bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic heterogeneity hotspots in human liver disease progression
Authors: Hlady Ryan A. , Zhao Xia , El Khoury Louis Y. , Wagner Ryan T. , Luna Aesis , Pham Kien , Pyrosopoulos Nikolaos T. , Jain Dhanpat , Wang Liguo , Liu Chen , Robertson Keith D. 
Published: July 2024

Background and Aims:
Disruption of the epigenome is a hallmark of human disease, including liver cirrhosis and HCC. While genetic heterogeneity is an established effector of pathologic phenotypes, epigenetic heterogeneity is less well understood. Environmental exposures alter the liver-specific DNA methylation landscape and influence the onset of liver cancer. Given that currently available treatments are unable to target frequently mutated genes in HCC, there is an unmet need for novel therapeutics to prevent or reverse liver damage leading to hepatic tumorigenesis, which the epigenome may provide.

Approach and Results:
We performed genome-wide profiling of DNA methylation, copy number, and gene expression from multiple liver regions from 31 patients with liver disease to examine their crosstalk and define the individual and combinatorial contributions of these processes to liver disease progression. We identified epigenetic heterogeneity hotspots that are conserved across patients. Elevated epigenetic heterogeneity is associated with increased gene expression heterogeneity. Cirrhotic regions comprise 2 distinct cohorts—one exclusively epigenetic, and the other where epigenetic and copy number variations collaborate. Epigenetic heterogeneity hotspots are enriched for genes central to liver function (eg, HNF1A) and known tumor suppressors (eg, RASSF1A). These hotspots encompass genes including ACSL1, ACSL5, MAT1A, and ELFN1, which have phenotypic effects in functional screens, supporting their relevance to hepatocarcinogenesis. Moreover, epigenetic heterogeneity hotspots are linked to clinical measures of outcome.

Conclusions:
Substantial epigenetic heterogeneity arises early in liver disease development, targeting key pathways in the progression and initiation of both cirrhosis and HCC. Integration of epigenetic and transcriptional heterogeneity unveils putative epigenetic regulators of hepatocarcinogenesis.
Discriminant prediction equation using an optical biometer for identifying postmyopic laser vision correction eyes
Authors: Nishida Tomoya , Kojima Takashi , Isogai Naoki , Yoshida Yoko , Nakamura Tomoaki 
Published: July 2024

Purpose:
To create an equation for identifying postmyopic laser vision correction (M-LVC) eyes by using corneal shape parameters in a swept-source optical coherence tomography (SS-OCT) biometer and verify its accuracy.

Setting:
Nagoya Eye Clinic, Nagoya, Japan.

Design:
Retrospective evaluation of a screening approach.

Methods:
Control participants were selected retrospectively from patients who visited the clinic for cataract surgery or refractive surgery. M-LVC patients were selected retrospectively from patients who visited the clinic for cataract surgery or M-LVC postoperative checkups. The control and post–M-LVC patients with keratometric values between 39 diopters (D) and 43 D were included in the final analysis. Patients were randomly assigned to equation-creation and validation groups in a 2:1 ratio. To discriminate post–M-LVC patients from control participants, multiple logistic regression analysis was performed with the corneal shape parameters from the optical biometer as independent variables.

Results:
The M-LVC and control groups consisted of 90 eyes from 90 patients and 97 eyes from 97 patients, respectively. The average keratometry (Ave-K) values did not differ significantly between the control and M-LVC groups (P = .187). The multiple logistic analysis identified the asymmetry component (regression coefficient, 5.357; odds ratio, 212.158) and corneal eccentricity index (regression coefficient, −5.088; odds ratio, 0.006) as explanatory variables. The area under the receiver operating characteristic curve in the predictive equation-creation group was 0.946. The sensitivity and specificity in the validation group were 93.3% and 87.5%, respectively.

Conclusions:
The M-LVC discriminant prediction equation with the topography-equipped SS-OCT biometer was effective in detecting post–M-LVC eyes with high accuracy.
Topical nonsteroidal anti-inflammatory drugs for management of pain after PRK: systematic review and network meta-analysis
Authors: Ben Ephraim Noyman Dror , Sommer Adir C. , Naaman Efrat , Gonzalez-Lugo Javier H. , Mimouni Michael 
Published: July 2024

Topic:
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) for management of pain in patients after photorefractive keratectomy (PRK).

Clinical Relevance:
Pain after PRK is a major concern for both patients and surgeons. Although evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDs.

