bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term ex-vivo normothermic perfusion of human split livers: a unique model to study new therapeutics and increase the number of available organs
Authors: Lau Ngee-Soon , Ly Mark , Dennis Claude , Jacques Andrew , Cabanes-Creus Marti , Toomath Shamus , Huang Joanna , Mestrovic Nicole , Yousif Paul , Chanda Sumon , Wang Chuanmin , Lisowski Leszek , Liu Ken , Kench James , McCaughan Geoffrey , Crawford Michael , Pulitano Carlo
Published: March 2023

Current perfusion technology only allows livers to be preserved ex-vivo for short periods. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed develop a long-term model of ex-vivo perfusion including a surgical split and simultaneous perfusion of both partial grafts. Our long-term perfusion system included long-term oxygenators, a gas-mixer and a dialysis filter. Human livers declined for transplantation were perfused using a red-cell based perfusate under normothermic conditions (36°C) and then split and simultaneously perfused on separate machines. Ten human livers were split resulting in 20 partial grafts. The median ex-vivo survival was 165 hours (7 days). Long-term graft survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. The grafts that survived > 7 days demonstrated significantly higher bile production, Factor-V production, and hepatic arterial flow and significantly lower microvesicular steatosis. We report reliable long-term ex-vivo perfusion of human livers and demonstrate the ability to split and perfuse these organs using a reproducible protocol. This provides the opportunity for improved assessment of organs and could act as a model for the testing of therapeutics with a matched control.
Effect of Traditional Chinese Medicine Combined Group Psychotherapy on Psychological Distress Management and Gut Micro-biome Regulation for Colorectal Cancer Survivors: A Single-arm Phase I Clinical Trial
Authors: Sun Lingyun , Pang Ying , Wang Zixu , Liu Jiaxi , Peng Rongyan , Yan Yunzi , Yang Yufei , Tang Lili
Published: March 2023

Objective: To evaluate the efficacy and feasibility of utilizing Traditional Chinese Medicine(TCM) combined group psychotherapy intervention on psychological distress management and gut micro-biome regulation for colorectal(CRC) survivors.
Methods: A single-arm phase I clinical trial was conducted between December 2020 and December 2021 in Xiyuan and Beijing Cancer Hospital in China. Inclusion criteria was stage I-III CRC survivors after radical surgery with age between 18-75. The intervention was a six-week online TCM combined group psychotherapy intervention including 90 minutes’ communication, TCM lifestyle coaching, self-acupressure guidance and mindfulness practice led by TCM oncologist and psychiatrist each week. Outcomes were measured by Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Fear of Cancer Recurrence Inventor (FCRI), and Quality of Life Questionnaire(QLQ-C30). Fetal samples before and after intervention were collected for 16Sr RNA analysis.
Results: We recruited 40 CRC survivors and 38 of them finally completed all interventions with average age of 58±13 years’ old. Paired t-test showed that SAS at week 2(35.4±5.8), week 4(37.9±10.5) and week 6(31.3±6.4) during the intervention was significantly lower than baseline (42.1±8.3, p<0.05 respectively). SDS score also declined substantially from baseline (38.8±10.7) to week 2(28.3±8.8, p<0.001) and week 6(25.4±7.7, p<0.001). FCRI decreased from 19.4±7.2 at baseline to 17.5±7.1 at week 4(p=0.038) and 16.3±5.8 at week 6(p=0.008). Although changes of QLQ-C30 were not statistically prominent, insomnia and fatigue significantly alleviated. The abundances of gut microbiota Intestinibacter, Terrisporobacter, Coprobacter and Gordonibacter were all significantly elevated after intervention.
Conclusions: TCM combined group psychotherapy intervention is feasible and effective to reduce CRC survivors’ psychological distress and modulate certain gut bacteria which might be associated with brain-gut axis effect. It is necessary to carry out with phase II randomized controlled clinical trial.
2D and 3D territories and territory overlap of Willow Warblers Phylloscopus trochilus in Arctic forests
Authors: Matantseva Maria V. , Simonov Sergey A.
Published: March 2023

Space use by animals is usually considered in two horizontal dimensions, less often with a separate analysis of the vertical stratification. Only recently, studies on three-dimensional (3D) space use appeared with modelling of individual movements simultaneously in three dimensions. In ornithology, such works were done when studying home ranges of large birds tagged with radio transmitters and GPS locators or during visual observations of colour-banded passerine wintering birds and residents in tropics. To our knowledge, such methods have not been used for studying 3D territories advertised by singing in passerines during the breeding period in the Palearctic Region. We studied the 3D territoriality of Willow Warblers Phylloscopus trochilus during the breeding period in the Kola Peninsula, Arctic Region, NW Russia. Using the method of Cooper et al. (2014), we located points with 3D coordinates at which individually marked males sang and analysed 2D and 3D territories and their overlap in R. We found that 2D methods, compared to 3D methods, overestimated individual spatial overlap by 8.5% and total spatial overlap by 16.7%. Thus, Willow Warblers in Arctic forests can partition their territorial space in 3 dimensions. With the overlap indices adopted for use with 3D data, we also proved that they could avoid areas of overlap. Furthermore, it was demonstrated for the first time that the overestimation of the territory overlaps by 2D versus 3D methods grew higher as the number of neighbour territories increased. In dense populations, 3D territories are arranged like layers of roof tiles, avoiding substantial overlaps.
Assessing receptive verb knowledge in late talkers and autistic children: Advances and cautionary tales
Authors: Horvath Sabrina , Arunachalam Sudha
Published: March 2023

