bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of transcriptomic profiling of 5‐methylcytosin modification in placentas from preeclampsia and normotensive pregnancies
Authors: Wei Xiaohong , Zhou Shengping , Liao Lingyun , Liu Min , Gao Yijie , Yin Yangxue , Xu Qin , Zhou Rong 
Published: January 2023

AbstractIncreasing evidence suggests that RNA m5C modification and its regulators have been confirmed to be associated with the pathogenesis of many diseases. However, the distribution and biological functions of m5C in mRNAs of placental tissues remain unknown. we collected placentae from normotensive pregnancies (CTR) and preeclampsia patients (PE) to analyze the transcriptomic profiling of m5C RNA methylation through m5C RNA immunoprecipitation (UMI‐MeRIP‐Seq). we discovered that overall m5C methylation peaks were decreased in placental tissues from PE patients. And, 2844 aberrant m5C peaks were identified, of which respectively 1304 m5C peaks were upregulated and 1540 peaks were downregulated. The distribution of m5C peaks were mainly located in CDS (coding sequences) regions in placental tissues of both groups, but compared with the CTR group, the m5C peak in PE group before the stop code of CDS was significantly increased and even higher than the peak value after start code in CDS. Differentially methylated genes were mainly enriched in MAPK/cAMP signaling pathway. Moreover, the up‐regulated genes with hypermethylated modification were enriched in the processes of hypoxia, inflammation/immune response. Finally, through analyzing the mRNA expression levels of m5C RNA methylation regulators, we found only DNMT3B and TET3 were significantly upregulated in PE samples than in control group. And they are not only negatively correlated with each other, but also closely related to those differentially expressed genes modified by differential methylation.Our findings provide new insights regarding alterations of m5C RNA modification into the pathogenic mechanisms of PE.
Neuroprotective effects of melatonin‐mediated mitophagy through nucleotide‐binding oligomerization domain and leucine‐rich repeat‐containing protein X1 in neonatal hypoxic–ischemic brain damage
Authors: Zhang Yi , Chen Dan , Wang Yiwei , Wang Xingzao , Zhang Zhong , Xin Ying 
Published: January 2023

AbstractHypoxia–ischemia (HI) is a major cause of brain damage in neonates. Mitochondrial dysfunction acts as a hub for a broad spectrum of signaling events, culminating in cell death triggered by HI. A neuroprotective role of melatonin (MT) has been proposed, and mitophagy regulation seems to be important for cell survival. However, the molecular mechanisms underlying MT‐mediated mitophagy during HI treatment are poorly defined. Nucleotide‐binding oligomerization domain and leucine‐rich repeat‐containing protein X1 (NLRX1) has emerged as a critical regulator of mitochondrial dynamics and neuronal death that participates in the pathology of diverse diseases. This study aimed to clarify whether NLRX1 participates in the regulation of mitophagy during MT treatment for hypoxic–ischemic brain damage (HIBD). We demonstrated that MT protected neonates from HIBD through NLRX1‐mediated mitophagy in vitro and in vivo. Meanwhile, MT upregulated the expression of NLRX1, Beclin‐1, and autophagy‐related 7 (ATG7) but decreased the expression of the mammalian target of rapamycin (mTOR) and translocase of the inner membrane of mitochondrion 23 (TIM23). Moreover, the neuroprotective effects of MT were abolished by silencing NLRX1 after oxygen–glucose deprivation (OGD). In addition, the downregulation of mTOR and upregulation of Beclin‐1 and ATG7 by MT were inhibited after silencing NLRX1 under OGD. In summary, MT modulates mitophagy induction through NLRX1 and plays a protective role in HIBD, providing insight into potential therapeutic targets for MT to exert neuroprotection.
Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study
Authors: Kuck Kai , Naik Bhiken I. , Domino Karen B. , Posner Karen L. , Saager Leif , Stuart Ami R. , Johnson Ken B. , Alpert Salome B. , Durieux Marcel E. , Sinha Anik K. , Brummett Chad M. , Aziz Michael F. , Cummings Kenneth C. , Gaudet John G. , Kurz Andrea , Rijsdijk Mienke , Wanderer Jonathan P. , Pace Nathan L. ,   the Multicenter Perioperative Outcomes Group Enhanced Observation Study Investigator Group for the Multicenter Perioperative Outcomes Group Enhanced Observation Study Collaborator Group
Published: January 2023

Background
There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery.

