bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbon dots as a novel photosensitizer for photodynamic therapy of cancer and bacterial infectious diseases: recent advances
Authors: Sun Lingxiang , Zhao Yifan , Peng Hongyi , Zhou Jian , Zhang Qingmei , Yan Jingyu , Liu Yingyu , Guo Susu , Wu Xiuping , Li Bing 
Published: April 2024

AbstractCarbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.
Graphical Abstract
Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study
Authors: Kim Juwan , Hong Seung Soo , Kim Sung Hyun , Hwang Ho Kyong , Kang Chang Moo 
Published: April 2024

Abstract
Background
Pancreatic neuroendocrine tumors (PNETs) represent 1–2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched.

Methods
This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test.

Results
Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence.

Conclusion
This study’s findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious “wait-and-see” approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.
Targeting Wnt/β-catenin signaling and its interplay with TGF-β and Notch signaling pathways for the treatment of chronic wounds
Authors: Gumede Dimakatso B. , Abrahamse Heidi , Houreld Nicolette N. 
Published: April 2024

AbstractWound healing is a tightly regulated process that ensures tissue repair and normal function following injury. It is modulated by activation of pathways such as the transforming growth factor-beta (TGF-β), Notch, and Wnt/β-catenin signaling pathways. Dysregulation of this process causes poor wound healing, which leads to tissue fibrosis and ulcerative wounds. The Wnt/β-catenin pathway is involved in all phases of wound healing, primarily in the proliferative phase for formation of granulation tissue. This review focuses on the role of the Wnt/β-catenin signaling pathway in wound healing, and its transcriptional regulation of target genes. The crosstalk between Wnt/β-catenin, Notch, and the TGF-β signaling pathways, as well as the deregulation of Wnt/β-catenin signaling in chronic wounds are also considered, with a special focus on diabetic ulcers. Lastly, we discuss current and prospective therapies for chronic wounds, with a primary focus on strategies that target the Wnt/β-catenin signaling pathway such as photobiomodulation for healing diabetic ulcers.
Using functional principal component analysis (FPCA) to quantify sitting patterns derived from wearable sensors
Authors: Zablocki Rong W. , Hartman Sheri J. , Di Chongzhi , Zou Jingjing , Carlson Jordan A. , Hibbing Paul R. , Rosenberg Dori E. , Greenwood-Hickman Mikael Anne , Dillon Lindsay , LaCroix Andrea Z. , Natarajan Loki 
Published: April 2024

Abstract
Background
Sedentary behavior (SB) is a recognized risk factor for many chronic diseases. ActiGraph and activPAL are two commonly used wearable accelerometers in SB research. The former measures body movement and the latter measures body posture. The goal of the current study is to quantify the pattern and variation of movement (by ActiGraph activity counts) during activPAL-identified sitting events, and examine associations between patterns and health-related outcomes, such as systolic and diastolic blood pressure (SBP and DBP).

Methods
The current study included 314 overweight postmenopausal women, who were instructed to wear an activPAL (at thigh) and ActiGraph (at waist) simultaneously for 24 hours a day for a week under free-living conditions. ActiGraph and activPAL data were processed to obtain minute-level time-series outputs. Multilevel functional principal component analysis (MFPCA) was applied to minute-level ActiGraph activity counts within activPAL-identified sitting bouts to investigate variation in movement while sitting across subjects and days. The multilevel approach accounted for the nesting of days within subjects.

Results
At least 90% of the overall variation of activity counts was explained by two subject-level principal components (PC) and six day-level PCs, hence dramatically reducing the dimensions from the original minute-level scale. The first subject-level PC captured patterns of fluctuation in movement during sitting, whereas the second subject-level PC delineated variation in movement during different lengths of sitting bouts: shorter (< 30 minutes), medium (30 -39 minutes) or longer (> 39 minute). The first subject-level PC scores showed positive association with DBP (standardized $$\hat{\beta }$$

β
^

: 2.041, standard error: 0.607, adjusted p = 0.007), which implied that lower activity counts (during sitting) were associated with higher DBP.

