bluuebunny/crossref_metadata_2025_split huggingface dataset:
The economic cost of bovine trypanosomosis in pastoral and ago pastoral communities surrounding Murchision Falls National park, Buliisa district, Uganda
Authors: Kizza Daniel , Ocaido Michael , Mugisha Anthony , Azuba Rose , Nalubwama Sylvia , Nalule Sarah , Onyuth Howard , Musinguzi Simon Peter , Waiswa Charles 
Published: October 2022

AbstractBackground:Animal diseases that are endemic like tsetse transmitted trypanosomosis cause the continuous expenditure of financial resources of livestock farmers and loss of productivity of livestock. Estimating the cost of controlling animal trypanosomosis can provide evidence for priority setting and targeting cost-effective control strategies.Methodology:A cross-sectional survey to estimate the economic cost of bovine trypanosomosis was conducted in cattle-keeping communities living around Murchision falls National Park, in Buliisa district Uganda. Data was collected on herd structure, the cost of treatment and control, prevalence of morbidity and mortality rates due to trypanosomosis, and salvage sales losses in cattle herds in the last year.Results:In this study, 55.4% (n = 87) of the households reported their cattle had been affected by trypanosomosis during the previous last year. There was a high economic cost of trypanosomosis (USD 653) per household in cattle-keeping communities in Buliisa district of which 83% and 9% were due to mortality and milk loss respectively/ High mortality loss was due to low investment in treatment. The study showed that prophylactic treatment 3 times a year of the whole herd of cattle using Samorin ® (Isometamidium chloride) at a cost of USD 110 could drastically reduce cattle mortality loss due to trypanosomosis due to trypanosomosis with a return on investment of USD 540 annually per herd. This could be coupled with strategic restricted insecticide spraying of cattle with deltamethrin products.Conclusion:The results show a high economic cost of trypanosomosis in cattle-keeping communities in Buliisa district, with cattle mortality contributing the largest proportion of the economic cost. The high mortality loss was due to low investment in treatment of sick cattle.
Tumor microenvironment: barrier or opportunity towards effective cancer therapy
Authors: Tiwari Aadhya , Trivedi Rakesh , Lin Shiaw-Yih 
Published: October 2022

AbstractTumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME’s individual components and their interplay at higher resolution. Deeper understanding of the immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a possibility of reprogramming of TME components to overcome the widely prevailing issue of immunotherapeutic resistance. The focus of the present review is to understand the complexity of TME and comprehending future perspective of its components as potential therapeutic targets. The later part of the review describes the sophisticated 3D models emerging as valuable means to study TME components and an extensive account of advanced bioinformatic tools to profile TME components and predict neoantigens. Overall, this review provides a comprehensive account of the current knowledge available to target TME.
Quarantining: a mentally distressful but physically comfortable experience in South Korea
Authors: Kwon Hye-Young , Kim Yongjoo , Lee Seung-Young , Kim Chang-Bo 
Published: October 2022

Abstract
Objective
Quarantine is the first response to the COVID-19 pandemic. Restricting daily life can cause several problems. This study aimed to measure the impact of the COVID-19 quarantine on health-related quality of life (HRQoL) by comparing to the pre-pandemic.

Methods
HRQoL during COVID-19 quarantine was surveyed online using EQ-5D index and matched to that of the pre-pandemic-extracted from nationwide representative data of the Korea Community Health Survey- with propensity scores. A beta regression for the EQ-5D scores and a logistic analysis for individual dimensions of the EQ-5D index were performed to measure the impact of the COVID-19 quarantine on health utility.

Results
The overall scores of the EQ-5D index were significantly higher in the group under quarantine during the COVID-19 pandemic (0.971 SD 0.064) than those before the pandemic (0.964 SD 0.079, Diff. 0.007 SD 0.101, p = 0.043). The beta regression for the overall scores of EQ-5D revealed that quarantining during the COVID-19 pandemic increased by 52.7% compared to normal life before the outbreak(p = 0.045). Specifically, “Depression/Anxiety” deteriorated significantly during quarantining (OR = 0.62, 95% CI:0.48–0.80). However, “Pain/Discomfort” and “Mobility” significantly improved (OR = 5.37, 95% CI:3.71–7.78 and OR = 2.05, 95% CI:1.11–3.80, respectively).