Methods:
This study was prospectively registered with PROSPERO (ID: CRD42023417651). A systematic search of electronic databases was performed, for randomized controlled trials reporting topical NSAIDs' outcomes of corneal re-epithelization, rescue analgesics intake, and pain in days 0 to 3 after PRK (postoperative days [PODs] 0 to 3). Studies were graded for risk of bias. Data were extracted, and standardized mean differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which a frequentist approach model was fitted. Transitivity was assessed using the net split method. Treatment effectiveness was ranked using forest plots based on comparison with placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons.

Results:
Of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0, ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD −1.19, 95% CI −1.86 to −0.52), POD2 (P 0.882, SMD −1.05, 95% CI −1.82 to −0.27), and POD3 (P 0.939, SMD −1.14, 95% CI −2.1 to −0.18). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD −0.8, 95% CI −1.33 to −0.27), ketorolac, and diclofenac. Compared with placebo, re-epithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD −0.7, 95% CI −1.38 to −0.03).

Conclusions:
Flurbiprofen was favorable in pain scores on typically painful postoperative days and re-epithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAID effect sizes should be taken into consideration.
Patient‑reported outcome measures for assessing health‑related quality of life in patients with differentiated thyroid cancer: a systematic review
Authors: Xiong Lujing , Liu Lei , Xiang Yuqing , Li Chao , Dai Wei , Hu Jinchuan , Shui Chunyan , Zhou Yuqiu , Wang Xu , Cai Yongcong 
Published: July 2024

Background:
Patient-reported outcome measures (PROMs) have become important tools for evaluating health-related quality of life (HRQOL) in patients with differentiated thyroid cancer (DTC). While there are many PROMs available to measure HRQOL, there is a lack of a comprehensive overview of these PROMs. Therefore, the authors aimed to systematically review and categorize all PROMs that have been used to measure HRQOL in patients with DTC.

Materials and methods:
After determining the search strategy and identifying inclusion and exclusion criteria, articles were searched in PubMed and EMBASE from January 1900 to September 2023. Information on PROMs from the included studies, such as development language, target population, (sub)scales name, number of items per (sub)scale, completion time, and validation, was extracted and synthesized. The frequency with which PROMs were utilized in the included studies was also graphed. After innovatively classifying PROMs as five categories, all of the included PROMs were allocated to their respective categories.

Results:
A total of 330 articles fulfilled all of the criteria, and they utilized 96 different PROMs to measure HRQOL in DTC patients. The 96 PROMs were classified into five categories, namely universal PROMs (16/96), DTC-related PROMs (11/96), radioiodine-related PROMs (4/96), operation-related PROMs (37/96), and psychology-related PROMs (28/96). Among them, some PROMs were the frequently employed PROMs to assess diverse aspects of HRQOL in patients with DTC.

Conclusion:
A large number of PROMs are available for patients with DTC, which evaluate all aspects of HRQOL. Combining the relevant information and frequency of PROMs utilization, it can provide convenience and reference for researchers to select PROMs across different categories. However, a more detailed critical appraisal of the PROMs used in various clinical scenarios is required. Additionally, PROMs usage frequency in previous studies can indirectly indicate the comprehensiveness or gaps in HRQOL aspects studied, guiding further review or research.
Implementation of Full Practice Authority for Nurse Practitioners in Massachusetts
Authors: Zwilling Jana , O'Reilly-Jacob Monica 
Published: July 2024

OBJECTIVE
The aim of this study was to examine the relationship between nurse practitioner (NP) organizational climate and the implementation of full practice authority (FPA) for NPs.

BACKGROUND
In 2021, Massachusetts passed FPA for NPs. Most NPs did not experience changes to their practice. It is unknown whether NP organizational climate impacts implementation of FPA.

METHODS
A Web-based survey was distributed to NPs in Massachusetts.

RESULTS
Response rate was 50.3% (N = 147). Practice remained unchanged for most. Organizations with more favorable climates experienced more rapid implementation of FPA, resulting in improved efficiency (P = 0.049) and timeliness (P = 0.007) of care. Nurse practitioners outside hospital systems were more likely to report favorable organizational climates and positive change to their practice after FPA.

