bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of PET tracing and biodistribution between 64Cu-labeled micro-and nano-polystyrene in a murine inhalation model
Authors: Shanmugiah Joycie , Zaheer Javeria , Im Changkeun , Kang Choong Mo , Kim Jin Su 
Published: January 2024

Abstract
Introduction
Recent studies showed the presence of microplastic in human lungs. There remains an unmet need to identify the biodistribution of microplastic after inhalation. In this study, we traced the biodistribution of inhaled micro-sized polystyrene (mPS) and/or nano-sized PS (nPS) using 64Cu with PET in mice.

Methods
We used 0.2–0.3-µm sized mPS and 20-nm sized nPS throughout. 64Cu-DOTA-mPS, 64Cu-DOTA-nPS and/or 64CuCl2 were used to trace the distribution in the murine inhalation model. PET images were acquired using an INVEON PET scanner at 1, 12, 24, 48, and 72 h after intratracheal instillation, and the SUVmax for interesting organs were determined, biodistribution was then determined in terms of percentage injected dose/gram of tissue (%ID/g). Ex vivo tissue-radio thin-layer chromatography (Ex vivo-radioTLC) was used to demonstrate the existence of 64Cu-DOTA-PS in tissue.

Results
PET image demonstrated that the amount of 64Cu-DOTA-mPS retained within the lung was significantly higher than 64Cu-DOTA-nPS until 72 h; SUVmax values of 64Cu-DOTA-mPS in lungs was 11.7 ± 5.0, 48.3 ± 6.2, 65.5 ± 2.3, 42.2 ± 13.1, and 13.2 ± 2.3 at 1, 12, 24, 48, and 72 h respectively whereas it was 31.2 ± 3.1, 17.3 ± 5.9, 10.0 ± 3.4, 8.1 ± 2.4 and 8.9 ± 3.6 for 64Cu-DOTA-nPS at the corresponding timepoints. The biodistribution data supported the PET data with a similar pattern of clearance of the radioactivity from the lung. nPS cleared rapidly post instillation in comparison to mPS within the lungs. Higher accumulation of %ID/g for nPS (roughly 2 times) were observed compared to mPS in spleen, liver, intestine, thymus, kidney, brain, salivary gland, ovary, and urinary bladder. Ex vivo-radioTLC was used to demonstrate that the detected gamma rays originated from 64Cu-DOTA-mPS or nPS.

Conclusion
PET image demonstrated the differences in accumulations of mPS and/or nPS between lungs and other interesting organs. The information provided may be used as the basis for future studies on the toxicity of mPS and/or nPS.

Graphical abstract
Relationship between paravertebral muscle function, pelvic incidence, and health-related quality of life in patients with degenerative spinal deformity
Authors: Chen Can , Tang Yong , Yang Sen , Dai Wei , Tan Jiulin , Yu Xueke , Zhang Chengmin , Luo Fei 
Published: January 2024

Abstract
Background
Patients with degenerative spinal deformity often experience symptoms that seriously affect their quality of life, such as low back pain and dysfunction. This study aimed to investigate the relationship between paravertebral muscle function and pelvic incidence (PI) and their effect on health-related quality of life (HRQL) in patients with degenerative spinal deformity.

Methods
A total of 112 patients with degenerative spinal deformity in Southwest Hospital (Chongqing, China) were enrolled. They were divided into groups according to PI angle: high (PI > 60°, n = 37), normal (PI 50°–60°, n = 31), and low (PI < 50°, n = 44). Paravertebral muscle strength and endurance were assessed using the prone external fixation test frame. The sagittal vertical axis (SVA) was measured on X-rays of the spine in an anterolateral position, and all subjects were assessed with the Oswestry Disability Index (ODI), Roland–Morris questionnaire (RMQ), and 36-Item Short Form Health Survey (SF-36). Pearson or Spearman coefficients were used to assess the relationship of paravertebral muscle function with SVA, PI, and health-related quality of life.

Results
Maximal voluntary exercise (MVE) in the high-PI group was significantly lower than the MVE of both the normal- and low-PI groups (p < 0.05). There was no significant difference in MVE between the normal- and low-PI groups (p > 0.05). There was no significant difference in endurance time, SVA, ODI, RMQ, and SF-36 among the three groups. Paravertebral muscle MVE was negatively correlated with PI, SVA, ODI, and RMQ (r = − 0.193, − 0.210, − 0.283, − 0.277, p < 0.05). Endurance time of paravertebral muscle was also negatively correlated with SVA, ODI, and RMQ (r =  − 0.200, − 0.420, − 0.348, p < 0.05) and positively correlated with SF-36 (r = 0.245, p < 0.05). In addition, paravertebral muscle MVE was positively correlated with the physical functioning score of the SF-36 (r = 0.251, p < 0.05), and the endurance time of paravertebral muscle was positively correlated with the physical functioning, physical role, bodily pain, and social function scores of the SF-36 (r = 0.342, 0.230, 0.209, 0.256, p < 0.05).

