bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unilateral ovarian recurrence 5 years after hysterectomy for microinvasive squamous cervical cancer stage IA1: a rare case report
Authors: Tong Longxia , Wu Lin 
Published: July 2023

Abstract
Background
Ovarian metastasis or recurrence of cervical microinvasive squamous cell carcinoma (SCC) is very rare. We report a case of unilateral ovarian recurrence 5 years after hysterectomy for the SCC stage IA1 without lymph vascular space invasion (LVSI).

Case presentation
A 49-year-old female patient suffered from a dull pain in the left lower abdomen for 3 months. And five years ago, she received a laparoscopic hysterectomy for the treatment of stage IA1 (without LVSI) SCC of the cervix. The level of squamous cell carcinoma antigen (SCC-Ag) in serum was significantly elevated (10.60 ng/mL). Pelvic magnetic resonance imaging (MRI) revealed a left ovarian solid tumor measuring 5.5 × 3.9 × 5.6 cm with heterogeneous enhancement. During laparotomy, the left ovarian tumor was measured about 5.0 × 4.5 × 3.0 cm and seemed densely adherent to the posterior peritoneal wall, including the left ureter. The tumor and pelvic lymph node were carefully removed. Postoperative anatomy revealed a solid mass with a greyish-white section. Postoperative pathology showed recurrent moderately differentiated ovarian SCC with negative pelvic lymph nodes. Immunohistochemistry showed that the tumor cells were positive for P16, P63, P40, and CK5/6 markers, and the positive rate of Ki67 was about 80%.

Conclusions
Ovary preservation is reasonable and appropriate in young patients with microinvasive SCC. Ovarian recurrence is rare, but gynecological oncologists should not overlook its possibility. The serum SCC-Ag is an important indicator for monitoring postoperative disease progression.
Phase 1 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1-related unresectable plexiform neurofibromas
Authors: Hu Xiaojie , Li Wenbin , Zeng Kang , Xu Zhongyuan , Li Changxing , Kang Zhuang , Li Shenglan , Huang Xin , Han Pu , Lin Hongmei , Hui Ai-Min , Tan Yan , Diao Lei , Li Ben , Wang Xingli , Wu Zhuli , Lin Xiaoxi 
Published: July 2023

Abstract
Background
Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN.

Methods
This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles.

Results
Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing.

Conclusions
FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication.

Trial registration
ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.
Identification of a novel compound heterozygous mutation and a homozygous mutation of SLURP1 in Chinese families with Mal de Meleda
Authors: Wang Tian , Tang Zhuangli , Xiao Tong , Ren Junru , He Shuyao , Liu Yan , Xiao Shengxiang , Wang Xiaopeng 
Published: July 2023

Abstract
Background
Mal de Meleda is an autosomal recessive palmoplantar keratoderma, with SLURP1 identified as the pathogenic gene responsible. Although over 20 mutations in SLURP1 have been reported, only the mutation c.256G > A (p.G87R) has been detected in Chinese patients. Here, we report a novel heterozygous SLURP1 mutation in a Chinese family.

Methods
We assessed the clinical manifestations of two Chinese patients with Mal de Meleda and collected specimens from the patients and other family members for whole-exome and Sanger sequencing. We used algorithms (MutationTaster, SIFT, PolyPhen-2, PROVEAN, PANTHER, FATHMM, mCSM, SDM and DUET) to predict the pathogenetic potential of the mutation detected. We also employed AlphaFold2 and PyMOL for protein structure analysis.

Results
Both patients displayed the typical manifestation of palmoplantar keratoderma. In Proband 1, we detected a novel compound heterozygous mutation (c.243C > A and c.256G > A) in exon 3 of SLURP1. Proband 2 was an adult female born to a consanguineous family and carried a homozygous mutation (c.211C > T). Algorithms indicated both mutations to be probably disease causing. We used AlphaFold2 to predict the protein structure of these mutations and found that they cause instability, as shown by PyMOL.

