bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Transcriptomic Classifier Model Identifies High-Risk Endotypes in a Prospective Study of Sepsis in Uganda*
Authors: Cummings Matthew J. , Bakamutumaho Barnabas , Tomoiaga Alin S. , Owor Nicholas , Jain Komal , Price Adam , Kayiwa John , Namulondo Joyce , Byaruhanga Timothy , Muwanga Moses , Nsereko Christopher , Nayiga Irene , Kyebambe Stephen , Sameroff Stephen , Che Xiaoyu , Lutwama Julius J. , Lipkin W. Ian , O’Donnell Max R. 
Published: August 2023

OBJECTIVES:
In high-income countries (HICs), sepsis endotypes defined by distinct pathobiological mechanisms, mortality risks, and responses to corticosteroid treatment have been identified using blood transcriptomics. The generalizability of these endotypes to low-income and middle-income countries (LMICs), where the global sepsis burden is concentrated, is unknown. We sought to determine the prevalence, prognostic relevance, and immunopathological features of HIC-derived transcriptomic sepsis endotypes in sub-Saharan Africa.

DESIGN:
Prospective cohort study.

SETTING:
Public referral hospital in Uganda.

PATIENTS:
Adults (n = 128) hospitalized with suspected sepsis.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Using whole-blood RNA sequencing data, we applied 19-gene and 7-gene classifiers derived and validated in HICs (SepstratifieR) to assign patients to one of three sepsis response signatures (SRS). The 19-gene classifier assigned 30 (23.4%), 92 (71.9%), and 6 (4.7%) patients to SRS-1, SRS-2, and SRS-3, respectively, the latter of which is designed to capture individuals transcriptionally closest to health. SRS-1 was defined biologically by proinflammatory innate immune activation and suppressed natural killer-cell, T-cell, and B-cell immunity, whereas SRS-2 was characterized by dampened innate immune activation, preserved lymphocyte immunity, and suppressed transcriptional responses to corticosteroids. Patients assigned to SRS-1 were predominantly (80.0% [24/30]) persons living with HIV with advanced immunosuppression and frequent tuberculosis. Mortality at 30-days differed significantly by endotype and was highest (48.1%) in SRS-1. Agreement between 19-gene and 7-gene SRS assignments was poor (Cohen’s kappa 0.11). Patient stratification was suboptimal using the 7-gene classifier with 15.1% (8/53) of individuals assigned to SRS-3 deceased at 30-days.

CONCLUSIONS:
Sepsis endotypes derived in HICs share biological and clinical features with those identified in sub-Saharan Africa, with major differences in host–pathogen profiles. Our findings highlight the importance of context-specific sepsis endotyping, the generalizability of conserved biological signatures of critical illness across disparate settings, and opportunities to develop more pathobiologically informed sepsis treatment strategies in LMICs.
Effect of arteriosclerotic intracranial arterial vessel wall enhancement on downstream collateral flow
Authors: Yan Liqun , Wang Zhenchang , Wang Guoshi , Li Zhenzhong , Yan Jin , Hou Yaping , Huang Boyuan , Dong Qianbo , Mu Xiaodan , Cao Wei , Zhao Pengfei 
Published: August 2023

Abstract

Background:
The effect of arteriosclerotic intracranial arterial vessel wall enhancement (IAVWE) on downstream collateral flow found in vessel wall imaging (VWI) is not clear. Regardless of the mechanism underlying IAVWE on VWI, damage to the patient's nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow. The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow.

Methods:
The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery (MCA) M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset. The patients were divided into 4 groups according to IAVWE and the stenosis ratio (Group 1, n = 17; Group 2, n = 19; Group 3, n = 13; Group 4, n = 14), and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling (3D-pCASL) and RAPID software. The National Institutes of Health Stroke Scale (NIHSS) scores of the patients were also recorded. Two-factor multivariate analysis of variance using Pillai's trace was used as the main statistical method.