Methods
Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed.

Results
Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively.

Conclusions
Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Noninvasive Skin Autofluorescence of Advanced Glycation End Products for Detecting Ossification of the Posterior Longitudinal Ligament in the Thoracic Spine
Authors: Doi Toru , Horii Chiaki , Tozawa Keiichiro , Nakarai Hiroyuki , Sasaki Katsuyuki , Yoshida Yuichi , Ito Yusuke , Ohtomo Nozomu , Sakamoto Ryuji , Nakajima Koji , Nagata Kosei , Okamoto Naoki , Nakamoto Hideki , Kato So , Taniguchi Yuki , Matsubayashi Yoshitaka , Tanaka Sakae , Oshima Yasushi 
Published: January 2023

Study Design.
A single-center prospective observational study.

Objective.
The aim was to clarify the usefulness of assessing advanced glycation end products (AGEs) by noninvasive skin autofluorescence in patients with ossification of the posterior longitudinal ligament (OPLL).

Summary of Background Data.
AGE accumulation is associated with various systemic disorders, including aging, diabetes mellitus, and obesity. AGEs have also been associated with OPLL, but their assessment by noninvasive skin autofluorescence has not been yet studied in these patients.

Materials and Methods.
We enrolled patients with degenerative spinal spondylosis and divided them into non-OPLL and OPLL groups. The OPLL group was further subdivided into cervical OPLL (C-OPLL) and thoracic OPLL (T-OPLL) groups. We compared patients’ characteristics, serum laboratory data (i.e. hemoglobin A1c, total cholesterol, creatinine, and estimated glomerular filtration rate), and the skin autofluorescence intensity of AGEs (the AGE score) between the non-OPLL and OPLL groups and among the non-OPLL, C-OPLL, T-OPLL groups. Finally, the association of the AGE score with the presence of C-OPLL or T-OPLL was assessed by multinomial logistic regression.

Results.
Among the 240 eligible patients, 102 were in the non-OPLL group and 138 were in the OPLL group (92 with C-OPLL and 46 with T-OPLL). We observed no significant difference in the AGE score between the non-OPLL and OPLL groups, but when comparing the score among the non-OPLL, C-OPLL, and T-OPLL groups, we found that the T-OPLL group had a significantly higher AGE score. The results of multinomial regression analysis showed that a higher AGE score was significantly associated with T-OPLL (odds ratio: 1.46; 95% CI: 1.01–2.11; P=0.044).

Conclusion.
The AGE score determined by noninvasive skin autofluorescence could help to screen for OPLL in the thoracic spine.
Ambulatory Lumbar Fusion
Authors: Subramanian Tejas , Araghi Kasra , Sivaganesan Ahilan , Shahi Pratyush , Vaishnav Avani , Iyer Sravisht , Qureshi Sheeraz A. 
Published: January 2023

Study Design/Setting.
Systematic review.

Objective.
The primary purpose was to propose patient selection criteria and perioperative best practices that can serve as a starting point for an ambulatory lumbar fusion program. The secondary purpose was to review patient-reported outcomes (PROs) after ambulatory lumbar fusion.

Summary of Background.
As healthcare costs rise, there is an increasing emphasis on cost saving strategies (i.e. outpatient/ambulatory surgeries). Lumbar fusion procedures remain a largely inpatient surgery. Early studies have shown that fusion procedures can be safely preformed in an outpatient setting but no review has summarized these findings and best practices.