Conclusions
Our study identified a novel compound heterozygous mutation (c.243C > A and c.256G > A) in a Chinese patient with Mal de Meleda that has the potential to cause instability in protein structure. Moreover, this study expands on the existing knowledge of SLURP1 mutations and contributes to knowledge of Mal de Meleda.
Genomic and transcriptional characterization of early esophageal squamous cell carcinoma
Authors: Zhao Jingjing , Jia Xiya , Li Qiaojuan , Zhang Hena , Wang Jianjun , Huang Shenglin , Hu Zhixiang , Li Caiping 
Published: July 2023

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is a highly heterogeneous cancer that lacks comprehensive understanding and effective treatment. Although multi-omics study has revealed features and underlying drivers of advanced ESCC, research on molecular characteristics of the early stage ESCC is quite limited.

Materials and methods
We presented characteristics of genomics and transcriptomics in 10 matched pairs of tumor and normal tissues of early ESCC patients in the China region.

Results
We identified the specific patterns of cancer gene mutations and copy number variations. We also found a dramatic change in the transcriptome, with more than 4,000 genes upregulated in cancer. Among them, more than one-third of HOX family genes were specifically and highly expressed in early ESCC samples of China and validated by RT-qPCR. Gene regulation network analysis indicated that alteration of Hox family genes promoted the proliferation and metabolism remodeling of early ESCC.

Conclusions
We characterized the genomic and transcriptomic landscape of 10 paired normal adjacent and early ESCC tissues in the China region, and provided a new perspective to understand the development of ESCC and insight into potential prevention and diagnostic targets for the management of early ESCC in China.
Enrichment strategies to enhance genome editing
Authors: Mikkelsen Nanna S. , Bak Rasmus O. 
Published: July 2023

AbstractGenome editing technologies hold great promise for numerous applications including the understanding of cellular and disease mechanisms and the development of gene and cellular therapies. Achieving high editing frequencies is critical to these research areas and to achieve the overall goal of being able to manipulate any target with any desired genetic outcome. However, gene editing technologies sometimes suffer from low editing efficiencies due to several challenges. This is often the case for emerging gene editing technologies, which require assistance for translation into broader applications. Enrichment strategies can support this goal by selecting gene edited cells from non-edited cells. In this review, we elucidate the different enrichment strategies, their many applications in non-clinical and clinical settings, and the remaining need for novel strategies to further improve genome research and gene and cellular therapy studies.
EEG-based emergency braking intention detection during simulated driving
Authors: Liang Xinbin , Yu Yang , Liu Yadong , Liu Kaixuan , Liu Yaru , Zhou Zongtan 
Published: July 2023

Abstract
Background
Current research related to electroencephalogram (EEG)-based driver’s emergency braking intention detection focuses on recognizing emergency braking from normal driving, with little attention to differentiating emergency braking from normal braking. Moreover, the classification algorithms used are mainly traditional machine learning methods, and the inputs to the algorithms are manually extracted features.

Methods
To this end, a novel EEG-based driver’s emergency braking intention detection strategy is proposed in this paper. The experiment was conducted on a simulated driving platform with three different scenarios: normal driving, normal braking and emergency braking. We compared and analyzed the EEG feature maps of the two braking modes, and explored the use of traditional methods, Riemannian geometry-based methods, and deep learning-based methods to predict the emergency braking intention, all using the raw EEG signals rather than manually extracted features as input.

Results
We recruited 10 subjects for the experiment and used the area under the receiver operating characteristic curve (AUC) and F1 score as evaluation metrics. The results showed that both the Riemannian geometry-based method and the deep learning-based method outperform the traditional method. At 200 ms before the start of real braking, the AUC and F1 score of the deep learning-based EEGNet algorithm were 0.94 and 0.65 for emergency braking vs. normal driving, and 0.91 and 0.85 for emergency braking vs. normal braking, respectively. The EEG feature maps also showed a significant difference between emergency braking and normal braking. Overall, based on EEG signals, it was feasible to detect emergency braking from normal driving and normal braking.