Purpose
Using eye-tracking, we assessed the receptive verb vocabularies of late talkers and typically developing children (Experiment 1) and autistic preschoolers (Experiment 2). We evaluated how many verbs participants knew and how quickly they processed the linguistic prompt.
Method
Participants previewed two dynamic scenes side-by-side (e.g., “stretching” and “clapping”) and were then prompted to find the target verb. Children’s eye gaze behaviors were operationalized using established approaches in the field with modifications in consideration for the type of stimuli (dynamic scenes versus static images) and the populations included. Accuracy was calculated as a proportion of time spent looking to the target, and linguistic processing was operationalized as latency of children’s first look to the target.
Results
In Experiment 1, there were no group differences in the proportion of verbs known, but late talkers required longer to demonstrate their knowledge than typically developing children. Latency was predicted by age but not language abilities. In Experiment 2, autistic children’s accuracy and latency were both predicted by receptive language abilities.
Conclusion
Eye gaze can be used to assess receptive verb vocabulary in a variety of populations, but in operationalizing gaze behavior, we must account for between- and within-group differences. Bootstrapped cluster-permutation analysis is one way to create individualized measures of children’s gaze behavior, but more research is warranted using an individual differences approach with this type of analysis. Finally, latency may not be a valid measure for dynamic scene stimuli for children under three years old.
V-I penoscrotal reconfiguration: a simple new technique in the treatment of congenital webbed penis.
Authors: Bagnara Vincenzo , Berrettini Alfredo , Castagnetti Marco , Messina Mario , Angotti Rossella , Paraboschi Irene , Donà Anna Diletta
Published: March 2023

Introduction: Congenital webbed penis (CWP) describes a condition in which the ventral skin of the penis is fused with the median raphe of the scrotum, thereby obscuring the penoscrotal angle.
Materials and methods: We retrospectively reviewed the clinical notes of 21 patients undergoing treatment of CWP with “V-I penoscrotal reconfiguration technique”. CWP was assessed according to the classification of El-Koutby which includes Grade 1: the webbed skin reaches the proximal 1/3 of the penile shaft; Grade 2: the webbed skin extends to the mid 1/3 of the penis; Grade 3: the web extends to the distal 1/3 of the shaft. If phimosis was associated, this was graded according to Meuli’s classification into 4 degrees. The degree of parental satisfaction was quantified in 5 degrees according to the Likert Scale: “very unsatisfied”: score 0; “unsatisfied”: score 1; “neither satisfied nor unsatisfied”: score 2; “satisfied”: score 3; “very satisfied”: score 4.
Results: CWP was grade 3 in 11 patients (52%), grade 2 in 5 patients (24%), and grade 1 in 5 patients (24%). Furthermore, it was present as isolated malformation (5 cases, 24%), associated with phimosis (11 cases, 52%), associated with hypospadias (3 cases, 14%), associated with hypospadias and phimosis (2 cases, 10%). Post-operative follow-up included clinical assessments at 2 weeks and then at 1, 6, and 12 months. No postoperative complications were noted during the follow-up. Even the one-year follow-up did not show any blemishes or scar retractions with penile curvature. In no case was necessary a reoperation. The aesthetic result was excellent in all cases. Regarding the parental satisfaction score in 17 cases parents reported a score of 4 and the remaining 4 a score of 3, especially for the aspect of the circumcised penis.
Conclusions: The webbed penis is an infrequent congenital malformation, which causes psychological distress, especially in parents. Additionally, possible functional problems may arise during sexual activity in adulthood. Its correction in pediatric age is therefore desirable, to prevent possible psychological and sexual. In our opinion, the described “V-I reconfiguration technique” is simple to perform, and easy to reproduce with excellent aesthetic and functional results.
Image fusion guidance for left subclavian artery in situ fenestration during thoracic endovascular repair
Authors: Zhao Liang , Liu Jidong , Cai Xiaoshu , Yang Wengang , Wang Ji
Published: March 2023

Objectives
To evaluate the feasibility and clinical benefit of utilizing image fusion for thoracic endovascular repair (TEVAR) with in situ fenestration (ISF-TEVAR).
Materials and methods
Between January 2020 and December 2020, we prospectively collected 18 consecutive cases with complex thoracic aortic lesions who underwent image fusion guided ISF-TEVAR. As a control group, 18 patients were collected from historical medical records from June 2019 to December 2019. The fusion group involved the use of 3D fusion of CTA and fluoroscopic images for real-time 3D guidance, and the control group involved the use of only regular fluoroscopic images for guidance. The total contrast medium volume, hand-injected contrast medium volume, overall operative time, radiation dose and fluoroscopy time were compared between the two groups. Accuracy was measured based on preoperative CTA and intraoperative digital subtraction angiography.
Results
3D fusion imaging guidance was successfully implemented in all patients in the fusion group. Hand-injected contrast medium volume and overall operative time were significantly lower in the fusion group than in the control group (p =.028 and p =.011). Compared with the control group, the fusion group showed a significant reduction in time and radiation dose-area product (DAP) for fluoroscopy (p=.004 and p =.010). No significant differences in total radiation dose (DAP) or total contrast medium volume were observed (p =.079 and p=.443). Full accuracy was achieved in 8 cases (44%), with a mean deviation of 2.61 mm ± 3.1 (range 0.0-8.4 mm).
Conclusions
3D image fusion for ISF-TEVAR was associated with a significant reduction in hand-injected contrast medium, time and radiation exposure for fluoroscopy and overall operative time. The image fusion guidance showed potential clinical benefits towards improved treatment safety and accuracy for complex thoracic endovascular interventions.
Isolation and functional characterization of three TERMINAL FLOWER 1-like genes from Platanus acerifolia
Authors: Zhang Sisi , Zhou Qin , Yang Xingyu , Wang Jianqiang , Jiang Jie , Sun Miaomiao , Liu Yanjun , Nie Chaoren , Bao Manzhu , Liu Guofeng
Published: March 2023