Conclusion
In this work we implemented MFPCA to identify variation in movement patterns during sitting bouts, and showed that these patterns were associated with cardiovascular health. Unlike existing methods, MFPCA does not require pre-specified cut-points to define activity intensity, and thus offers a novel powerful statistical tool to elucidate variation in SB patterns and health.

Trial registration
ClinicalTrials.gov NCT03473145; Registered 22 March 2018; https://clinicaltrials.gov/ct2/show/NCT03473145; International Registered Report Identifier (IRRID): DERR1-10.2196/28684
Vpr driving DNA methylation variation of CD4 + T cells in HIV-1 infection
Authors: Wang Peipei , Meng Zhuoyue , Deng Kai , Gao Zhiliang , Cai Jinfeng 
Published: April 2024

Abstract
Background
Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted.

Methods
In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection.

Results
We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes.

Conclusions
These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.
Quality of occlusal outcome in adult class II patients after maxillary total arch distalization with interradicular mini-screws
Authors: Janssens Yann , Foley Patrick F. , Beyling Frauke , Schwestka-Polly Rainer , Schmid Jonas Q. 
Published: April 2024

Abstract
Background
The aim of the investigation was to evaluate if a Class II malocclusion in adult patients can be successfully corrected by maxillary total arch distalization with interradicular mini-screws in combination with completely customized lingual appliances (CCLA).

Methods
Two patient groups were matched for age and gender to determine differences in the quality of final treatment outcome. The treatment results of 40 adult patients with a Class I malocclusion (Group 1) were compared with those of 40 adult patients with a moderate to severe Class II malocclusion (Group 2). All patients had completed treatment with a CCLA (WIN, DW Lingual Systems, Bad Essen, Germany) without overcorrection in the individual treatment plan defined by a target set-up. To compare the treatment results of the two groups, 7 measurements using the American Board of Orthodontics Model Grading System (ABO MGS) and linear measurements for anterior-posterior (AP) and vertical dimensions were assessed at the start of lingual treatment (T1), after debonding (T2B), and compared to the individual target set-up (T2A).

Results
A statistically significant AP correction (mean 4.5 mm, min/max 2.1/8.6, SD 1.09) was achieved in Group 2, representing 99% of the planned amount. The planned overbite correction was fully achieved in both the Class I and Class II groups. There was a statistically significant improvement in the ABO scores in both groups (Group 1: 39.4 to 17.7, Group 2: 55.8 to 17.1), with no significant difference between the two groups at T2B. 95% of the adult patients in Group 1 and 95% in Group 2 would meet the ABO standards after maxillary total arch distalization with a CCLA and interradicular mini-screws.

Conclusions
CCLAs in combination with interradicular mini-screws for maxillary total arch distalization can successfully correct moderate to severe Class II malocclusions in adult patients. The quality of the final occlusal outcome is high and the amount of the sagittal correction can be predicted by the individual target set-up.
Researchers should no longer delay implementation of Pap screening in low and middle income countries pending research into novel screening approaches
Authors: Suba Eric J 
Published: April 2024

AbstractA study coordinated by Groesbeck Parham and Mark Schiffman describes a novel approach to single-visit, point-of-care cervical screening and triage for low and middle income countries (LMICs) that uses an HPV screening test that is not affordable in LMICs combined with a triage test that is not available at the point of care. Pap smears are feasible, affordable, and well-suited for single-visit, point-of-care cervical screening and triage in LMICs. Research into a discredited cervical screening test, funded by the US National Cancer Institute, contributed to at least 500,000 preventable cervical cancer deaths by delaying implementation of Pap screening throughout India for 18 years. Researchers should no longer delay implementation of Pap screening in LMICs pending research into novel screening approaches. Instead, researchers should prioritize cervical screening approaches that will save as many lives as quickly as possible in LMICs. To that end, Parham et al. should implement good-quality, single-visit, point-of-care Pap smear screening in LMICs until better-quality, single-visit, point-of-care HPV screening becomes widely affordable in LMICs.
hadge: a comprehensive pipeline for donor deconvolution in single-cell studies
Authors: Curion Fabiola , Wu Xichen , Heumos Lukas , André Mylene Mariana Gonzales , Halle Lennard , Ozols Matiss , Grant-Peters Melissa , Rich-Griffin Charlotte , Yeung Hing-Yuen , Dendrou Calliope A. , Schiller Herbert B. , Theis Fabian J. 
Published: April 2024

AbstractSingle-cell multiplexing techniques (cell hashing and genetic multiplexing) combine multiple samples, optimizing sample processing and reducing costs. Cell hashing conjugates antibody-tags or chemical-oligonucleotides to cell membranes, while genetic multiplexing allows to mix genetically diverse samples and relies on aggregation of RNA reads at known genomic coordinates. We develop hadge (hashing deconvolution combined with genotype information), a Nextflow pipeline that combines 12 methods to perform both hashing- and genotype-based deconvolution. We propose a joint deconvolution strategy combining best-performing methods and demonstrate how this approach leads to the recovery of previously discarded cells in a nuclei hashing of fresh-frozen brain tissue.
Clustering of predicted loss-of-function variants in genes linked with monogenic disease can explain incomplete penetrance
Authors: Beaumont Robin N. , Hawkes Gareth , Gunning Adam C. , Wright Caroline F. 
Published: April 2024

Abstract
Background
Genetic variants that severely alter protein products (e.g. nonsense, frameshift) are often associated with disease. For some genes, these predicted loss-of-function variants (pLoFs) are observed throughout the gene, whilst in others, they occur only at specific locations. We hypothesised that, for genes linked with monogenic diseases that display incomplete penetrance, pLoF variants present in apparently unaffected individuals may be limited to regions where pLoFs are tolerated. To test this, we investigated whether pLoF location could explain instances of incomplete penetrance of variants expected to be pathogenic for Mendelian conditions.

Methods
We used exome sequence data in 454,773 individuals in the UK Biobank (UKB) to investigate the locations of pLoFs in a population cohort. We counted numbers of unique pLoF, missense, and synonymous variants in UKB in each quintile of the coding sequence (CDS) of all protein-coding genes and clustered the variants using Gaussian mixture models. We limited the analyses to genes with ≥ 5 variants of each type (16,473 genes). We compared the locations of pLoFs in UKB with all theoretically possible pLoFs in a transcript, and pathogenic pLoFs from ClinVar, and performed simulations to estimate the false-positive rate of non-uniformly distributed variants.

Results
For most genes, all variant classes fell into clusters representing broadly uniform variant distributions, but genes in which haploinsufficiency causes developmental disorders were less likely to have uniform pLoF distribution than other genes (P < 2.2 × 10−6). We identified a number of genes, including ARID1B and GATA6, where pLoF variants in the first quarter of the CDS were rescued by the presence of an alternative translation start site and should not be reported as pathogenic. For other genes, such as ODC1, pLoFs were located approximately uniformly across the gene, but pathogenic pLoFs were clustered only at the end, consistent with a gain-of-function disease mechanism.

Conclusions
Our results suggest the potential benefits of localised constraint metrics and that the location of pLoF variants should be considered when interpreting variants.
An unusual case of severe asphyxia with the fetal position unexpectedly inverted in a malformed uterus: a case report
Authors: Abe Jiro , Nasu Takashi , Noro Ayumu , Tsubaki Junko 
Published: April 2024

Abstract
Background
We present a severe neonatal consequence due to the unexpected and crucial inversion of the fetal position after sudden termination of tocolysis during early labor of a woman with congenital uterine anomaly. It has been reported that congenital uterine anomalies latently affect the fetal position. The clinical pitfalls in childbirth with uterine anomalies are discussed here on the basis of clinical evidence.