CONCLUSIONS
Organizations that facilitate implementation of FPA are likely to experience improvement in efficiency and timeliness of patient care. Nursing leadership, especially within hospital-based organizations, can help achieve these benefits by improving the organizational climate for NPs.
Mastectomy Incision Choice in Ptotic Patients Undergoing Immediate Implant-Based Reconstruction
Authors: Chemakin Katherine , Ricci Joseph A. , Benacquista Teresa , Draper Lawrence , Weichman Katie 
Published: July 2024

Abstract
Breast ptosis presents challenges for implant-based reconstruction due to the large skin envelope. Skin-reducing mastectomy reduces the envelope but must consider many other factors including complications. Limited data exist on incision impact on outcomes. We compare oblique-elliptical and Wise-pattern incisions on complications and patient-reported quality of life in immediate implant-based reconstruction.
A retrospective review of patients who underwent immediate implant-based skin-reducing mastectomy at a single institution from 2015 to 2021 was done and was divided into two cohorts: wise and oblique incisions. Demographics, complications, and patient-reported outcomes (BREAST-Q) were compared. Descriptive, t test, and chi-square test analyses, followed by adjusted linear and logistic regression models, were performed to compare complication rates and BREAST-Q scores.
Eighty-nine patient breasts were analyzed, 39 (43.8%) in the oblique (OI) and 50 (56.2%) in the wise (WI) cohort. No differences in demographics or preoperative comorbidities between groups were found. The oblique incision patients had significantly more mean total complications (OI 1.46 vs WI 0.88; P = 0.048), as well as increased incidence of explantation (OI 15 vs WI 3; P = 0.003) and cellulitis (OI 14 vs WI 3; P = 0.020) compared to wise group. Linear regression analysis revealed that incision choice was a significant predictor of complication rate (β = −1.06, 95% CI [−1.63–−0.50], P = <0.001). Logistic regression analysis showed that incision was a significant predictor of specific complications such as explantation (odds ratio = 0.10, 95% CI [0.02–0.52], P = 0.006) and cellulitis (odds ratio = 0.16, 95% CI [0.03–0.73], P = 0.018), with decreased risk of choosing wise incision. There was no difference in BREAST-Q results.
Ptotic patients with oblique incision are associated with higher rates of postoperative complications compared to wise incisions.
These findings suggest that incision choice is an important factor in postoperative complication development and emphasizes the need for further investigation and discussion with patients during preoperative planning.
Surgical Management of Iatrogenic Mercury Poisoning From Subcutaneous Injection Into the Arm
Authors: Bowen Evan C. , Benedict Katherine C. , Sullivan John M. , Baker Katherine E. , Schock Morgan E. , Walker Marc E. 
Published: July 2024

Background
Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention.

Methods
In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed.

Conclusions
Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.
Safety Profile Comparison of 2 Smooth Tissue Expander Types
Authors: Almeida Mariana N. , Alper David P. , Williams Mica C.G. , Shah Rema , Ihnat Jacqueline M.H. , Hu Kevin , Parikh Neil , Alperovich Michael 
Published: July 2024

Introduction
With the recent transition to smooth tissue expanders (TEs), functional differences between TE subtypes have not been fully elucidated. This study evaluated the differences in TE characteristics and complications between 2 commonly used Mentor smooth TE models, Artoura and CPX4.

Methods
A retrospective review of patients who received either smooth Mentor Artoura or CPX4 TE from 2012 to 2022 was conducted. Demographic data, perioperative information, pain scores, TE variables, cancer characteristics, and complications were collected. A multivariate analysis was used to evaluate the relationship between TE subtype and complications while controlling for demographic, TE characteristics, radiation, and chemotherapy exposure.

Results
During the study period, 62 smooth Artoura TEs and 79 smooth CPX4 TEs were used. Patients who received CPX4 smooth implants tended to be older (51.09 vs 46.18 years old, P = 0.02) and have a higher body mass index (28.66 vs 23.50 kg/m2, P < 0.001). There were no differences among patient comorbidities. CPX4 required on average a greater total fill volume (422.23 vs 348.07 mL, P = 0.01) and had a greater drain duration (16.91 vs 14.33 days, P = 0.05). There were no differences in TE plane placement between Artoura and CPX4. Additionally, there were no differences in complication rates, including infection, hematomas, seromas, wound breakdown, TE replacement, and capsular contracture. When controlling for body mass index, diabetes, TE plane placement, acellular dermal matrix use, radiation exposure, and chemotherapy, there was no association between TE subtype and any individual complication.

Discussion
Differences in total fill volume and drain duration were significantly different between Mentor Artoura and CPX4 implants, which may influence TE subtype selection. However, Artoura and CPX4 have excellent and equivalent safety profiles with similar complication rates, even when controlling for demographic and TE characteristics.
Limb Salvage Using Microsurgical Free Tissue Transfer in Severe Frostbite
Authors: Karir Aneesh , Donaldson Elsa Kaley , Holzer Elad , Quaife Tanis , Winter Jessica , Sigurdson Leif 
Published: July 2024

Purpose
Frostbite is often managed conservatively; however, in severe cases, microsurgical free tissue transfer is required for soft tissue coverage and limb salvage. Given its rarity, the techniques and outcomes of these cases are not well described. The purpose of this report is to present the largest case series, to date, of frostbite injuries requiring microsurgical reconstruction for limb salvage.