Conclusions
High PI may serve as a risk factor for decreased paraspinal muscle strength in patients with degenerative spinal deformities. Early and targeted exercises focusing on paraspinal muscle strength and endurance could potentially be of positive significance in slowing down the progression of sagittal imbalance, alleviating functional disorders, and increasing health-related quality of life in patients with degenerative spinal deformity.
Rett syndrome in Ireland: a demographic study
Authors: Zade Komal , Campbell Ciara , Bach Snow , Fernandes Hazel , Tropea Daniela 
Published: January 2024

Abstract
Background
Rett syndrome (RTT) is a rare neurodevelopmental condition associated with mutations in the gene coding for the methyl-CpG-binding protein 2 (MECP2). It is primarily observed in girls and affects individuals globally. The understanding of the neurobiology of RTT and patient management has been improved by studies that describe the demographic and clinical presentation of individuals with RTT. However, in Ireland, there is a scarcity of data regarding individuals with RTT, which impedes the ability to fully characterize the Irish RTT population. Together with the Rett Syndrome Association of Ireland (RSAI), we prepared a questionnaire to determine the characteristics of RTT individuals in Ireland. Twenty-five families have participated in the study to date, providing information about demographics, genetics, familial history, clinical features, and regression.

Results
The results show that Irish individuals with RTT have comparable presentation with respect to individuals in other countries; however, they had a better response to anti-epileptic drugs, and fewer skeletal deformities were reported. Nonetheless, seizures, involuntary movements and regression were more frequently observed in Irish individuals. One of the main findings of this study is the limited genetic information available to individuals to support the clinical diagnosis of RTT.

Conclusions
Despite the limited sample size, this study is the first to characterize the RTT population in Ireland and highlights the importance of having a swift access to genetic testing to sharpen the characterization of the phenotype and increase the visibility of Irish individuals in the international RTT community.

Graphical abstract
TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer
Authors: Lynce Filipa , Stevens Laura E. , Li Zheqi , Brock Jane E. , Gulvady Anushree , Huang Ying , Nakhlis Faina , Patel Ashka , Force Jeremy M. , Haddad Tufia C. , Ueno Naoto , Stearns Vered , Wolff Antonio C. , Clark Amy S. , Bellon Jennifer R. , Richardson Edward T. , Balko Justin M. , Krop Ian E. , Winer Eric P. , Lange Paulina , Hwang E. Shelley , King Tari A. , Tolaney Sara M. , Thompson Alastair , Gupta Gaorav P. , Mittendorf Elizabeth A. , Regan Meredith M. , Overmoyer Beth , Polyak Kornelia 
Published: January 2024

Abstract
Background
Patients with inflammatory breast cancer (IBC) have overall poor clinical outcomes, with triple-negative IBC (TN-IBC) being associated with the worst survival, warranting the investigation of novel therapies. Preclinical studies implied that ruxolitinib (RUX), a JAK1/2 inhibitor, may be an effective therapy for TN-IBC.

Methods
We conducted a randomized phase II study with nested window-of-opportunity in TN-IBC. Treatment-naïve patients received a 7-day run-in of RUX alone or RUX plus paclitaxel (PAC). After the run-in, those who received RUX alone proceeded to neoadjuvant therapy with either RUX + PAC or PAC alone for 12 weeks; those who had received RUX + PAC continued treatment for 12 weeks. All patients subsequently received 4 cycles of doxorubicin plus cyclophosphamide prior to surgery. Research tumor biopsies were performed at baseline (pre-run-in) and after run-in therapy. Tumors were evaluated for phosphorylated STAT3 (pSTAT3) by immunostaining, and a subset was also analyzed by RNA-seq. The primary endpoint was the percent of pSTAT3-positive pre-run-in tumors that became pSTAT3-negative. Secondary endpoints included pathologic complete response (pCR).

Results
Overall, 23 patients were enrolled, of whom 21 completed preoperative therapy. Two patients achieved pCR (8.7%). pSTAT3 and IL-6/JAK/STAT3 signaling decreased in post-run-in biopsies of RUX-treated samples, while sustained treatment with RUX + PAC upregulated IL-6/JAK/STAT3 signaling compared to RUX alone. Both treatments decreased GZMB+ T cells implying immune suppression. RUX alone effectively inhibited JAK/STAT3 signaling but its combination with PAC led to incomplete inhibition. The immune suppressive effects of RUX alone and in combination may negate its growth inhibitory effects on cancer cells.

Conclusion
In summary, the use of RUX in TN-IBC was associated with a decrease in pSTAT3 levels despite lack of clinical benefit. Cancer cell-specific-targeting of JAK2/STAT3 or combinations with immunotherapy may be required for further evaluation of JAK2/STAT3 signaling as a cancer therapeutic target.

Trial registration
www.clinicaltrials.gov, NCT02876302. Registered 23 August 2016.
BORIS/CTCFL epigenetically reprograms clustered CTCF binding sites into alternative transcriptional start sites
Authors: Pugacheva Elena M. , Bhatt Dharmendra Nath , Rivero-Hinojosa Samuel , Tajmul Md , Fedida Liron , Price Emma , Ji Yon , Loukinov Dmitri , Strunnikov Alexander V. , Ren Bing , Lobanenkov Victor V. 
Published: January 2024

Abstract
Background
Pervasive usage of alternative promoters leads to the deregulation of gene expression in carcinogenesis and may drive the emergence of new genes in spermatogenesis. However, little is known regarding the mechanisms underpinning the activation of alternative promoters.

Results
Here we describe how alternative cancer-testis-specific transcription is activated. We show that intergenic and intronic CTCF binding sites, which are transcriptionally inert in normal somatic cells, could be epigenetically reprogrammed into active de novo promoters in germ and cancer cells. BORIS/CTCFL, the testis-specific paralog of the ubiquitously expressed CTCF, triggers the epigenetic reprogramming of CTCF sites into units of active transcription. BORIS binding initiates the recruitment of the chromatin remodeling factor, SRCAP, followed by the replacement of H2A histone with H2A.Z, resulting in a more relaxed chromatin state in the nucleosomes flanking the CTCF binding sites. The relaxation of chromatin around CTCF binding sites facilitates the recruitment of multiple additional transcription factors, thereby activating transcription from a given binding site. We demonstrate that the epigenetically reprogrammed CTCF binding sites can drive the expression of cancer-testis genes, long noncoding RNAs, retro-pseudogenes, and dormant transposable elements.

Conclusions
Thus, BORIS functions as a transcription factor that epigenetically reprograms clustered CTCF binding sites into transcriptional start sites, promoting transcription from alternative promoters in both germ cells and cancer cells.
Angiosarcoma of gallbladder, a literature review
Authors: Salehi Mahsa , Rehman Shafi , Davis Sissmol , Jafari Hamid Reza 
Published: January 2024

Abstract
Background
Angiosarcoma of the gallbladder is a rare diagnostic entity rarely encountered by pathologists and has rarely been reported in literature. This review aimed to examine the clinicopathological features, immunohistochemistry, treatment, and outcomes of gallbladder angiosarcoma.

Methods
A search of the PubMed, Science Direct and Google Scholar was done with the search terms ("angiosarcoma" OR "angiosarcomas") AND ("gallbladder" OR "gallbladders"). Based on inclusion and exclusion criteria, only case reports could be used for this review.

Result
8 case reports were chosen in the end for analysis. The mean age of the patients at presentation was 65 years. It was most frequently observed in males. Abdominal pain and palpable mass were the most commonly reported symptoms. Cholelithiasis and anemia were also reported. On histopathology morphologically epithelioid appearance of angiosarcoma was evident. Cytokeratin (CK) AE1/AE3, Von willebrand factor, Factor VIII antigen, Vimentin, CD31 were positive. Meanwhile, UEA, CD34, CD117, S-100, Keratin, EMA, and CEA showed negative outcome. Surgery was the preferred method of treatment and a mean 10-months follow-up was done.

Conclusion
Despite the unavailability of convincing data, histological and immunohistochemical analyses play a major role in the diagnosis of gallbladder angiosarcoma. Nevertheless, more comprehensive clinical studies are required to provide universal guidelines for the treatment and diagnosis of angiosarcoma of the gallbladder.
A hybrid foresight study of the environmental reference laboratory system in Finland: a foresight study for the Government of Finland
Authors: Myllylä Yrjö , Kaivo-oja Jari 
Published: January 2024