Three TERMINAL FLOWER 1 (TFL1)-like genes were isolated and characterized from London plane tree (Platanus acerifolia). All genes have conserved genomic organization and characteristic of the phosphatidylethanolamine-binding protein (PEBP) family. Sequence alignment and phylogenetic analysis indicated that two genes belong to the TFL1 clade, designated as PlacTFL1a and PlacTFL1b, while another one was grouped in the BFT clade, named as PlacBFT. qRT-PCR analysis showed that all three genes primarily expressed in vegetative phase, but the expression of PlacTFL1a was much higher and wider than that of PlacTFL1b, with the latter only detected at relatively low expression levels in apical and lateral buds in April. PlacBFT was mainly expressed in young stems of adult trees followed by juvenile tissues. Ectopic expression of any TFL1-like gene in Arabidopsis showed phenotypes of delayed or repressed flowering. Furthermore, overexpression of PlacTFL1a gene in petunia also resulted in extremely delayed flowering. In non-flowering 35:PlacTFL1a transgenic petunia plants, the FT-like gene (PhFT) gene was significantly up-regulated and AP1 homologues PFG, FBP26 and FBP29 were significantly down-regulated. Yeast two-hybrid analysis indicated that only weak interactions were detected between PlacTFL1a and PlacFDL, and PlacTFL1a showed no interaction with PhFDL1/2. These results indicated that the TFL1-like genes of Platanus have conserved roles in repressing flowering, but probably via a distinct regulatory mechanism.
Profiling of differentially expressed circulating exosomal microRNAs among patients with coronary artery disease
Authors: Hao Wen-Rui , Hong Hong-Jye , Cheng Chun-Yao , Cheng Tzu-Hurng , Liu Ju-Chi , Wang Yi-Chih , Chen Jin-Jer
Published: March 2023

Coronary artery disease (CAD) is the leading cause of death in developed countries. Studies have indicated that ischemic tissues may release exosome-carried microRNAs (miRNAs) into circulation. miRNAs are a class of small, endogenous, noncoding RNAs that regulate the expression of multiple target genes at the posttranscriptional level on the basis of sequences that are complementary to target mRNA molecules. However, the prognostic role of exosomal miRNAs in CAD remains unclear. In this study, we compared the profiles of circulating exosomal miRNA expression in patients with angiographically assessed absent and well-developed collateral vessels. A total of 109 patients who underwent coronary angiography were recruited, including 31 patients with CAD and well-developed collateral circulation, 44 patients with no collateral flow (as indicated by their Rentrop scores), and 34 patients with patent coronary arteries (control group). miRNAs were then extracted from exosomes collected from peripheral blood and amplified, and a miRNA microarray system was used to profile the expression of these miRNAs in the exosomes. Subsequently, the effects of specific miRNAs on angiogenesis were identified in vitro. On the basis of the array data, miRNAs with high differential expression ratios along with Grade 0–2 collateral flow were selected. Among patients with adequate collateral perfusion, the top five overexpressed candidate miRNA markers were miR-29a, miR-592, miR-518e, miR-32, and miR-766. Similarly, among patients with no collateral flow, the top five overexpressed miRNAs were miR-300, miR-576-3p, miR-642, miR-620, and miR-1255a. As a next step, the angiogenic ability and proangiogenic signaling pathway of two specific angiogenesis-related miRNAs (i.e., miR-300 and miR-29a) with high differential expression ratios were determined. According to the microarray data and study results, miRNAs with high expression levels can be used as biomarkers to distinguish between types of collateral circulation in patients with CAD and can be used in diagnostic or prognostic applications for high-risk patients with CAD. These findings may serve as a reference for the development of noninvasive and cost-effective approaches aimed at identifying the high risk of CAD and for the development of novel therapeutic targets for vascular diseases, including CAD with impaired collateral angiogenesis.
Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment
Authors: Yin Zhaowei , Pan Shaowei , Shi Chen , Wu Guanfu , Feng Yan , Qin Chaoren , Zhang Jing , Yu Ziyi , Liang Bin , Gui Jianchao
Published: March 2023

Adipose derived stem cells (ADSCs) have the potential to attenuate osteoarthritis (OA); however, complications such as immune rejection and tumour formation limit their application. Exosomes (Exos)-mediated acellular therapy is promising in alleviating OA. This study aims to confirm whether ADSC-exos derived from infrapatellar fat pad (IPFP, ExosIPFP) are more suitable for ameliorating OA than ADSC-exos derived from subcutaneous fat (ScAT, ExoScAT) in vitro and in DMM models. Then, we investigated the regulatory mechanism by which the two kinds of Exos inhibit extracellular matrix (ECM) degradation in OA. ADSCs were successfully isolated and Exos were then obtained. ExosIPFP exhibited better attenuated effects on osteoarthritic chondrocytes in vitro and in vivo than ExoScAT. Small RNA sequencing was performed and the results shown that miR-99b-3p was upregulated in ExosIPFP. In vitro experiments confirmed that ADAMTS4 is a direct downstream target of miR-99b-3p. Over-expression miR-99b-3p in ExosScAT (ExosScAT-99b-3p) indicated that miR-99b-3p serves a positive role for OA treatment by inhibiting ADAMTS4 expression both in vitro and in vivo. In addition, hydrogel microparticles (HMPs) system was prepared by microfluidic technology, and confirmed the beneficial results for long-term therapeutic by continuous release of Exos. Take together, these results suggest that the therapeutic effects of ADSC-Exos may vary according to differential expression of miRNAs. Exosomal miR-99b-3p may act as a promising therapeutic strategy for OA, in addition, the injectable HMPs act as a sustained local drug release system, therefore representing great potential for treating OA and other diseases.
Bone Marrow Mesenchymal Stem Cell-Derived Exosomes and Exosome-Liposome Hybrids as Nanocarriers for Delivering Cas9-GFP Plasmid to Embryonic Kidney Cells
Authors: Gharehchelou Behnaz , Mehrarya Mehrnoush , Vosough Massoud , Arjmand Sareh , Uskoković Vuk , Siadat Seyed Omid Ranaei , Karima Saeed , Sefidbakht Yahya
Published: March 2023

Exosomes are natural membrane-enclosed nanovesicles (30–150 nm) involved in cell-cell communication. Recently, they have garnered considerable interest as nanocarriers for the controlled transfer of therapeutic agents to cells. Here, exosomes were derived from bone marrow mesenchymal stem cells (BM-MSCs) using three different isolation methods, and the size exclusion chromatography (SEC) led to the isolation with the highest purity. The limitation of using pure exosomes for encapsulating large nucleic acids was then addressed by the development of exosome-liposome hybrids. The efficiency of these hybrids to transfer the Cas9-green fluorescent protein plasmid (pCas9-GFP) into the human embryonic kidney 293T (HEK293T) cells were evaluated compared to the pure exosomes. The method of combining exosomes with liposomes (freeze-thaw vs. direct mixing) was proved to be more decisive in determining the size of the vesicular hybrids. In contrast, the ionic nature of the liposomes (lipoplex vs. cationic) in these hybrids was proved to be more important in determining the transfection efficiency. Both Cas9-GFP-loaded exosomes and exosome-liposome hybrids were taken up well by the HEK293T and were able to transfect them with their plasmid loads; however, the pure exosome and then the vesicular hybrids incorporating lipoplex transfected the cells more efficiently than those containing cationic liposomes.
Invasive pancreatic cystic neoplasm with favorable prognosis: A large retrospective cohort study over two decades
Authors: song yanjing , li zhe , Cui Hongyuan , xu jingyong , Song Jinghai
Published: March 2023

Purposes: Invasive pancreatic cystic neoplasms (iPCNs) are an uncommon and biologically heterogeneous group of aggressive neoplasms. We aimed to investigate the clinicopathological characteristics of iPCN patients, and to develop nomograms for individual survival prediction after radical surgery. Methods: Data of patients diagnosed with iPCN between 2000 and 2018 from the SEER database were retrieved. The differences of clinical outcomes were evaluated using Kaplan-Meier analysis. Nomograms were proposed based on Cox regression model and internally validated by C-index, AUC value, and calibration plot. Results: A total of 7777 iPCN patients were enrolled. Most neoplasms were advanced, with 63.1% at stage IV. The 3-year OS and CSS rates in surgical patients were as follows: 45.7% and 50.1% for invasive IPMN, 54.8% and 59.3% for invasive MCN, 97.8% and 98.2% for invasive SPN, 88.9% and 88.9% for invasive SCN. Subgroup analyses showed no clinical benefit from chemotherapy or radiotherapy in lymph node-negative iPCN patients who underwent surgery. The following variables associated with OS and CSS were identified: age, race, chemotherapy, radiotherapy, histologic type, pathological grade, regional nodes examined, and T, N, and M stage. The nomograms had good discrimination and calibration by internal validation, with AUC value of 0.800 for 3-year OS and 0.814 for 3-year CSS. Conclusion: Our study showed that the prognosis of iPCN patients was significantly better than PDAC patients. The proposed nomograms demonstrated substantially better discrimination and calibration.
ACE2 (angiotensin converting enzyme) polymorphisms and susceptibility of severe SARS- CoV-2 in subset of Pakistani population
Authors: Sidhwani Santosh Kumar , Mirza Talat , Khatoon Ambrina , Shaikh Fouzia , Khan Rizma , Shaikh Omer Ahmed , Nashwan Abdulqadir J.
Published: March 2023

Science is digging for the varied presentation of COVID-19 patients exposed to the same risk factors, and medical conditions may be influenced by the presence of polymorphic genetic variants. This study investigated the link between ACE2 gene polymorphisms and the severity of SARS-Cov-2. This cross-sectional study recruited COVID-19 PCR-positive patients by consecutive sampling from Ziauddin Hospital from April to September 2020. DNA was extracted from whole blood, followed by gene amplification and Sanger’s sequencing. Most of the patients, 77: 53.8%, were serious. Males were higher (80; 55.9%) with age more than 50 years (106: 74.1%). We found 22 ACE2 SNPs rs2285666 SNP most prevalent with 49.2% CC, 45.2% TT, 4.8% CT heterozygosity, and 0.8% AA genotypes. Variants with multiple genotypes were also insignificantly associated with the severity of COVID-19 in the analysis of the dominant model. Only rs2285666 had a significant statistical link with gender (p-value 0.034, OR; 1.438, CI; 1.028-2.011) while rs768883316 with age groups (p-value 0.026, OR; 1.953, CI; 1.085-3.514). Haplotypes ATC of three polymorphisms (rs560997634, rs201159862, and rs751170930) commonly found in 120 (69.77%) and TTTGTAGTTAGTA haplotype consisting of 13 polymorphisms (rs756737634, rs146991645, rs1601703288, rs1927830489, rs1927831624, rs764947941, rs752242172, rs73195521, rs781378335, rs756597390, rs780478736, rs148006212, rs768583671) in 112 (90.32%) had statistically significant association with the severity having p=value 0.029 and 0.001 respectively. Males of old age and diabetics are found to have more severe COVID-19 infection in the current study. We also found that common ACE2 polymorphism rs2285666 influences the susceptibility of acquiring the severe SARS-CoV-2 infection.
Cerebrospinal fluid leakage prevention using the anterior transpetrosal approach with versus without postoperative spinal drainage: an institutional cohort study
Authors: Adachi Kazuhide , Hasegawa Mitsuhiro , Hirose Yuichi
Published: March 2023

The efficacy of spinal drain (SD) placement for cerebrospinal fluid (CSF) leakage prevention after anterior transpetrosal approach (ATPA) remains unclear. Thus, we aimed to assess whether postoperative SD placement improved postoperative CSF leakage after a skull base reconstruction procedure using a small abdominal fat and pericranial flap and clarify whether bed rest with postoperative SD placement increased the length of hospital stay. This retrospective cohort study included 48 patients who underwent primary surgery using ATPA between November 2011 and February 2022. First, we evaluated the necessity of SD placement for CSF leakage prevention by comparing the routine SD placement period to a period in which the SD was removed immediately after surgery. Second, the effects of different SD placement durations were evaluated to understand the adverse effects of SD placement requiring bed rest. No patient with or without SD placement developed CSF leakage. The median postoperative time to first ambulation was 3 days shorter (P < 0.05) and the length of hospital stay was 7 days shorter (P < 0.05) for patients who underwent SD removal immediately after surgery (2 and 12 days, respectively) than for those who underwent SD removal on postoperative day 1 (5 and 19 days, respectively). This skull base reconstruction technique was effective in preventing CSF leakage in patients undergoing ATPA, and postoperative SD placement was not necessary. Removing the SD immediately after surgery can lead to earlier postoperative ambulation and shorter hospital stay by reducing medical complications and improving functional capacity.
Investigating the Correlation between Genetic and Biochemical Markers in Multiple Sclerosis
Authors: Borisovs Vitalijs , Trapina Ilva , Paramonova Natalia , Sjakste Nikolajs
Published: March 2023

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with a complex etiology involving genetic and environmental factors. Genome-wide association studies have identified several genetic variants associated with MS susceptibility, including the XRCC1 gene involved in DNA base excision repair. Environmental factors such as exposure to nitric oxide have also been linked to MS development and progression. This study aims to investigate the potential association between these factors, including patient demographic descriptors and biochemical markers, to better understand the mechanisms underlying MS. This scientific article discusses the results of statistical analysis of biomarkers in relation to multiple sclerosis (MS). Our findings reveal significant associations between various factors, such as levels of nitric oxide (NO) and serum nitrite levels, NO and plasma malondialdehyde (MDA) levels, nitrite and nitrate levels in serum, and nitrite and MDA levels in plasma. It also suggests a potential association between XRCC1 rs25487 T > C locus deviation from Hardy-Weinberg equilibrium and MS in the population of Latvia. Furthermore, XRCC1 rs25487 T > C is found to be statistically significantly associated with DNA damage in peripheral blood mononuclear cells (PBMNC) and potentially associated with levels of NO. Additionally, PARP1 rs1136410 A > G is linked to plasma levels of MS patients. Finally, the study finds that XRCC1 rs25487 T > C is associated with both plasma nitrite levels and serum malondialdehyde (MDA) levels of MS patients, with the rare allele T specifically correlated with the latter.
Another non-anthropic leporid accumulation in Southwestern Iberia? The case of a leporid sample from Morgado superior (Tomar, Portugal)
Authors: Almeida Nelson J. , Saladié Palmira , Cerrillo-Cuenca Enrique , Oosterbeek Luiz
Published: March 2023