Results:
No statistically significant difference was found in baseline demographic characteristics among the groups. IAVWE, but not the stenosis ratio, had a statistically significant significance on the late-arriving retrograde flow proportion (LARFP), hypoperfusion intensity ratio (HIR), and NIHSS scores (F = 20.941, P <0.001, Pillai's trace statistic = 0.567). The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables: LARFP (R
2 = 0.088, F = 10.899, P = 0.002), HIR (R
2 = 0.234, F = 29.354, P <0.001), and NIHSS (R
2 = 114.339, F = 33.338, P <0.001).

Conclusions:
Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits. It was an independent factor affecting downstream collateral flow and NIHSS scores, which should be a focus of future studies.

Trial Registration:
ChiCTR.org.cn, ChiCTR2100053661
Influence of Regional Nerve Block in Addition to General Anesthesia on Postoperative Delirium, Pain, and In-hospital Stay in Patients Undergoing Cardiothoracic Surgery: A Meta-analysis
Authors: Li Li , Liu Min , Li Songsong , Xu Jiahui , Zheng Jun , Lv Chengwei , Wu Linlin , Heng Lei 
Published: August 2023

Abstract:
This study aims to investigate whether venous injection of sedative agent or regional nerve block in alliance with major anesthesia could decrease the risk of postoperative delirium occurrence in patients receiving cardiothoracic surgery. Electronic academic databases were retrieved for related publications, and statistical software was used for data pooling and analysis. Forest plot was used to show the pooled sensitivity, specificity, and diagnostic odds ratio. Combined receiver operating characteristic curve was used to show the area under the curve of complex data. Seven studies were included for analysis. The risk of occurrence of delirium still showed no difference (risk rate = 0.93, 95% CI, 0.85–1.03) between the intervention group and placebo group. Postoperative pain feeling was more alleviated in patients with prophylactic application of regional nerve block. In addition, prophylactic application of regional nerve block could decrease the risk of postoperative in-hospital stay (risk rate = 0.28, 95% CI, 0.02–0.54). Our study demonstrated that, in elderly patients or pediatric patients undergoing cardiac surgery, prophylactic application of regional nerve block failed to decrease the incidence of postoperative delirium. However, the option of regional nerve block could decrease the duration of in-hospitalization stay and alleviate the acute pain during the postoperative period after open-heart surgery.
Minimal Scar Autologous Breast Reconstruction with Skin-sparing Mastectomy
Authors: Matsumine Hajime , Niimi Yosuke , Jibiki Norie , Sakurai Hiroyuki 
Published: August 2023

Background:
A skin paddle severely impairs the appearance of the reconstructed breast. We have established a new technique called “minimal scar autologous breast reconstruction” involving delayed nipple reconstruction using a local flap designed on the skin paddle and simultaneous resection of the residual skin paddle.

Methods:
We analyzed 20 patients with unilateral breast cancer who underwent skin-sparing mastectomy followed by immediate breast reconstruction using a free flap (deep inferior epigastric perforator flap in 13 patients and profunda artery perforator flap in seven). Approximately 1 year after primary reconstruction, nipple reconstruction using an arrow flap designed on the skin paddle and resection of the residual skin paddle were performed. Several months later, medical areola tattooing was performed. Bilateral breast symmetry scores, obtained from the distances between anatomic landmarks, were compared before and after breast reconstruction.

Results:
Postoperative complications such as necrosis of the reconstructed nipple were not observed after two-stage reconstruction, and all procedures including total resection of the skin paddle, nipple reconstruction, and medical tattooing were performed successfully in all cases. Aesthetic outcomes were excellent: comparison of symmetry scores showed no significant differences in any parameters between before surgery and after reconstruction of the nipple-areola complex.

Conclusions:
We have established step-by-step strategies for mastectomy, autologous breast reconstruction, and then nipple reconstruction, keeping in mind that the skin paddle would later be totally resected in nipple reconstruction, and thereby achieved breast reconstruction with markedly reduced postoperative scarring compared with conventional autologous breast reconstruction.
METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2–dependent mechanism
Authors: Hou Xiaoxue , Li Yuwen , Song Jiali , Peng Linya , Zhang Wen , Liu Rui , Yuan Hui , Feng Tiantong , Li Jieying , Li Wenting , Zhu Chuanlong 
Published: August 2023

Background:
N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotic cells, is dynamically regulated in response to a wide range of physiological and pathological states. Nonetheless, the involvement of METTL14-induced m6A in liver fibrosis (LF) has yet to be established.