Case presentation
At a perinatal medical center in Japan, a 29-year-old Japanese mother who had a history of bicornuate uterus, received tocolysis to prolong her pregnancy for 5 days during the late preterm period after preterm-premature rupture of the membrane. She gave birth to a 2304 g male neonate of the gestational age of 35 weeks and 5 days with severe asphyxia by means of crash cesarean section for fetal sustained bradycardia after sudden termination of tocolysis. We found the fetal position to reverse from cephalic to breech position during early labor. He ended up having severe cerebral palsy after brain cooling against hypoxic-ischemic encephalopathy for 3 days. The mechanism of inversion from cephalic to breech position without amnionic fluid remains unclear, although women with a known diagnosis of a uterine anomaly have higher risk of adverse outcomes such as malpresentation.

Conclusions
When considering the clinical course of this case on the basis of the medical reports, we suspected that uterine anomalies and changes in intrauterine pressure could cause fetal malpresentation and adverse neonatal outcomes.
Biodistribution and radiation dosimetry of [99mTc]Tc-N4-BTG in patients with biochemical recurrence of prostate cancer
Authors: Rinscheid Andreas , Gäble Alexander , Wienand Georgine , Dierks Alexander , Kircher Malte , Günther Thomas , Patt Marianne , Bundschuh Ralph A. , Lapa Constantin , Pfob Christian H. 
Published: April 2024

Abstract
Background
In patients with prostate cancer (PCa), imaging with gastrin-releasing peptide receptor (GRPR) ligands is an alternative to PSMA-targeted tracers, particularly if PSMA expression is low or absent. [99mTc]Tc-N4-BTG is a newly developed GRPR-directed probe for conventional scintigraphy and single photon emission computed tomography (SPECT) imaging. The current study aims to investigate the safety, biodistribution and dosimetry of [99mTc]Tc-N4-BTG in patients with biochemical recurrence (BCR) of PCa.

Results
No adverse pharmacologic effects were observed. Injection of [99mTc]Tc-N4-BTG resulted in an effective dose of 0.0027 ± 0.0002 mSv/MBq. The urinary bladder was the critical organ with the highest mean absorbed dose of 0.028 ± 0.001 mGy/MBq, followed by the pancreas with 0.0043 ± 0.0015 mGy/MBq, osteogenic cells with 0.0039 ± 0.0005 mGy/MBq, the kidneys with 0.0034 ± 0.0003 mGy/MBq, and the liver with 0.0019 ± 0.0004 mGy/MBq, respectively. No focal tracer uptake suggestive of PCa recurrence could be revealed for any of the patients.

Conclusion
[99mTc]Tc-N4-BTG appears to be a safe diagnostic agent. Compared to GRPR-targeted PET tracers, this 99mTc-labelled SPECT agent could contribute to a broader application and better availability of this novel approach. Further research to assess its clinical value is warranted.
Interactions between avian viruses and skin in farm birds
Authors: Souci Laurent , Denesvre Caroline 
Published: April 2024

AbstractThis article reviews the avian viruses that infect the skin of domestic farm birds of primary economic importance: chicken, duck, turkey, and goose. Many avian viruses (e.g., poxviruses, herpesviruses, Influenza viruses, retroviruses) leading to pathologies infect the skin and the appendages of these birds. Some of these viruses (e.g., Marek’s disease virus, avian influenza viruses) have had and/or still have a devasting impact on the poultry economy. The skin tropism of these viruses is key to the pathology and virus life cycle, in particular for virus entry, shedding, and/or transmission. In addition, for some emergent arboviruses, such as flaviviruses, the skin is often the entry gate of the virus after mosquito bites, whether or not the host develops symptoms (e.g., West Nile virus). Various avian skin models, from primary cells to three-dimensional models, are currently available to better understand virus-skin interactions (such as replication, pathogenesis, cell response, and co-infection). These models may be key to finding solutions to prevent or halt viral infection in poultry.