Materials and Methods.
This study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed/MEDLINE, The Cochrane Library, and Embase were searched. The following data were collected: (1) study design; (2) number of participants; (3) patient population; (4) procedure types; (5) procedure setting; (6) inclusion criteria; (7) protocols; (8) adverse events; (9) PROs; and (10) associations between patient/surgical factors, setting, and outcomes.

Results.
The search yielded 20 publications. The following selection criteria for ambulatory lumbar fusion were identified: age below 70, minimal comorbidities, low/normal body mass index, no tobacco use, and no opioid use. The perioperative protocol can include a multimodal analgesic regimen. The patient should be observed for at least three hours after surgery. The patient should not be discharged without an alertness check and a neurological examination. Patients experienced significant improvements in PROs after ambulatory lumbar fusion; similarly, when compared to an inpatient group, ambulatory lumbar fusion patients experienced a comparable or superior improvement in PROs.

Conclusion.
There are two critical issues surrounding ambulatory lumbar fusion: (1) Who is the ideal patient, and (2) What needs to be done to enable expedited discharge? We believe this review will provide a foundation to assist surgeons in making decisions regarding the performance of lumbar fusion on an ambulatory basis.

Level of Evidence.
Level III.
Differentiating Magnetic Resonance Images of Pyogenic Spondylitis and Spinal Modic Change Using a Convolutional Neural Network
Authors: Mukaihata Tomohito , Maki Satoshi , Eguchi Yawara , Geundong Kim , Shoda Junpei , Yokota Hajime , Orita Sumihisa , Shiga Yasuhiro , Inage Kazuhide , Furuya Takeo , Ohtori Seiji 
Published: January 2023

Study Design.
A retrospective analysis of magnetic resonance imaging (MRI).

Objective.
The study aimed to evaluate the performance of a convolutional neural network (CNN) to differentiate spinal pyogenic spondylitis from Modic change on MRI. We compared the performance of CNN to that of four clinicians.

Summary of Background Data.
Discrimination between pyogenic spondylitis and spinal Modic change is crucial in clinical practice. CNN deep-learning approaches for medical imaging are being increasingly utilized.

Methods.
We retrospectively reviewed MRIs from pyogenic spondylitis and spinal Modic change patients. There were 50 patients per group. Sagittal T1-weighted (T1WI), sagittal T2-weighted (T2WI), and short TI inversion recovery (STIR) MRIs were used for CNN training and validation. The deep learning framework Tensorflow was used to construct the CNN architecture. To evaluate CNN performance, we plotted the receiver operating characteristic curve and calculated the area under the curve. We compared the accuracy, sensitivity, and specificity of CNN diagnosis to that of a radiologist, spine surgeon, and two orthopedic surgeons.

Results.
The CNN-based area under the curves of the receiver operating characteristic curve from the T1WI, T2WI, and STIR were 0.95, 0.94, and 0.95, respectively. The accuracy of the CNN was significantly greater than that of the four clinicians on T1WI and STIR (P<0.05), and better than a radiologist and one orthopedic surgeon on the T2WI (P<0.05). The sensitivity was significantly better than that of the four clincians on T1WI and STIR (P<0.05), and better than a radiologist and one orthopedic surgeon on the T2WI (P<0.05). The specificity was significantly better than one orthopedic surgeon on T1WI and T2WI (P<0.05) and better than both orthopedic surgeons on STIR (P<0.05).

Conclusion.
We differentiated between Modic changes and pyogenic spondylitis using a CNN that interprets MRI. The performance of the CNN was comparable to, or better than, that of the four clinicians.
Cardiac Children Hospital Early Warning ScoreVersus the Inadequate Oxygen Delivery Index for the Detection of Early Warning Signs of Deterioration
Authors: Khalil Mujtaba , Abbas Qalab , Azhar Mohammad Kumael , Aamir Faiqa Binte , Hashmi Shiraz , Ali Sadaqat , Faiz Tahira , Malik Mahim Akmal 
Published: January 2023

OBJECTIVES:
To assess the utility of the Cardiac Children’s Hospital Early Warning Score (C-CHEWS) in the early detection of deterioration.