Methods:
In vitro, HSC cell lines with knock-down and overexpression of METTL14 were constructed, and the effects of METTL14 gene on the phenotypic function of activated HSCs were observed. The proliferation rate was measured by CCK8 and EDU, the cell proliferation cycle was measured by flow detector, the migration rate was measured by Transwell, and the contractility of F-actin was observed after phalloidin staining. The downstream target gene NOVA2 of METTL14 was screened by combined sequencing of MeRIP-seq and RNA-seq, combined with signal analysis. Adeno-associated virus (AAV) was injected into the tail vein in vivo to knock down the expression of METTL14, so as to further observe the role of METTL14 in the progress of LF.

Results:
our research showed that the methylase METTL14 content was decreased in hepatic tissue from patients with LF, leading to a lowered degree of m6A modification. Functionally, we discovered that knocking down m6A methyltransferase METTL14 led to increased HSC activation and a substantial worsening of LF. Mechanically, as shown in a multiomics study of HSCs, depleting METTL14 levels decreased m6A deposition onNOVA2 mRNA transcripts, which prompted the activation of YTHDF2 to detect and degrade the decrease of NOVA2 mRNA

Conclusions:
METTL14 functioned as a profibrotic gene by suppressing NOVA2 activity in a mechanism dependent on m6A-YTHDF2. Moreover, knocking down METTL14 exacerbated LF, while NOVA2 prevented its development and partly reversed the damage.
Leveraging Radiopharmaceutical Programmatic Collaboration for Management of Pretherapy and On-treatment Urinary Incontinence
Authors: Kunos Charles A. , Lemieux Bryan P. , Recca Kimyli , Oates M. Elizabeth , El Khouli Riham H. 
Published: August 2023

AbstractMany parenteral radiopharmaceuticals available as anticancer therapy are filtered by the kidneys and excreted in the urine. Here, physician leaders of radiation medicine, nuclear medicine/molecular imaging, and the radiotheranostics programs as well as radiation safety officers, collaborated to develop a decision-making guideline for the administration of therapeutic radiopharmaceuticals in patients with pretherapy or day-of-treatment incontinence. We discussed challenges and opportunities in the screening of patients in urine collection strategies according to grade of urinary incontinence and in subsequent coordination of care. Lutetium-177 (177Lu)-based radiopharmaceutical therapies provided clinical examples of how our procedures were operationalized. Our key management issues of urinary incontinence were cutaneous radiation injury and redness, infection, or pain. In response, we developed clinical practice guidelines for the recognition and management of incontinence-related adverse events. Common adverse events of urinary incontinence were noted in this study. Our how-to guideline for the safe administration of therapeutic radiopharmaceuticals for patients with urinary incontinence warrants further investigation and should continue to be evaluated across all radiopharmaceutical therapy agents.
The platelet-to-lymphocyte ratio as an indirect outcome predictor in primary hypertension: a retrospective study
Authors: Pinho Rita , Ribeiro Rui , Ferrão Diana , Medeiros Rui , Lima Maria João , Almeida Jorge , Freitas-Silva Margarida 
Published: August 2023

ABSTRACT

Background:
Nondipper hypertensive patients have higher levels of platelet-to-lymphocyte ratio, a new studied inflammatory biomarker in primary hypertension. Furthermore, these patients have a higher risk of cardiovascular morbidity and mortality. This study aimed to assess the relationship between platelet-to-lymphocyte ratio and hypertensive pattern (dipper vs nondipper) and the association between the hypertensive pattern and major adverse cardiovascular events.

Methods:
A retrospective analysis was performed. One hundred fifty-three patients were included and classified as dipper or nondipper according to 24-hour ambulatory blood pressure measurements. Platelet-to-lymphocyte ratio was calculated based on complete blood count data.