Methods
A single-center retrospective review was conducted of all patients who underwent free tissue transfer by a single surgeon from 2008 to 2022. Patients of all ages were included if they suffered a frostbite injury requiring free tissue transfer. Demographics, operative details, and surgical outcomes were recorded.

Results
Eight patients with frostbite injuries were included in the report. Patients had frostbite injuries either to the lower extremities (n = 4) or to both upper and lower extremities (n = 4). Sixteen free flaps were done in total including four paired chimeric and eight single free flaps. Flap recipient sites included knees (n = 5), foot/ankle (n = 3), dorsal hands (n = 2), and thumbs (n = 2). All 16 flaps survived. Five patients had complications: four with major complications requiring operative management and two with minor complications requiring conservative management. Mean follow-up time was 505.7 days (range 115–1564). All lower extremity reconstructions were able to weight-bear at an average of 125.2 days post-injury (range 87–164).

Conclusions
This case series demonstrates that free tissue transfer is a robust option for soft tissue coverage and functional limb salvage in patients with severe frostbite injuries to both upper and lower extremities.
Analysis of Relevant Predictive Indicators for Postoperative Condition Change in Brain Tumor Patients
Authors: Wang Wei , Huang Qinghua , Xu Xin , Wang Kaikai 
Published: July 2024

Background:
Novice nurse need more guidance and professional confidence. This study aimed to explore early relevant predictive indicators for postoperative condition changes in brain tumor patients, which can be used to map patients’ condition changes for novice nurses.

Methods:
The authors prospectively collected clinical data, including nursing records of cerebral tumor patients after operation from July 2020 to June 2021 in the Department of Neurosurgery. Univariant analysis and multivariable logistic regression analysis were performed to identify independent predictors, the satisfaction questionnaire for teaching nurses is used to evaluate the new nurse’s performance during perioperative period, psychometric scale is used to assess nurses’ psychological stress.

Results:
Nine hundred ninety-five cerebral tumor patients were enrolled in this study, and 115 (11.6%) patients’ conditions were changed. Relevant predictive indicators, including vision, myodynamia, urine volume, nausea, vomit, pain, Glasgow Coma Scale (GCS), and Modified Early Warning System (MEWS), among them GCS, MEWS, and vision can basically cover the above indicators through simulation and calculation of the integrated model was set as Z=22*vision+1*GCS+3*MEWS. The satisfaction rate of teaching nurses has increased from 78.125 to 86.25%. Novice nurses' psychological stress was dropped from 30.637% to 19.844%.

Conclusions:
GCS and MEWS. GCS, MEWS and vision can map patients’ condition change after cerebral tumor operation. The warning model has reduced their psychological stress, and the teaching nurse expressed that the effective evaluation of postoperative patient conditions by novice nurses reduces their nursing and teaching work greatly.
Experimental evolution of gene essentiality in bacteria
Authors: Bao Liang , Zhu Zan , Ismail Ahmed , Zhu Bin , Anandan Vysakh , Whiteley Marvin , Kitten Todd , Xu Ping 
Published: July 2024

AbstractEssential gene products carry out fundamental cellular activities in interaction with other components. However, the lack of essential gene mutants and appropriate methodologies to link essential gene functions with their partners poses significant challenges. Here, we have generated deletion mutants in 32 genes previously identified as essential, with 23 mutants showing extremely slow growth in the SK36 strain ofStreptococcus sanguinis. The 23 genes corresponding to these mutants encode components of diverse pathways, are widely conserved among bacteria, and are essential in many other bacterial species. Whole-genome sequencing of 243 independently evolved populations of these mutants has identified >1000 spontaneous suppressor mutations in experimental evolution. Many of these mutations define new gene and pathway relationships, such as F1Fo-ATPase/V1Vo-ATPase/TrkA1-H1 that were demonstrated across multipleStreptococcusspecies. Patterns of spontaneous mutations occurring in essential gene mutants differed from those found in wildtype. While gene duplications occurred rarely and appeared most often at later stages of evolution, substitutions, deletions, and insertions were prevalent in evolved populations. These essential gene deletion mutants and spontaneous mutations fixed in the mutant populations during evolution establish a foundation for understanding gene essentiality and the interaction of essential genes in networks.