Conclusions
The study provides a user-centered framework for human–vehicle co-driving. If the driver's intention to brake in an emergency can be accurately identified, the vehicle's automatic braking system can be activated hundreds of milliseconds earlier than the driver's real braking action, potentially avoiding some serious collisions.
Preventive strategies for hypercoagulation in Cushing’s syndrome: when and how
Authors: Lopes Valentim , Marques Olinda , De Sousa Lages Adriana 
Published: July 2023

Abstract
Purpose
The endogenous hypercortisolism that characterizes Cushing’s syndrome (CS) is associated with a state of hypercoagulability that significantly increases the risk of thromboembolic disease, especially, venous events. Despite this certainty, there is no consensus on the best thromboprophylaxis strategy (TPS) for these patients. Our aim was to summarize the published data about different thromboprophylaxis strategies, and to review available clinical tools assisting thromboprophylaxis decision making.

Methods
Narrative review of thromboprophylaxis strategies in patients with Cushing’s syndrome. A search was carried out on PubMed, Scopus and EBSCO until November 14th, 2022, and articles were selected based on their relevance and excluded in case of redundant content.

Results
Literature is scarce regarding thromboprophylaxis strategies to be adopted in the context of endogenous hypercortisolism, most often being a case-by-case decision according to the centre expertise. Only three retrospective studies, with a small number of patients enrolled, evaluated the use of hypocoagulation for the thromboprophylaxis of patients with CS in the post-operative period of transsphenoidal surgery and/or adrenalectomy, but all of them with favourable results. The use of low molecular weight heparin is the most frequent option as TPS in CS context. There are numerous venous thromboembolism risk assessment scores validated for different medical purposes, but just one specifically developed for CS, that must be validated to ensure solid recommendations in this context. The use of preoperative medical therapy is not routinely recommended to decrease the risk of postoperative venous thromboembolic events. The peak of venous thromboembolic events occurs in the first three months post-surgery.

Conclusion
The need to hypocoagulate CS patients, mainly in the post-operative period of a transsphenoidal surgery or an adrenalectomy, is undoubtable, especially in patients with an elevated risk of venous thromboembolic events, but the precise duration and the hypocoagulation regimen to institute is yet to be determined with prospective studies.
Whole genome sequence analysis of CPV-2 isolates from 1998 to 2020
Authors: Sarabandi Sajed , Pourtaghi Hadi 
Published: July 2023

AbstractCanine parvovirus-2 (CPV-2) is a virus with worldwide spread causing canine gastroenteritis. New strains of this virus have unique characteristics and are resistant to some vaccine strains. Therefore, understanding the root causes of resistance has proven to be of increasing concern to many scientists. This study collected 126 whole genome sequences of CPV-2 subtypes with specific collection dates from the NCBI data bank. The whole genome sequences of CPV-2 collected from different countries were analyzed to detect the new substitutions and update these mutations. The result indicated 12, 7, and 10 mutations in NS1, VP1, and VP2, in that respective order. Moreover, the A5G and Q370R mutations of VP2 are the most common changes in the recent isolates of the CPV-2C subtype, and the new N93K residue of VP2 is speculated to be the cause of vaccine failure. To summarize, the observed mutations, which are increasing over time, causes several changes in viral characteristic. A comprehensive understanding of these mutations can lead us to control potential future epidemics associated with this virus more efficiently.
β1 integrin is essential for blood–brain barrier integrity under stable and vascular remodelling conditions; effects differ with age
Authors: Halder Sebok K. , Delorme-Walker Violaine D. , Milner Richard 
Published: July 2023

Abstract
Background
Maintaining a tight blood–brain barrier (BBB) is an important prerequisite for the preservation of neurological health, though current evidence suggests it declines with age. While extracellular matrix-integrin interactions play critical roles in regulating the balance between vascular stability and remodeling, it remains to be established whether manipulation of integrin function weakens or strengthens vascular integrity. Indeed, recent reports have generated conflicting outcomes in this regard.