Results:
The dipper group included 109 patients, and the nondipper group included 44 patients. Nondipper patients have 2.11 more risk of presenting a higher platelet-to-lymphocyte ratio than dipper individuals (odds ratio [OR] = 2.11; 95% CI, 1.220–3.664; P = .007). Nondipper patients also registered earlier cardiovascular events, such as acute myocardial infarction and stroke (P < .001).

Conclusions:
Nondipper hypertensive individuals registered higher levels of platelet-to-lymphocyte ratio and earlier cardiovascular events than dipper patients. Therefore, platelet-to-lymphocyte ratio could be used as an indirect predictor of cardiovascular risk in primary hypertension and contribute to optimize preventive strategies.
The Application of Adaptive Minimum Match k-Nearest Neighbors to Identify At-Risk Students in Health Professions Education
Authors: Kumar Anshul , DiJohnson Taylor , Edwards Roger A. , Walker Lisa 
Published: August 2023

Introduction
When learners fail to reach milestones, educators often wonder if any warning signs could have allowed them to intervene sooner. Machine learning can predict which students are at risk for failing a high-stakes certification examination. If predictions can be made well before the examination, educators can meaningfully intervene before students take the examination to reduce their chances of failing.

Methods
The authors used already-collected, first-year student assessment data from 5 cohorts in a single Master of Physician Assistant Studies program to implement an “adaptive minimum match” version of the k-nearest neighbors algorithm using changing numbers of neighbors to predict each student's future examination scores on the Physician Assistant National Certifying Exam (PANCE). Validation occurred in 2 ways by using leave-one-out cross-validation (LOOCV) and by evaluating predictions in a new cohort.

Results
“Adaptive minimum match” version of the k-nearest neighbors algorithm achieved an accuracy of 93% in LOOCV. “Adaptive minimum match” version of the k-nearest neighbors algorithm generates a predicted PANCE score for each student one year before they take the examination. Students are classified into extra support, optional extra support, or no extra support categories. Then, one year remains to provide appropriate support to each category of student.

Discussion
Predictive analytics can identify at-risk students who might need additional support or remediation before high-stakes certification examinations. Educators can use the included methods and code to generate predicted test outcomes for students. The authors recommend that educators use predictive modeling responsibly and transparently, as one of many tools used to support students. More research is needed to test alternative machine learning methods across a variety of educational programs.
Outcomes Associated with Concomitant Lower-Limb Amputation in Persons with Major Upper-Limb Amputation: Results of a National Study
Authors: Witt Oksana , Webster Joseph B. , Borgia Matthew , Resnik Linda 
Published: August 2023

ABSTRACT

Introduction
The challenges faced by persons with amputations are amplified for those with multiple limb loss, compared with single limb loss. However, there is limited research describing the functional outcomes of mixed upper and lower limb loss or the long-term psychosocial and health-related quality of life (HRQoL) outcomes among this group.

Materials and Methods
A cross-sectional, national telephone survey of 808 US veterans with major upper-limb amputation (ULA) with and without concomitant lower-limb amputation (LLA) who received care at US Veterans Affairs Medical Centers between 2010 and 2015 was conducted. T-tests and χ2 tests identified any significant differences in characteristics and outcomes of groups with and without LLA. Linear regressions examined the association between amputation laterality and outcomes.

Results
In comparison to those with no LLA, respondents with concomitant LLA were slightly younger (60.0 vs. 63.7) and had similar mean time in years from initial amputation (31.5 vs. 31.4). Transfemoral was the most common level of LLA (67.7%), and there was no significant difference in the distribution of ULA levels between the 2 groups. Phantom pain was less common among those with concomitant LLA compared with ULA only (64.4% vs. 74.5%, P < 0.05). No significant differences were found in prevalence of residual limb, neck, or back pain; measures of disability (QuickDASH); HRQoL; or need for activities of daily living help across the two groups.

Conclusions
In veterans with concomitant LLA and ULA, transfemoral amputation was the most common level of LLA. Those with concomitant LLA were less likely to report phantom limb pain. No statistically significant differences were found by group in need for ADL help, disability, or HRQoL.