Conclusion
Although the world is facing a challenging moment that it has never been through before, mandatory quarantine has served as an experience that provided mental distress but physical comfort in the Korean context.
Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer
Authors: Wu Xiang , Zhou Shuping , Zhou Xinhua , Xu Xiao , Wang Luoluo , Ruan Yi , Lu Jun , Li Haili , Xu Hongfeng , Ma Xinyi , Li Hong 
Published: October 2022

Abstract
Background
Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer.

Case presentation
AC1
A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported.

Discussion
For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.
Surgical explantation of quaternate transcatheter aortic valve replacement bioprostheses: a case report
Authors: Liang Mengya , Jian Bohao , Chen Guangxian , Wu Zhongkai 
Published: October 2022

Abstract
Background
Transcatheter aortic valve replacement (TAVR) is a growing less invasive surrogate for high-risk patients with aortic valve disease. Although the number of TAVR procedures is growing rapidly, TAVR prosthesis surgical explantation are rare procedures but increasing in frequency.

Case presentation
We herein presented a case of 68-year-old male who underwent quaternate TAVR bioprostheses implantation. Three months later, his symptoms deteriorated due to aggravated paravalvular leakage and severe mitral regurgitation. A challenging surgical explantation procedure was therefore performed. During the surgery, lethal penetrations of aortic wall due to migration of these devices were found and four bioprostheses were integrally explanted. The native calcified aortic leaflet was removed and replaced with a 23 mm. The impaired segment of ascending aorta was replaced with a Dacron graft afterwards.

Conclusions
In summary, we presented a surgical case of explantation of four TAVR Bioprostheses, which is so far the maximum number of surgical-explant devices ever reported. This extreme individual case aggregates our technical experiences with this unique category of patients and raise the concern of the best initial valve strategy for relatively younger patients with severe aortic valve stenosis.
Monitoring antimicrobial usage in companion animals: exploring the use of the Danish VetStat database
Authors: Glavind Anne-Sofie , Kruse Amanda Brinch , Nielsen Liza Rosenbaum , Stege Helle 
Published: October 2022

Abstract
Background
In the Danish Veterinary Statistics Program, VetStat, sales data on medicinal products prescribed for veterinary consumption is collected. The Danish Food and Veterinary Administration (DVFA) manages the database and each purchase contains detailed product-specific information linked with a species-specific ID. National surveillance systems are also implemented or being developed in the other European Union Member States. By 2029, all Member States are required to report data on antimicrobial usage for companion animals to the European Medicines Agency. This study aimed to assess the challenges encountered when using the VetStat database to quantify antimicrobial use in Danish companion animals. Raw VetStat data were propagated by the DVFA and originated from veterinary practitioners and Danish pharmacies.

Results
Comprehensive estimates of antimicrobial use in Danish companion animals were not readily available due to database construct. Antimicrobials sold for use in companion animals (linked to a companion animal ID) comprised a large number of products licensed solely for horses or livestock, while data assigned a replacement code encompassed both topical and peroral antimicrobials licensed for companion animals. Additionally, antimicrobials sold from pharmacies to veterinary practitioners presented the biggest challenge in data retrieval and validation. Treatment data are only transferred to VetStat through the billing systems when Danish veterinarians are treating livestock, but not companion animals. Information on products sold for in-house use in companion animals is only available from pharmacy records without a species-specific ID. As a result, parenteral antimicrobials with multi-species authorization utilized by small animal veterinary practitioners are not accounted for in the overall estimate for companion animals.

Conclusions
Owing to the database structure and requirements for data entry, antimicrobial use in companion animals is an approximation. The actual consumption may be significantly higher than what is currently calculated from the database, as the majority of parenteral products are not included. Consumption data can be measured more accurately provided treatment data from veterinary practitioners in small or mixed practices are transferred to the database through the billing system. This would equal the legal requirements for Danish veterinary practitioners treating livestock.
Synthesis and characterization of growth factor free nanoengineered bioactive scaffolds for bone tissue engineering
Authors: Abedi Fatemeh , Moghaddam Sevil Vaghefi , Ghandforoushan Parisa , Aghazadeh Marziyeh , Ebadi Hafez , Davaran Soodabeh 
Published: October 2022

Abstract
Background
To address the obstacles that come with orthopedic surgery for biological graft tissues, including immune rejections, bacterial infections, and weak osseointegration, bioactive nanocomposites have been used as an alternative for bone grafting since they can mimic the biological and mechanical properties of the native bone. Among them, PCL-PEG-PCL (PCEC) copolymer has gained much attention for bone tissue engineering as a result of its biocompatibility and ability for osteogenesis.