The Morgado superior rock shelter is located near the city of Tomar, in Central Portugal. This site presents important funerary contexts that according to published information encompass the Neolithic, Chalcolithic, and Bronze Age. Other non-funerary uses are not yet characterized but were briefly suggested. A faunal sample of the 1988 and 2012 interventions is analysed from a zooarchaeological and taphonomical perspective, focusing on the leporid remains that largely dominate the assemblage. Clear indicators of a human origin are absent, while a configurational approach allows the description of exogenous and intrusive origins. The characteristics of the registered consumption taphonomical indicators are suggestive of scat and non-ingested accumulation by foxes. Furthermore, this study allows us to discuss some aspects of the formation of the stratigraphy of this important cave necropolis, while also serving as an example of the expected results of foxes’ action on leporid remains in an archaeological site.
Navigating the Maze of Global Debt: An Analysis of International Debt Statistics with PostgreSQL
Authors: Nasir Muhammad Taha , Tulkinov Shavkatjon
Published: March 2023

Countries often take on debt as a means of financing their economic development, such as funding infrastructure projects, investing in education or healthcare, or stimulating economic growth. This paper aims to analyze international debt statistics using the PostgreSQL database management system, specifically focusing on the external debt of countries as presented in the World Bank's International Debt Statistics (IDS) database. The analysis examines the most prevalent debt indicators and investigates the amount of debt owed by countries to identify potential economic issues and findings show that long-term external debt is the most common form of external debt for low- and middle-income countries. The IDS dataset displays that the most prevalent debt indicators are DT.INT.OFFT.CD, DT.INT.MLAT.CD, DT.INT.DLXF.CD, DT.AMT.OFFT.CD, DT.AMT.MLAT.CD, and DT.AMT.DLXF.CD. The study also finds that among the top five countries with the highest maximum debt, four are from emerging market economies, suggesting that they may be facing economic challenges. However, the study emphasizes that the findings should be interpreted with caution and that other economic indicators, such as the debt-to-GDP ratio and debt sustainability, should be considered when analyzing a country's overall economic health.
SNV/indel hypermutator phenotype in biallelic RAD51C variant - Fanconi anemia
Authors: Zemet Roni , Du Haowei , Gambin Tomasz , Liu Pengfei , Lupski James R , Stankiewicz Paweł
Published: March 2023

We previously reported a fetus with Fanconi anemia (FA), complementation group O due to compound heterozygous variants involving RAD51C. Interestingly, the trio exome sequencing analysis also detected eight apparent de novo mosaic variants with variant allele fraction (VAF) ranging between 11.5%-37%. Here, using whole genome sequencing and a 'home-brew' variant filtering pipeline and DeepMosaic module, we investigated the number and signature of de novo heterozygous and mosaic variants and the rare phenomenon of hypermutation. Eight-hundred-thirty apparent dnSNVs and 21 de novo indels had VAFs below 37.41% and were considered postzygotic somatic mosaic variants. The VAFs showed a bimodal distribution, with one component with an average VAF of 25% (range: 18.7-37.41%) (n=446), representing potential postzygotic first mitotic events, and the other component with an average VAF of 12.5% (range: 9.55-18.69%) (n=384), describing potential second mitotic events. No increased rate of CNV formation was observed. The mutational pattern analysis for somatic single base substitution showed SBS40, SBS5, and SBS3 as the top recognized signatures. SBS3 is a known signature associated with homologous recombination-based DNA damage repair error. Our data demonstrate that biallelic RAD51C variants show evidence for defective genomic DNA damage repair and thereby result in a hypermutator phenotype with the accumulation of postzygotic de novo mutations, at least in the prenatal period. This 'genome hypermutator phenomenon' might contribute to the observed hematological manifestations and the predisposition to tumors in patients with FA, and pregnancy loss in general. We propose that other FA groups should be investigated for genome-wide de novo variants.
Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000-2020 period
Authors: Tuli Gerdi , Munarin Jessica , Matarazzo Patrizia , Marino Antonio , Corrias Andrea , Palestini Nicola , Quaglino Francesco , De Sanctis Luisa
Published: March 2023

Purpose. To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology.
Methods. Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed.
Results. The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p=0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and high-risk class (60% and 80% respectively) (p= 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8±307.1 ng/ml) [p=0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p=0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60% and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p=0.04).
Conclusion. DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardize management and reduce disease persistence in childhood.
Surgical experience of extracorporeal membrane oxygenation for neonates with severe respiratory failure
Authors: Zhang Qi-Liang , Chen Xiu-Hua , Zhou Si-Jia , Cao Hua , Chen Qiang
Published: March 2023

Objective
Extracorporeal membrane oxygenation (ECMO) has been increasingly used for severe neonatal respiratory failure refractory to conventional treatments. This paper summarized our operation experience of neonatal ECMO via cannulation of the internal jugular vein and carotid artery.
Methods
The clinical data of 12 neonates with severe respiratory failure who underwent ECMO via internal jugular vein and carotid artery in our hospital from January 2021 to October 2022 were collected.
Results
All the neonates were successfully operation. The size of arterial intubation was 8 F, the size of venous intubation was 10 F. The operation time was 29 (22–40) minutes. ECMO was successfully removed in 8 neonates. They were successfully reconstructed the internal jugular vein and carotid artery. Arterial blood flow was unobstructed in 5 patients, mild stenosis in 2 patient, moderate stenosis in 1 patient. Venous blood flow was unobstructed in 6 patients, mild stenosis in 1 patient, and moderate stenosis in 1 patient. The complications were as follows: 1 case had poor neck incision healing after ECMO removing. No complications such as incisional bleeding, incisional infection, catheter-related blood infection, cannulation accidentally pulling away, vascular laceration, thrombosis, cerebral hemorrhage, cerebral infarction, and hemolysis occurred in all the patients.
Conclusion
Cannulation of the internal jugular vein and carotid artery can quickly establish an effective ECMO access for neonates with severe respiratory failure. Careful, skilled and delicate operation was essential. In addition, during the cannulation process, we should pay special attention to the position of cannulation, firm fixation and strict aseptic operation.
A comparative observational study on intrasphincteric injections with Botulinum toxin vs. non-invasive sacral neuromodulation in chronic refractory constipation
Authors: Walther Mona , Müller Hanna , Weiß Christel , Carbon Roman , Diez Sonja , Besendörfer Manuel
Published: March 2023

Background: Botulinum toxin injections in the anal sphincter apparatus (Botox) and non-invasive sacral neuromodulation (niSNM) are options for treatment of refractory chronic constipation. We present a retrospective comparative observational study.
Patients and Methods: From 2014 to 2022, pediatric patients with chronic constipation were either treated with Botox or niSNM with continuation of conservative treatment. Comparison was conducted regarding the primary outcome variables defecation frequency, stool consistency, and abdominal pain. Secondary outcomes were fecal incontinence, enuresis, change of medication and safety of treatment.
Results: 19 Botox patients (10 boys, 9 girls, 12 patients with Hirschsprung disease (HD), 7 patients with functional constipation (FC)) were compared to 24 niSNM patients (18 boys, 6 girls, 12 HD patients, 7 FC patients). Groups differed significantly in age (5.0 years (Botulinum toxin) and 6.5 years (niSNM), mean values, p-value 0.008). Improvement of constipation was seen in 68 % (n = 13/19) of Botox and 88 % (n = 21/24) of niSNM patients (p = 0.153). Influence of etiology on therapeutic effects was not observed. Complications were minor.
Conclusion: Botox and niSNM can be considered as valuable and effective treatment options in refractory chronic constipation. Prospective, large-population studies should be designed to enable improved evidence.
Neuritin restores auditory following cochlear spiral ganglion neuron denervation of gerbils
Authors: gui fei , Dandan Song , Haiyan Wang , Shuai Zhang , Xiaopin Sun , Yu Hong , Yi Yang , Rong Chen , Jin Huang , Xiaoming Song , Lei Yang
Published: March 2023

Spiral ganglion neurons (SGNs) transmit sound signals received by hair cells to the auditory center to produce hearing. The quantity and function are important for maintaining normal hearing function. Limited by the regenerative capacity, SGNs are unable to regenerate spontaneously after injury. Various neurotrophic factors play an important role in the regeneration process. Neuritin, a neurite outgrowth factor, is a neurotrophic factor closely related to neural plasticity. In this study, we used bioinformatics analysis to show that neuritin was negatively correlated with cochlear damage. Then, we aimed to establish a cochlear spiral ganglion-specific sensorineural deafness model in gerbils using ouabain and determine the effects of exogenous neuritin protein in protecting damaged cochlear SGNs and repairing damaged auditory nerve function. The provides a new research strategy and scientific basis for the prevention and treatment of sensorineural deafness caused by the loss of SGNs. We found that neuritin is expressed throughout the development of the gerbil cochlea, primarily in the SGNs and Corti regions. The expression of neuritin was negatively correlated with the sensorineural deafness model. In vitro and in vivo revealed that neuritin significantly maintained the number and arrangement of SGNs and nerve fibers in the damaged cochlea and effectively protected the high-frequency listening function of gerbils.
Detection of IoT Botnet using Machine learning and Deep Learning Techniques
Authors: W Regis Anne , G Kirubavathi , UK Sridevi
Published: March 2023

In recent years, there has been a proliferation of IoT (Internet of Things) devices and its enabling technologies in industries, product flow management, healthcare, transportation and other smart environments. The provision of IoT devices with IP (Internet Protocol) address allows for communication between these cyber-physical systems without any intervention. Lack of security on these end devices has led to many attacks like denial-of-service, Botnets, identity theft and data theft attacks. Mirai, Torii, Emotet, Dridex, Trickbot, Glupteba and QBots are all example of IoT vulnerabilities. Artificial intelligence enables to build strong secure cyber-physical systems. Machine learning and Deep learning techniques combats cyber-attacks by detection and prevention of these Botnets. In this paper, we explore on Botnet attacks that is prevalent in IoT devices because of lack of standards in security when manufacturing or illiteracy of security awareness by the users. Machine learning and Deep learning are prospective solutions to detect and prevent cyber intrusions on IoT devices using anomaly detection. In this paper, firstly we present a framework for Botnet detection to detect an attack on real time traffic. Secondly, we compare and contrast different machine learning and deep learning algorithms for detection of Botnets on the standard features using the Aposemat IoT-23 dataset. Among the deep learning models Gated Recurrent Unit (GRU) efficiently detects Botnets with 99.87% accuracy. Thirdly, the raw packet captured (pcap) files form Aposemat IoT-23 dataset are analyzed for attacks using Wireshark tool. Then deep learning model GRU is used to detect the malware attacks with accuracy of 99.89 and better time complexity. Finally, we compare the models based on performance metrics like accuracy, precision, recall, F1-Score and time complexity to deduce the best model on both feature based and featureless IoT traffic.
FAP expression in alpha cells of Langherhans insulae – implications for FAPI radiopharmaceuticals’ use
Authors: Kirienko Margarita , Centonze Giovanni , Sabella Giovanna , Sollai Mauro , Sollini Martina , Lan Xiaoli , Chen Haojun , Terracciano Luigi , Seregni Ettore , Milione Massimo
Published: March 2023

Purpose
Radiopharmaceuticals targeting fibroblast activation protein alpha (FAP) are increasingly studied for diagnostic and therapeutic applications. We discovered FAP expression at immunohistochemistry (IHC) in the alpha cells of the Langerhans insulae of few patients. Therefore, we planned an investigation aimed at describing FAP expression in the pancreas and discussing the implications for radioligand applications.
Methods
We retrospectively included 40 patients from 2 institutions (20 pts each) according to the following inclusion/exclusion criteria: i) pathology proven pancreatic ductal adenocarcinoma and neuroendocrine tumors (NET), 10 pts per each group at each center; ii) and availability of paraffin-embedded tissue and iii) clinical-pathological records. We performed IHC analysis and applied a semiquantitative visual scoring system (0, negative staining; 1, present in less than 30%; 2, present in more than 30% of the area). FAP expression was assessed according to histology – NET(n = 20) vs ductal adenocarcinoma(n = 20) - and to previous treatments within the adenocarcinoma group. Local ethics committee approved the study (No. INT 21/16, 28 January 2016).
Results
The population consisted of 24 males, 16 females, median age 68, range (14–84) years; 8/20 adenocarcinoma patients received chemotherapy. In all the Langerhans insulae (40/40) pancreatic alpha cells were found to express FAP, with a score of 2. No difference was found among NET(20/20) and adenocarcinoma(20/20); nor according to neoadjuvant chemotherapy in the adenocarcinoma cohort (received or not received).
Conclusion
Pancreatic Langerhans islets alpha cells normally express FAP. This is not expected to influence the diagnostic accuracy of FAP-targeting tracers. In the therapeutic setting, our results suggest the need to better elucidate FAPI radioligands’ effects on the Langerhans insulae function.
Surgical management of spinal arachnoid web in case of syringomyelia: Strategies and outcomes
Authors: Adib Sasan Darius , Schittenhelm Jens , Kurucz Peter , Hauser Till-Karsten , Tatagiba Marcos
Published: March 2023

Spinal arachnoid web (SAW) is a rare disease entity characterized as band-like arachnoid tissue that can cause spinal cord compression and syringomyelia. This study aimed to analyze the surgical management of spinal arachnoid web in patients with syringomyelia, focusing on surgical strategies and outcomes.
A total of 135 patients with syringomyelia underwent surgery at our department between November 2003 and December 2022. All patients underwent magnetic resonance imaging (MRI), with a special syringomyelia protocol (including TrueFISP and cine), and electrophysiology. Among these patients, we searched for patients with SAW with syringomyelia following careful analysis of neuroradiological data and surgical reports. The criteria for SAW were as follows: displacement of the spinal cord, disturbed but preserved CSF flow, and intraoperative arachnoid web. Patients were evaluated for initial symptoms, surgical strategies, and complications by reviewing surgical reports, patient documents, neuroradiological data, and follow-up data.
Of the 135 patients, 3 (2.22%) fulfilled the SAW criteria. The mean patient age was 51.67 ± 8.33 years. Two patients were male, and one was female. The affected levels were TH2/3, TH6, and TH8. Excision of arachnoid web was performed in all cases. No significant change in intraoperative monitoring was noted. Postoperatively, none of the patients presented new neurological symptoms. The MRI 3 months after surgery revealed that the syringomyelia improved in all cases, and caliber variation of the spinal cord could not be detected anymore. All clinical symptoms improved.
In summary SAW can be safely treated by surgery. Even syringomyelia usually improves inMRI and symptoms also improves, residual symptoms might be observed.
Ballistic performance of an FRP helmet-head system
Authors: Liu Y. J. , Xin S. H. , Wen H. M.
Published: March 2023

The purpose of this paper is to make an assessment on the performance of an FRP helmet-head system subjected to ballistic impact. Firstly, an FE model for human head is developed in which it mainly consists of scalp, skull, meanings, cerebrospinal fluid, brain tissue, falx, tentorium, face and neck. Constitutive models for each component of the head are determined and, in particular, strain rate effects of the compact bone of skull and the hyperelastic property of scalp are taken into account for the first time. Secondly, an FE model for Kevlar fibre reinforced phenolic helmet are constructed based on PASGT helmet. Recently developed dynamic constitutive models for metals and FRP laminates are employed for FMJ bullet and the KFRP helmet, respectively in the present study. Finally, both the head and helmet models are validated against available test data. Furthermore, effects of padding system (strap-netting and OA foam), impact position (top, front, lateral and rear), and projectile type (FSP and FMJ) on the ballistic performance of the helmet-head system have been systematically investigated with special attention being paid to the severity of head injury. It is found that the performance of the helmet with OA foam is advantageous over that of the helmet with strap-netting in head injury prevention; that the most harmful impact positions are different for helmets with different liner systems. It is also found that a lower velocity (358m/s) FMJ bullet pose more threats to head injury than a higher velocity (610m/s) FSP for the PASGT helmet-head system.