Methods
Here, in young (8–10 weeks) and aged (20 months) mice, we examined the impact of intraperitoneal injection of a function-blocking β1 integrin antibody, both under normoxic conditions, when the BBB is stable, and during chronic mild hypoxic (CMH; 8% O2) conditions, when a vigorous vascular remodeling response is ongoing. Brain tissue was examined by immunofluorescence (IF) for markers of vascular remodeling and BBB disruption, and microglial activation and proliferation. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison post-hoc test.

Results
In both young and aged mice, β1 integrin block greatly amplified hypoxia-induced vascular disruption, though it was much less under normoxic conditions. Interestingly, under both normoxic and hypoxic conditions, β1 integrin antibody-induced BBB disruption was greater in young mice. Enhanced BBB breakdown was associated with increased levels of the leaky BBB marker MECA-32 and with greater loss of endothelial tight junction proteins and the adherens protein VE-cadherin. Surprisingly, β1 integrin blockade did not reduce hypoxia-induced endothelial proliferation, nor did it prevent the hypoxia-associated increase in vascularity. Commensurate with the increased vascular disruption, β1 integrin blockade enhanced microglial activation both in young and aged brain, though the impact was much greater in young brain. In vitro studies revealed that β1 integrin blockade also reduced the integrity of a brain endothelial monolayer and triggered disruptions in tight junction proteins.

Conclusions
These data demonstrate that β1 integrin plays an essential role in maintaining BBB integrity, both under stable normoxic conditions and during hypoxia-induced vascular remodeling. As β1 integrin blockade had a greater disruptive effect in young brain, effectively shifting the BBB phenotype of young brain towards that of the aged, we speculate that enhancing β1 integrin function at the aged BBB may hold therapeutic potential by reverting the deteriorating BBB phenotype back towards that of the young.
Identifying and addressing patient substance use: a survey of chiropractic clinicians
Authors: Gliedt Jordan A. , Reynolds Maureen , Moonaz Steffany , Long Cynthia R. , Russell Robb , Schneider Michael J. 
Published: July 2023

Abstract
Background
Chiropractors commonly encounter patients who present for spine pain with parallel substance use. There is currently no widespread training within the chiropractic profession to prepare chiropractors to recognize and address substance use in clinical practice. The purpose of this study was to examine chiropractors’ confidence, self-perceptions, and interest in education associated with identifying and addressing patient substance use.

Methods
A 10-item survey was developed by the authors. The survey addressed chiropractors’ assessment of their training, experiences, and educational interest/needs regarding identifying and addressing patient substance use. The survey instrument was uploaded to Qualtrics and was electronically distributed to chiropractic clinicians at active and accredited English-speaking Doctor of Chiropractic degree programs (DCPs) in the United States.

Results
A total of 175 individual survey responses were returned from a total of 276 eligible participants (63.4% response rate) from 16 out of 18 active and accredited English-speaking DCPs (88.8% of DCPs) in the United States. Nearly half of respondents strongly disagreed or disagreed (n = 77, 44.0%) that they were confident in their ability to identify patients who misuse prescription medication. The majority of respondents (n = 122, 69.7%) indicated that they did not have an established referral relationship with local clinical providers who provide treatment for individuals who use drugs or misuse alcohol or prescription medications. Most respondents strongly agreed or agreed (n = 157, 89.7%) that they would benefit from participating in a continuing education course on topics related to patients who use drugs or misuse alcohol or prescription medications.

Conclusions
Chiropractors indicated a need for training to help them identify and address patient substance use. There is a demand among chiropractors to develop clinical care pathways for chiropractic referrals and collaboration with health care professionals who provide treatment for individuals who use drugs or misuse alcohol or prescription medications.
Guided blood transfusion of trauma patients with rotational thromboelastometry: a single-center cohort study
Authors: Salehi Mina , Bola Rajan , de Jong Nenke , Shih Andrew W. , Garraway Naisan , Dawe Philip 
Published: July 2023

Abstract
Background
Rotational thromboelastometry (ROTEM) is a blood test used to measure in vitro clot strength as a surrogate for a patient’s ability to form clots in vivo. This provides information about induction, formation, and clot lysis, allowing goal-directed transfusion therapy for specific hemostatic needs. We sought to evaluate the effect of ROTEM-guided transfusion on blood product usage and in-hospital mortality among patients with a traumatic injury.

Methods
This was a single-center observational cohort analysis of emergency department patients in a Level 1 trauma center. We compared blood usage in trauma patients in whom ratio-based massive hemorrhage protocols were activated in the twelve months before the introduction of ROTEM (pre-ROTEM group) to the twelve months following the introduction of ROTEM (ROTEM-period group). ROTEM was implemented in this center in November 2016. The ROTEM device allowed clinicians to make real-time decisions about blood product therapy in resuscitation for trauma.

Results
The pre-ROTEM group contained 21 patients. Forty-three patients were included from the ROTEM-period, of whom 35 patients received ROTEM-guided resuscitation (81% compliance). The use of fibrinogen concentrate was significantly higher in the ROTEM-period group (pre-ROTEM mean 0.2 vs. ROTEM-period mean 0.8; p = 0.006). There was no significant difference in the number of units of red blood cells, platelets, cryoprecipitate, or fresh frozen plasma transfused between these groups. There was no significant difference in the mortality rate between the pre-ROTEM and ROTEM-period groups (33% vs. 19%; p = 0.22).

Conclusions
The introduction of ROTEM-guided transfusion at this institution was associated with increased fibrinogen usage, but this did not impact mortality rates. There was no difference in the administration of red blood cell, fresh frozen plasma, platelet, and cryoprecipitate. Future research should focus on increased ROTEM compliance and optimizing ROTEM-guided transfusion to prevent blood product overuse among trauma patients.
DNA methylation is differentially associated with glycemic outcomes by different types of weight-loss interventions: an epigenome-wide association study
Authors: Wen Xiaoxiao , Palma-Gudiel Helena , Miao Guanhong , Chen Mingjing , Huo Zhiguang , Peng Hao , Anton Stephen , Hu Gang , Brock Ricky , Brantley Phillip J. , Zhao Jinying 
Published: July 2023

Abstract
Background
Alterations in DNA methylation (DNAm) have been reported to be a mechanism by which bariatric surgeries resulted in considerable metabolic improvements. Previous studies have mostly focused on change in DNAm following weight-loss interventions, yet whether DNAm prior to intervention can explain the variability in glycemic outcomes has not been investigated. Here, we aim to examine whether baseline DNAm is differentially associated with glycemic outcomes induced by different types of weight-loss interventions.

Methods
Participants were 75 adults with severe obesity who underwent non-surgical intensive medical intervention (IMI), adjustable gastric band (BAND) or Roux-en-Y gastric bypass (RYGB) (n = 25 each). Changes in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were measured at 1-year after intervention. DNAm was quantified by Illumina 450 K arrays in baseline peripheral blood DNA. Epigenome-wide association studies were performed to identify CpG probes that modify the effects of different weight-loss interventions on glycemic outcomes, i.e., changes in FPG and HbA1c, by including an interaction term between types of intervention and DNAm. Models were adjusted for weight loss and baseline clinical factors.

Results
Baseline DNAm levels at 3216 and 117 CpGs were differentially associated with changes in FPG and HbA1c, respectively, when comparing RYGB versus IMI. Of these, 79 CpGs were significant for both FPG and HbA1c. The identified genes are enriched in adaptive thermogenesis, temperature homeostasis and regulation of cell population proliferation. Additionally, DNAm at 6 CpGs was differentially associated with changes in HbA1c when comparing RYGB versus BAND.

Conclusions
Baseline DNAm is differentially associated with glycemic outcomes in response to different types of weight-loss interventions, independent of weight loss and other clinical factors. Such findings provided initial evidence that baseline DNAm levels may serve as potential biomarkers predictive of differential glycemic outcomes in response to different types of weight-loss interventions.