Methods
Here, we designed a growth factor-free nanoengineered scaffold based on the incorporation of Fe3O4 and hydroxyapatite (HA) nanoparticles into the PCL-PEG-PCL/Gelatin (PCEC/Gel) nanocomposite. We characterized different formulations of nanocomposite scaffolds in terms of physicochemical properties. Also, the mechanical property and specific surface area of the prepared scaffolds, as well as their feasibility for human dental pulp stem cells (hDPSCs) adhesion were assessed.

Results
The results of in vitro cell culture study revealed that the PCEC/Gel Fe3O4&HA scaffold could promote osteogenesis in comparison with the bare scaffold, which confirmed the positive effect of the Fe3O4 and HA nanoparticles in the osteogenic differentiation of hDPSCs.

Conclusion
The incorporation of Fe3O4 and HA with PCEC/gelatin could enhance osteogenic differentiation of hDPSCs for possible substitution of bone grafting tissue.

Graphical Abstract
The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment
Authors: Li Shuangying , Wang Liangliang , Wang Yuanyuan , Zhang Changyi , Hong Zhenya , Han Zhiqiang 
Published: October 2022

AbstractContinuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division. Based on their distinct functions in cell cycle control, cell cycle checkpoints are classified into two groups: DNA damage checkpoints and DNA replication stress checkpoints. The DNA damage checkpoints (ATM-CHK2-p53) primarily monitor genetic errors and arrest cell cycle progression to facilitate DNA repair. Unfortunately, genes involved in DNA damage checkpoints are frequently mutated in human malignancies. In contrast, genes associated with DNA replication stress checkpoints (ATR-CHK1-WEE1) are rarely mutated in tumors, and cancer cells are highly dependent on these genes to prevent replication catastrophe and secure genome integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through “synthetic lethality” mechanism with mutant DNA repair pathways genes in cancer cells. However, an increasing number of patients are acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that a combination therapy of targeting cell cycle checkpoints and PARPs act synergistically to increase the number of DNA errors, compromise the DNA repair machinery, and disrupt the cell cycle, thereby increasing the death rate of cancer cells with DNA repair deficiency or PARP inhibitor resistance. We highlight a combinational strategy involving PARP inhibitors and inhibition of two major cell cycle checkpoint pathways, ATM-CHK2-TP53 and ATR-CHK1-WEE1. The biological functions, resistance mechanisms against PARP inhibitors, advances in preclinical research, and clinical trials are also reviewed.
Normalization and de-noising of single-cell Hi-C data with BandNorm and scVI-3D
Authors: Zheng Ye , Shen Siqi , Keleş Sündüz 
Published: October 2022

AbstractSingle-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, and a deep generative modeling framework, scVI-3D, to account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in a time and memory efficient manner for cell-type separation, identification of interacting loci, and recovery of cell-type relationships, while scVI-3D exhibits advantages for rare cell types and under high sparsity scenarios. Application of BandNorm coupled with gene-associating domain analysis reveals scRNA-seq validated sub-cell type identification.
Evaluation of cell-cell interaction methods by integrating single-cell RNA sequencing data with spatial information
Authors: Liu Zhaoyang , Sun Dongqing , Wang Chenfei 
Published: October 2022

Abstract
Background
Cell-cell interactions are important for information exchange between different cells, which are the fundamental basis of many biological processes. Recent advances in single-cell RNA sequencing (scRNA-seq) enable the characterization of cell-cell interactions using computational methods. However, it is hard to evaluate these methods since no ground truth is provided. Spatial transcriptomics (ST) data profiles the relative position of different cells. We propose that the spatial distance suggests the interaction tendency of different cell types, thus could be used for evaluating cell-cell interaction tools.

Results
We benchmark 16 cell-cell interaction methods by integrating scRNA-seq with ST data. We characterize cell-cell interactions into short-range and long-range interactions using spatial distance distributions between ligands and receptors. Based on this classification, we define the distance enrichment score and apply an evaluation workflow to 16 cell-cell interaction tools using 15 simulated and 5 real scRNA-seq and ST datasets. We also compare the consistency of the results from single tools with the commonly identified interactions. Our results suggest that the interactions predicted by different tools are highly dynamic, and the statistical-based methods show overall better performance than network-based methods and ST-based methods.