Clinical Relevance
These results provide clinicians with a greater appreciation of the similarities and differences between the two groups in relation to amputation characteristics, pain, prosthesis utilization, prosthesis satisfaction, and functional outcomes.
Efficacy and Safety of Cold Snare Endoscopic Mucosal Resection (CS-EMR) for Nonampullary Duodenal Polyps
Authors: Mohamed Mouhand F.H. , Ahmed Khalid , Rajadurai Suvithan , Jaber Fouad , Hamid Osama , Abdalla Abubaker O. , Johnson Willie M. , Umar Shifa , Chandan Saurabh , Abdallah Mohamed , Bilal Mohammad 
Published: August 2023

Introduction:
There is an increasing interest in cold snare endoscopic mucosal resection (CS-EMR), and studies have shown its safety and efficacy for colonic polyps. This meta-analysis aims to assess the safety and efficacy of CS-EMR for the removal of duodenal adenomas.

Methods:
We conducted a comprehensive literature search of several databases, from inception through February 2023, for studies that addressed outcomes of CS-EMR for nonampullary duodenal adenomas. We used the random-effects model for the statistical analysis. The weighted pooled rates were used to summarize the technical success, polyp recurrence, bleeding, and perforation events. Cochran Q test and I
2 statistics adjudicated heterogeneity.

Results:
Six studies were included in the analysis. In all, 178 duodenal polyps were resected using CS-EMR. The pooled rates were 95.8% (95% CI 89.1–98.5%, I
2=21.5%) for technical success and 21.2% (95% CI 8.5–43.6%, I
2=78%) for polyp recurrence. With regards to CS-EMR safety, the pooled rates were 4.2% (95% CI 1.6–10.5%, I
2=12%) for immediate bleeding, 3.4% (95% CI 1.5–7.6%, I
2=0%) for delayed bleeding, 2.8% (95% CI 1.1–6.7%, I
2=0%) for perforation, and 2% (95% CL 0.5–7.5%, I
2=0%) for post-polypectomy syndrome. Rates were not significantly different for large adenomas. Three studies reported data on CS-EMR and conventional EMR. Compared with conventional EMR, CS-EMR had lower odds of delayed bleeding, OR 0.11 (CI 0.02–0.62, P value 0.012, I
2=0%).

Conclusion:
Our findings suggest that CS-EMR is a safe and effective strategy for the resection of nonampullary duodenal adenomas, with an acceptable recurrence rate. Data from larger randomized controlled studies are needed to validate our findings.
Phospholipid transport by ABCA1: the extracellular translocase or alternating access model?
Authors: Segrest Jere P. , Davidson W. Sean , Heinecke Jay W. 
Published: August 2023

Purpose of review
ATP-binding cassette transporter A1 (ABCA1) plays a key role in high-density lipoprotein (HDL) biogenesis and cholesterol export from artery wall cells. Recent evidence challenges the generally accepted model for lipid transport by ABCA1, termed the alternating access mechanism, which proposes that phospholipid moves from the inner leaflet to the outer leaflet of the plasma membrane.

Recent findings
In contrast to the standard model, our computer simulations of ABCA1 indicate that ABCA1 extracts phospholipid from the plasma membrane's outer leaflet. The lipid then diffuses into the interior of ABCA1 to contact a structure termed the ‘gateway’. A conformational change opens the gateway and forces the lipid through a ring-shaped domain, the ‘annulus orifice’, into the base of an elongated hydrophobic tunnel in the transporter's extracellular domain. Engineered mutations in the gateway and annulus strongly inhibited lipid export by ABCA1 without affecting cell-surface expression levels of the transporter, strongly supporting the proposed model.

Summary
Our demonstration that ABCA1 extracts lipid from the outer face of the plasma membrane and forces it into an elongated hydrophobic tunnel contrasts with the alternating access model, which flops phospholipid from the membrane's inner leaflet to its outer leaflet. These results suggest that ABCA1 is a phospholipid translocase that transports lipids by a mechanism distinct from that of other ABC transporters.