ii) mental health and wellness services (34.9%), or services that offer support for mental health and wellness in the workplace and free mental health and substance use services; and (iii) holistic skills building services (26.1%), or services that endorsed skills for school and job success, and life skills.
Conclusions. This study identified employment, education, and training service preferences among Upcoming youth. The findings indicate a need to create a service model that supports holistic skills building, mental health and wellness, and long-term school and job opportunities.