Conclusions
Our study presents a comprehensive evaluation of cell-cell interaction tools for scRNA-seq. CellChat, CellPhoneDB, NicheNet, and ICELLNET show overall better performance than other tools in terms of consistency with spatial tendency and software scalability. We recommend using results from at least two methods to ensure the accuracy of identified interactions. We have packaged the benchmark workflow with detailed documentation at GitHub (https://github.com/wanglabtongji/CCI).
Evolutionary dynamics of pseudoautosomal region 1 in humans and great apes
Authors: Bergman Juraj , Schierup Mikkel Heide 
Published: October 2022

Abstract
Background
The pseudoautosomal region 1 (PAR1) is a 2.7 Mb telomeric region of human sex chromosomes. PAR1 has a crucial role in ensuring proper segregation of sex chromosomes during male meiosis, exposing it to extreme recombination and mutation processes. We investigate PAR1 evolution using population genomic datasets of extant humans, eight populations of great apes, and two archaic human genome sequences.

Results
We find that PAR1 is fast evolving and closer to evolutionary nucleotide equilibrium than autosomal telomeres. We detect a difference between substitution patterns and extant diversity in PAR1, mainly driven by the conflict between strong mutation and recombination-associated fixation bias at CpG sites. We detect excess C-to-G mutations in PAR1 of all great apes, specific to the mutagenic effect of male recombination. Despite recent evidence for Y chromosome introgression from humans into Neanderthals, we find that the Neanderthal PAR1 retained similarity to the Denisovan sequence. We find differences between substitution spectra of these archaics suggesting rapid evolution of PAR1 in recent hominin history. Frequency analysis of alleles segregating in females and males provided no evidence for recent sexual antagonism in this region. We study repeat content and double-strand break hotspot regions in PAR1 and find that they may play roles in ensuring the obligate X-Y recombination event during male meiosis.

Conclusions
Our study provides an unprecedented quantification of population genetic forces governing PAR1 biology across extant and extinct hominids. PAR1 evolutionary dynamics are predominantly governed by recombination processes with a strong impact on mutation patterns across all species.
Local CpG density affects the trajectory and variance of age-associated DNA methylation changes
Authors: Higham Jonathan , Kerr Lyndsay , Zhang Qian , Walker Rosie M. , Harris Sarah E. , Howard David M. , Hawkins Emma L. , Sandu Anca-Larisa , Steele J. Douglas , Waiter Gordon D. , Murray Alison D. , Evans Kathryn L. , McIntosh Andrew M. , Visscher Peter M. , Deary Ian J. , Cox Simon R. , Sproul Duncan 
Published: October 2022

AbstractBackgroundDNA methylation is an epigenetic mark associated with the repression of gene promoters. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Altered rates of aging inferred from these clocks are observed in human disease. However, the molecular mechanisms underpinning age-associated DNA methylation changes remain unknown. Local DNA sequence can program steady-state DNA methylation levels, but how it influences age-associated methylation changes is unknown.ResultsWe analyze longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs. We show that changes in methylation with age occur at 182,760 loci largely independently of variation in cell type proportions. These changes are especially apparent at 8322 low CpG density loci. Using SNP data from the same individuals, we demonstrate that methylation trajectories are affected by local sequence polymorphisms at 1487 low CpG density loci. More generally, we find that low CpG density regions are particularly prone to change and do so variably between individuals in people aged over 65. This differs from the behavior of these regions in younger individuals where they predominantly lose methylation.ConclusionsOur results, which we reproduce in two independent groups of individuals, demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.
Global early replication disrupts gene expression and chromatin conformation in a single cell cycle
Authors: Santos Miguel M. , Johnson Mark C. , Fiedler Lukáš , Zegerman Philip 
Published: October 2022

Abstract
Background
The early embryonic divisions of many organisms, including fish, flies, and frogs, are characterized by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear.

Results
Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of the majority of origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly implicating origin firing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape.

Conclusions
Together, these data provide new insight into the role of the temporal control of origin firing during S-phase for coordinating replication, gene expression, and chromatin establishment as occurs in the early embryo.