DESIGN:
Single-center longitudinal pilot study.

SETTING:
Pediatric cardiac ICU (PCICU), Aga Khan University.

INTERVENTIONS:
C-CHEWS and Inadequate Oxygen Delivery (IDO2) Index calculation every 2 hours.

PATIENTS:
A total of 60 children (0 d to 18 yr old).

MEASUREMENTS AND MAIN RESULTS:
A single-center longitudinal pilot study was conducted at PCICU. All postoperative extubated patients were assessed and scored between 0 and 11, and these scores were then correlated with the IDO2 index data available from the T3 platform. Adverse events were defined as a need for cardiopulmonary resuscitation, or reintubation, and death. A total of 920 C-CHEWS and IDO2 scores were analyzed on 60 patients during the study period. There were 36 males and 24 females, and the median age of the study population was 34 months (interquartile range, 9.0–72.0 mo). Fourteen patients (23.3%) developed adverse events; these included 9 reintubations and 5 cardiopulmonary arrests, resulting in 2 deaths. The area under the curve (AUC) for C-CHEWS scores fell in an acceptable range of 0.956 (95% CI, 0.869–0.992), suggesting an optimal accuracy for identifying early warning signs of cardiopulmonary arrest. Whereas, IDO2 showed no discriminatory power to detect the adverse events with an AUC of 0.522 (95% CI, 0.389–0.652).

CONCLUSIONS:
The C-CHEWS tool provides a standardized assessment and approach to deteriorating congenital cardiac surgery patients in recognizing early postoperative deterioration.
Detection rates of adenomas, advanced adenomas, and colorectal cancers among the opportunistic colonoscopy screening population: a single-center, retrospective study
Authors: Gong Yan , Zheng Yansong , Wu Rilige , Liu Miao , Li Hong , Zeng Qiang 
Published: January 2023

Abstract

Background:
Colorectal cancer (CRC) screening is effective in reducing CRC incidence and mortality. The aim of this study was to retrospectively determine and compare the detection rate of adenomas, advanced adenomas (AAs) and CRCs, and the number needed to screen (NNS) of individuals in an average-risk Chinese population of different ages and genders.

Methods:
This was a retrospective study performed at the Institute of Health Management, Chinese People's Liberation Army General Hospital. Colonoscopy results were analyzed for 53,152 individuals finally enrolled from January 2013 to December 2019. The detection rate of adenomas, AAs, or CRCs was computed and the characteristics between men and women were compared using chi-squared test.

Results:
The average age was 48.8 years (standard deviation [SD], 8.5 years) for men and 50.0 years (SD, 9.0 years) for women, and the gender rate was 66.27% (35,226) vs. 33.73% (17,926). The detection rates of adenomas, AAs, serrated adenomas, and CRCs were 14.58% (7750), 3.09% (1641), 1.23% (653), and 0.59% (313), respectively. Men were statistically significantly associated with higher detection rates than women in adenomas (17.20% [6058/35,226], 95% confidence interval [CI] 16.74–17.53% vs. 9.44% [1692/17,926], 95% CI 8.94–9.79%, P < 0.001), AAs (3.72% [1309], 95% CI 3.47–3.87% vs. 1.85% [332], 95% CI 1.61–2.00%, P < 0.001), and serrated adenomas (1.56% [548], 95% CI 1.43–1.69% vs. 0.59% [105], 95% CI 0.47–0.70%, P < 0.001). The detection rate of AAs in individuals aged 45 to 49 years was 3.17% (270/8510, 95% CI 2.80–3.55%) in men and 1.69% (69/4091, 95% CI 1.12–1.86%) in women, and their NNS was 31.55 (95% CI 28.17–35.71) in men and 67.11 (95% CI 53.76–89.29) in women. The NNS for AAs in men aged 45 to 49 years was close to that in women aged 65 to 69 years (29.07 [95% CI 21.05–46.73]).