AbstractThis article presents a hybrid foresight study using the Delphi methodology. The study is part of a strategic research project of the Finnish state named “Foresight in Environmental Reference Laboratory Operations.” The main starting point for this study was the Policy Delphi method, which was supplemented with other Delphi variants and decision support methods. In this hybrid foresight application, Delphi methodology was combined with decision-making and strategic planning tools, namely (1) SWOT analysis, (2) Boston Consulting Group Matrix, (3) research infrastructure (RI) analysis, (4) platform analysis, and (5) integrative foresight workshop. This article draws strongly on the hybrid foresight methodology perspective of foresight tool orchestration. The authors argue that the Delphi methodology gains reliability and appeal with hybrid methodological orchestration. The function of reference laboratories includes services for the verification and maintenance of the quality and validity of environmental measurements, such as the maintenance of reference measurement equipment, expertise, and training, and the organization of national reference measurements as well as participation in international reference measurements, method development, and standardization. The study shows the importance of environmental reference laboratories addressing the following challenges by 2030: (1) new measurement targets, such as the diffusion of nanomaterials, microplastics, and drugs in both nature and the food chain and the environmental impact of recycled materials and indoor air issues; (2) automation of measurement activities and transition to technologically advanced measurement systems; (3) citizens’ opportunities to participate in the production of information about their environment through new technologies; (4) preparing for the incorporation and internationalization of laboratory operations; and (5) the concentration of measurement service business.
Vacuum-assisted closure for chest wall reconstruction infection caused by Streptococcus mitis after surgery of lung cancer: a case report
Authors: Motono Nozomu , Mizoguchi Takaki , Ishikawa Masahito , Iwai Shun , Iijima Yoshihito , Uramoto Hidetaka 
Published: January 2024

Abstract
Background
Among a cohort of patients who underwent chest wall resection and reconstruction by rigid prosthesis, 6% required removal of the prosthesis, and in 80% of these cases the indication for prosthesis removal was infection. Although artificial prosthesis removal is the primary approach in such cases of infection, the usefulness of vacuum-assisted closure (VAC) has also been reported.

Case presentation
A 64-year-old man with diabetes mellitus underwent right middle and lower lobectomy with chest wall (3rd to 5th rib) resection and lymph node dissection because of lung squamous cell carcinoma. The chest wall defect was reconstructed by an expanded polytetrafluoroethylene (PTFE) sheet. Three months after surgery, the patient developed an abscess in the chest wall around the PTFE sheet. We performed debridement and switched to VAC therapy 2 weeks after starting continuous drainage of the abscess in the chest wall. The space around the PTFE sheet gradually decreased, and formation of wound granulation progressed. We performed wound closure 6 weeks after starting VAC therapy, and the patient was discharged 67 days after hospitalization.

Conclusions
We experienced a case of chest wall reconstruction infection after surgery for non-small cell lung cancer that was successfully treated by VAC therapy without removal of the prosthesis. Although removal of an infectious artificial prosthesis can be avoided by application of VAC therapy, perioperative management to prevent surgical site infection is considered essential.
Cardiovascular risk in elderly Egyptians with myelodysplastic syndromes
Authors: Efat Alaa , Shoeib Sabry , Abdelfattah Raafat , Alaa-Eldeen Faten , Ramadan Shrief , ElKholy Aly , Wahb Rana 
Published: January 2024

Abstract
Background
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell-derived disorders manifested by cytopenias peripherally. MDS initiates an inflammatory process which lead to atherosclerosis. Patients with MDS have 1.5-fold higher risks of cardiovascular risks.

Objective
Evaluation of cardiovascular risk and unraveling the possible correlation of carotid intima media thickness (CIMT) with clinical, hematologic, and laboratory variables in elderly patients with MDS.

Methods
We conducted a case–control research on 168 participants to elicit the serum level of homocysteine, serum high-sensitive C-reactive protein (Hs-CRP), and CIMT in relation to cardiovascular risk, 84 of whom had MDS diagnoses. From March 2021 to the end of May 2023, we chose them among the inpatients and outpatients of the Menoufia University Hospitals’ Clinical Hematology Division. We contrasted the chosen MDS patients with 84 healthy individuals as controls.

Results
Right and left CIMT were significantly higher in MDS patients than controls as well as for lipid profile, blood pressure, blood sugar, and Hs-CRP. Homocysteine was higher in MDS patients but of no statistical significance.

Conclusion
As CIMT and C-reactive protein level were significantly higher in studied patients, we may consider MDS group of patients to have higher risk for cardiovascular disease than normal people.
5-Hydroxymethylcytosine Profiling of Cell-Free DNA Identifies Bivalent Genes That Are Prognostic of Survival in High-Risk Neuroblastoma
Authors: Chennakesavalu Mohansrinivas , Moore Kelley , Chaves Gepoliano , Veeravalli Sahil , TerHaar Rachel , Wu Tong , Lyu Ruitu , Chlenski Alexandre , He Chuan , Piunti Andrea , Applebaum Mark A. 
Published: January 2024

PURPOSE Neuroblastoma is the most common extracranial solid tumor in childhood. We previously showed that circulating cell-free DNA (cfDNA) and tumor biopsy derived 5-hydroxymethylcytosime (5-hmC) profiles identified patients with neuroblastoma who experienced subsequent relapse. Here, we hypothesized that 5-hmC modifications selectively enriched in cfDNA compared with tumor biopsy samples would identify epigenetic changes associated with aggressive tumor behavior and identify novel biomarkers of outcome in patients with high-risk neuroblastoma. METHODS 5-hmC profiles from cfDNA (n = 64) and tumor biopsies (n = 48) were compared. Two neuroblastoma cell lines underwent chromatin immunoprecipitation followed by sequencing (ChIP-Seq) for H3K27me3, H3K4me3, and H3K27ac; kethoxal-associated single-stranded DNA sequencing; hmC-Seal for 5-hmC; and RNA-sequencing (RNA-Seq). Genes enriched for both H3K27me3 and H3K4me3 in the included cell lines were defined as bivalent. Using bivalent genes defined in vitro, a bivalent signature was established in three publicly available cohorts of patients with neuroblastoma through gene set variation analysis. Differences between tumors with high or low bivalent signatures were assessed by the Kaplan-Meier method and Cox proportional hazards models. RESULTS In cfDNA compared with tumor biopsy derived 5-hmC profiles, we found increased 5-hmC deposition on Polycomb Repressive Complex 2 target genes, a finding previously described in the context of bivalent genes. We identified 313 genes that bore bivalent chromatin marks, were enriched for mediators of neuronal differentiation, and were transcriptionally repressed across a panel of heterogeneous neuroblastoma cell lines. In three distinct clinical cohorts, low bivalent signature was significantly and independently associated with worse clinical outcome in patients with high-risk neuroblastoma. CONCLUSION Low expression of bivalent genes is a biomarker of worse outcome in patients with high-risk neuroblastoma.
High Neuraxial Block in Obstetrics: A 2.5-Year Nationwide Surveillance Approach in the Netherlands
Authors: Beenakkers Ingrid C. M. , Schaap Timme P. , van den Bosch Oscar F. C. 
Published: January 2024

BACKGROUND:
High neuraxial block is a rare but serious adverse event in obstetric anesthesia that can ultimately lead to respiratory insufficiency and cardiac arrest. Previous reports on its incidence are limited to populations in the United Kingdom and the United States. Little is known about the incidence and clinical features of high neuraxial block in the Netherlands, where the presence of anesthesiologists in the labor and delivery unit is comparatively lower. We aimed to assess the incidence and clinical features of high neuraxial block in obstetrics and to formulate ways to improve obstetric anesthesia on a national level.

METHODS:
This nationwide, prospective, population-based cohort study was designed to identify cases of high neuraxial block requiring ventilatory support (with supraglottic airway device or tracheal intubation) or cardiopulmonary resuscitation between November 2019 and May 2022. Cases were prospectively collected using the Netherlands Obstetric Surveillance System (NethOSS) in all hospitals with a maternity unit. Complete case file copies were obtained to determine risk factors and clinical course.

RESULTS:
During the study period, 5 cases of high neuraxial block requiring tracheal intubation were identified. The estimated incidence of high neuraxial block requiring tracheal intubation was 1 in 29,770 neuraxial procedures in labor (95% confidence interval, 1:12,758–1:91,659). Three of 5 identified cases occurred in the operating room after single-shot spinal anesthesia for Cesarean delivery after epidural analgesia in labor. One case developed in the labor ward due to an inadvertent intrathecal or subdural catheter placed for labor analgesia. The fifth case followed single-shot spinal anesthesia for elective Cesarean delivery. All 5 patients were successfully extubated in the operating room after Cesarean delivery, without the need for intensive care admission. There were no cardiac arrests and no neonatal deaths.

CONCLUSIONS:
High neuraxial block requiring tracheal intubation is a rare but impactful complication in obstetric anesthesia, potentially affecting both mother and fetus. Spinal anesthesia after epidural analgesia in labor is a common cause of high neuraxial block. Meticulous follow-up of epidurals in labor facilitates conversion to surgical anesthesia and may therefore reduce the need for spinal anesthesia after epidural analgesia. Large-scale surveillance systems in obstetric anesthesia are needed to identify those at risk, as well as to formulate further strategies to mitigate this burden.