Conclusions:
The detection rates of adenomas, AAs, and serrated adenomas are high in the asymptomatic population undergoing a physical examination and are associated with gender and age. Our findings will provide important references for effective population-based CRC screening strategies in the future.
Recurrent Extreme Bilateral Gigantomastia Caused by Pseudoangiomatous Stromal Hyperplasia (PASH) Syndrome: A Case Report
Authors: Parisi Paola , Vinci Federica , Di Meglio Filippo , Marruzzo Giovanni , De Luca Alessandro , Ascione Andrea , Vittori Luigi , Ribuffo Diego 
Published: January 2023

Summary:
Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare and benign medical condition in which the breast tissue is affected by an abnormal myofibroblastic proliferation, which mimics a low-grade sarcoma angiomatous proliferation. PASH usually presents itself either as a palpable mass or as an incidental diagnosis during breast specimens’ histological examination. A few cases have been reported in the literature of a diffuse form of breast PASH syndrome in which the clinical presentation is a bilateral form of gigantomastia without palpable masses. In such cases, the optimal surgical management is still debated due to a significant risk of relapse after breast reduction. Mastectomy seems to be the endpoint of this condition in relapsing cases. Recent studies report a good outcome with a Tamoxifen regimen when surgery cannot be performed, supporting a hormonal component for the etiology of the condition. This study reports on an extremely rare case of bilateral, rapid, and severe PASH in a young patient, presenting as a truly disabling gigantomastia that forced the patient to use a wheelchair due to the excessive breast weights (25 kg the right breast and 21 kg the left). We describe her complicated medical history, her diagnosis, and our course of treatment.
Comparable outcomes between immune-tolerant and active phases in noncirrhotic chronic hepatitis B: a meta-analysis
Authors: Lee Han Ah , Kim Seung Up , Seo Yeon Seok , Ahn Sang Hoon , Rim Chai Hong 
Published: January 2023

Background:
Antiviral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant (IT) phase. We compared the outcomes between the untreated IT phase and the treated immune-active (IA) phase in noncirrhotic HBeAg-positive CHB patients.

Methods:
We systematically searched 4 databases, including PubMed, Medline, Embase, and Cochrane, until August 2021. The pooled incidence rates of HCC and mortality in the IT and IA cohorts and phase change in the IT cohort were investigated. Studies that included patients with liver cirrhosis were excluded.

Results:
Thirteen studies involving 11,903 patients were included. The overall median of the median follow-up period was 62.4 months. The pooled 5-year and 10-year incidence rates of HCC were statistically similar between the IT and IA cohorts (1.1%, 95% CI: 0.4%–2.8% vs. 1.1%, 95% CI: 0.5%–2.3%, and 2.7%, 95% CI: 1.0%–7.3% vs. 3.6%, 95% CI: 2.4%–5.5%, respectively, all p>0.05). The pooled 5-year odds ratio of HCC between IT and IA cohorts was 1.05 (95% CI: 0.32–3.45; p=0.941). The pooled 5-year incidence rate of mortality was statistically similar between the IT and IA cohorts (1.9%, 95% CI: 1.1%–3.4% vs. 1.0%, 95% CI: 0.3%–2.9%, p=0.285). Finally, the pooled 5-year incidence rate of phase change in the IT cohort was 36.1% (95% CI: 29.5%–43.2%).

Conclusion:
The pooled incidence rates of HCC and mortality were comparable between the untreated IT and the treated IA phases in noncirrhotic HBeAg-positive CHB patients.
Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials
Authors: Kraglund Frederik , Christensen Diana H. , Eiset Andreas H. , Villadsen Gerda E. , West Joe , Jepsen Peter 
Published: January 2023

Background and Aims:
Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis).

Approach and Results:
We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000–2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45–0.91). The RR of death without HCC was 0.69 (95% CI: 0.65–0.77). For aspirin, the RR was 1.05 (95% CI: 0.60–1.42) for HCC and 1.02 (95% CI: 0.95–1.09) for death without HCC.

Conclusions:
In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC.