bluuebunny/crossref_metadata_2025 huggingface dataset:
A Focused Update to the Clinical Practice Guidelines for the Prevention and Management of Pain, Anxiety, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU
Authors: Lewis Kimberley , Balas Michele C. , Stollings Joanna L. , McNett Molly , Girard Timothy D. , Chanques Gerald , Kho Michelle E. , Pandharipande Pratik P. , Weinhouse Gerald L. , Brummel Nathan E. , Chlan Linda L. , Cordoza Makayla , Duby Jeremiah J. , Gélinas Céline , Hall-Melnychuk Erin L. , Krupp Anna , Louzon Patricia R. , Tate Judith A. , Young Bethany , Jennings Ron , Hines Anitra , Ross Chris , Carayannopoulos Kallirroi Laiya , Aldrich J. Matthew
Published: February 2025

Rationale:

Critically ill adults are at risk for a variety of distressing and consequential symptoms both during and after an ICU stay. Management of these symptoms can directly influence outcomes.

Objectives:

The objective was to update and expand the Society of Critical Care Medicine’s 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU.

Panel Design:

The interprofessional inclusive guidelines task force was composed of 24 individuals including nurses, physicians, pharmacists, physiotherapists, psychologists, and ICU survivors. The task force developed evidence-based recommendations using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Conflict-of-interest policies were strictly followed in all phases of the guidelines, including task force selection and voting.

Methods:

The task force focused on five main content areas as they pertain to adult ICU patients: anxiety (new topic), agitation/sedation, delirium, immobility, and sleep disruption. Using the GRADE approach, we conducted a rigorous systematic review for each population, intervention, control, and outcome question to identify the best available evidence, statistically summarized the evidence, assessed the quality of evidence, and then performed the evidence-to-decision framework to formulate recommendations.

Results:

The task force issued five statements related to the management of anxiety, agitation/sedation, delirium, immobility, and sleep disruption in adults admitted to the ICU. In adult patients admitted to the ICU, the task force issued conditional recommendations to use dexmedetomidine over propofol for sedation, provide enhanced mobilization/rehabilitation over usual mobilization/rehabilitation, and administer melatonin. The task force was unable to issue recommendations on the administration of benzodiazepines to treat anxiety, and the use of antipsychotics to treat delirium.

Conclusions:

The guidelines task force provided recommendations for pharmacologic management of agitation/sedation and sleep, and nonpharmacologic management of immobility in critically ill adults. These recommendations are intended for consideration along with the patient’s clinical status.
Wearable Devices for Hemodynamic Assessment in Cardiovascular Disease: A Short Literature Review
Authors: Singh Jyotpal , Ellingson Chase J. , Gagarinova Maria , Thakkar Rishi , Mehta Neha , Ahmad Kirrat , Sultana Sabiha , Bhat Shivani , Dehghani Payam
Published: February 2025

Hemodynamic parameters are frequently used in patients with cardiovascular disease to assess cardiac function, monitor disease progression, propose interventions, and determine prognosis. However, they require extensive resources, including specialized equipment and trained personnel, to measure with accuracy and precision. Wearable devices such as wristwatches have been shown to assess heart function, such as heart rate and detection of irregular heart rhythms. These wearable devices have also evolved to measure hemodynamic variables in a noninvasive, dynamic, and rapid manner. However, there is limited research on the accuracy of these wearables for hemodynamic function. This review assesses wearable devices and their utility compared with a clinical reference standard for hemodynamic assessment and highlights the strengths and weaknesses of such devices. Limited studies have found that wearable devices can demonstrate strong correlations when assessing cardiac output, stroke volume, systolic blood pressure and timing intervals, and pre-ejection period. Reproducibility studies in similar clinical conditions are needed, and many of the wearable devices have not received FDA/Health Canada approval, restricting their clinical use. Our review summarizes the current research landscape of wearable devices and hemodynamic assessment and proposes a framework for future research applications.
A Rare Cutaneous Presentation of Malignant Tenosynovial Giant Cell Tumor
Authors: Luyten Sophia , Mehta Apoorva , Gru Alejandro A.
Published: February 2025

Malignant tenosynovial giant cell tumor (MTGCT) is a rare and aggressive variant of tenosynovial giant cell tumors, with fewer than 60 reported cases. Although typically localized to joints and soft tissues, cutaneous presentations of MTGCT are exceedingly rare, with only a handful of documented cases involving direct dermal invasion. Here we report the case of an 88-year-old man with a history of nonmelanoma skin cancers who presented with a friable, ulcerated 2.5 cm nodule on the midchest. The lesion, present for approximately 1 month, was excised and found to be a malignant TGCT. Histopathology revealed a neoplasm with multinucleated giant cells and malignant features such as numerous and atypical mitotic figures, necrosis, and severe cellular pleomorphism. Immunohistochemistry showed positivity for CD45 and CD68, with weak partial expression of smooth muscle actin, and negative for CD34, P40, SOX10, pancytokeratin, CD163, CD1a, S100, and Melan-A, confirming the diagnosis. The patient underwent complete surgical excision. This case highlights a rare presentation of MTGCT with direct cutaneous involvement, adding to the sparse literature on this malignancy. Early recognition and accurate diagnosis of such unusual presentations are crucial because of the tumor's aggressive potential.
Dermatofibrosarcoma Protuberans Arising in a Digit: A Case Report
Authors: Sun Samantha , Odom Jordan , Ruiz Nathalie , Moody Patricia
Published: February 2025

Dermatofibrosarcoma protuberans (DFSP) is a rare slow-growing soft tissue sarcoma that is usually found on the trunk or extremities. This report highlights an exceedingly rare case in which a DFSP arose on the digit of a 43-year-old man. Clinical and histologic analysis revealed an atypical CD34-positive tumor with differentials including DFSP and multiple similar entities. However, fluorescence in situ hybridization studies revealed a COL1A1 translocation to the platelet-derived growth factor B (22q13.1) locus, t(17;22)(q22;q13), confirming the diagnosis of DFSP. Although rare, this case highlights the importance of including DFSP on the differential in CD34-positive acral tumors, with cytogenetic analysis crucial for accurate diagnosis and treatment.
Coronary Perforation Occurring During Percutaneous Coronary Intervention Is Associated With Persistently High Mortality and Complications
Authors: Movahed Mohammad Reza , Satapathy Nishant , Hashemzadeh Mehrtash
Published: February 2025

Introduction:

Coronary perforation is one of the major complications of percutaneous coronary intervention (PCI). The goal of this study was to evaluate adverse outcomes and mortality in patients suffering from coronary perforation during PCI above the age of 30.

Methods:

The National Inpatient Sample database, years 2016–2020, was studied using International Classification of Diseases, Tenth Revision codes. Patients suffering from perforation were compared with patients without perforation during PCI.

Results:

PCI was performed in a weighted total of 10,059,269 patients. Coronary perforation occurred in 11,725 (0.12%) of all PCI performed. The mortality rate of patients with perforations was very high in comparison to patients without perforations. (12.9% vs. 2.5%, odds ratio, 5.6; CI, 5-6.3; P < 0.001). Furthermore, patients with coronary perforations had much higher rates of urgent coronary bypass surgery, tamponade, cardiac arrest, and major cardiovascular outcomes. Mortality remained high and over 10% in the 5-year study period.

Conclusions:

Using a large national inpatient database, all-cause inpatient mortality in patients with coronary perforation is very high (over 10%), with persistently high mortality rates over the years, suggesting that treatment of perforations needs further improvement.
Visual and subject-reported outcomes of a wavefront shaping extended depth of focus intraocular lens implanted bilaterally with monovision
Authors: Teus Miguel A. , Kohnen Thomas , Ball James , Saelens Isabelle E.Y. , Sutton Gerard , Lawless Michael , Vives Caridad Perez , Lapid-Gortzak Ruth
Published: February 2025

Purpose:

To report visual and subject-reported outcomes after bilateral implantation of non-diffractive extended-depth-of-focus (EDoF) intraocular lens (IOL) (AcrySof IQ Vivity) with monovision correction during cataract or refractive lens exchange (RLE) surgery.

Setting:

Europe, Australia, and New Zealand

Design:

Subgroup analysis of Vivity registry

Methods:

Binocular uncorrected and corrected visual acuities at distance (UCDVA/CDVA), intermediate (UCIVA/DCIVA), and near (UCNVA/DCNVA) were assessed at 3-6 months after implantation. Subject-reported outcomes (satisfaction, spectacle independence, visual disturbances) were evaluated. Data were reported by surgery type and monovision level at low (>-0.75D and ≤-0.50D), medium (>-1.00D and ≤-0.75D), and high (≤-1.00D).

Results:

Overall, 200 (of 885) subjects met the monovision criteria (cataract, n=170; RLE, n=24). Excellent binocular UCDVA and UCIVA and excellent/good UCNVA (mean±SD logMAR) were noted for cataract (0.031±0.102; 0.081±0.114; 0.217±0.144) and RLE (0.006±0.093; -0.003±0.089; 0.123±0.097) groups, respectively. Most subjects were spectacle-independent for distance and intermediate vision and very/fairly satisfied with sight; >87% from each surgery group reported no visual disturbances. Excellent UCDVA was preserved at low and medium monovision. Better UCNVA was observed for medium and high vs. low monovision levels, whereas spectacle independence for distance and intermediate was higher for medium vs. low/high monovision. High subject satisfaction and minimal visual disturbances were reported regardless of monovision level.

Conclusions:

Monovision correction with the non-diffractive EDoF IOL demonstrated excellent-to-good VA at all distances, high levels of spectacle independence and subject satisfaction, and minimal visual disturbances after cataract and RLE surgeries. Overall, medium monovision level performed most favorably, achieving good near VA while preserving excellent distance and intermediate vision.
Prostatic Adenocarcinoma Presenting as a “Giant” Abdominal Mass on PSMA PET/CT
Authors: Huang Juncheng , Loi Hoi Yin
Published: February 2025

We report a 75-year-old man who presented with an abdominal mass associated with urinary retention. Physical examination revealed an enlarged prostate. Bedside ultrasound demonstrated a very large abdominal-pelvic mass inseparable from the bladder. PSA levels were high at 2393 ng/mL. Transrectal ultrasound-guided biopsy confirmed prostatic acinar adenocarcinoma (Gleason 4+5). PSMA PET/CT scan showed a large, intensely PSMA-avid abdominal-pelvic mass involving the prostate, seminal vesicles, and bladder, with peritoneal metastasis. No osseous metastasis was noted. This case highlights how prostatic adenocarcinoma can present as a giant abdominopelvic mass, clearly illustrated on PSMA PET/CT.
Pediatric Resuscitation Skill of Bag-Tube Manual Ventilation: Developing and Using a Mobile Simulation Program to Assess Competency of a Multiprofessional PICU Team
Authors: McCormick Anna E. , Friess Stuart H. , Quayle Kimberly S. , Lin John C. , Manga Arushi
Published: February 2025

Objectives:

To assess the skill of bag-tube manual ventilation with the flow-inflating bag in multiprofessional PICU team members using a mobile simulation unit.

Design:

Prospective observational study from January 2022 to April 2022.

Setting:

In situ mobile simulation using the flow-inflating bag in an academic PICU.

Subjects:

Multiprofessional PICU team members including nurses, respiratory therapists, nurse practitioners, fellows, and attendings.

Interventions:

None.

Measurements and Main Results:

We enrolled 129 participants who twice completed 1-minute tasks performing bag-tube manual ventilation with a flow-inflating bag. Sessions were video recorded; four could not be analyzed. Only 30% of participants reported being very to extremely confident, and the majority (62%) reported infrequent skill performance. Task success was defined as achieving target pressure ranges during 80% of the delivered breaths, respiratory rate (RR) of 25–35 breaths/min, and successful pop-off valve engagement. Only five of 129 participants (4%) achieved successful ventilation as defined. Overall, participants were more likely to deliver lower pressures and faster rate. Maintaining target positive end-expiratory pressure (PEEP) was least likely to be achieved (19% success), followed by RR (52%), pop-off valve (64%), then peak inspiratory pressure (71%). Nurses were less likely to achieve target pressures compared with all other professions.

Conclusions:

Multiprofessional PICU team members have highly variable self-confidence with bag-tube manual ventilation using a flow-inflating bag. Observed performance demonstrates rare success with achieving targeted ventilation parameters, in particular maintenance of PEEP. Future research should focus on developing mobile simulation units to facilitate profession-specific, real-time coaching to teach high-quality manual ventilation that can be translated to the bedside.
Tracheal Intubation by Attending Physicians in a U.S. Registry, 2016–2020: Analysis by PICU Participation in a Skills Maintenance Program and Fellowship Training
Authors: Kishida Mizue , Berg Robert A. , Napolitano Natalie , Berkenbosch John , Talukdar Andrea , Jung Philipp , Malone Matthew P. , Parsons Simon J. , Harwayne-Gidansky Ilana , Nett Sholeen , Glater Lily , Krawiec Conrad , Shenoi Asha , Al-Subu Awni , Polikoff Lee , Kelly Serena P. , Adams Carolyn K. , Giuliano John S. , Ambati Shashikanth , Tellez David , Martin Rebecca J. , Lee Anthony , Breuer Ryan K. , Biagas Katherine V. , Mallory Palen P. , Corbett Kelly L. , Bysani G. Kris , Ducharme-Crevier Laurence , Wirkowski Samantha , Pinto Matthew , Toal Megan , Marlow Rachel K. , Adu-Darko Michelle , Shults Justine , Nadkarni Vinay , Nishisaki Akira ,   for the National Emergency Airway Registry for Children (NEAR4KIDS) and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: February 2025

Objectives:

Tracheal intubation (TI) is a critical skill for PICU attending physicians to maintain. We hypothesize that attendings perform fewer TIs and have lower success rate in PICU programs with a Pediatric Critical Care Medicine (PCCM) fellowship.

Design:

Retrospective study using the National Emergency Airway Registry for Children (NEAR4KIDS) from July 2016 to June 2020. Exposures were presence of PCCM fellowship and attending TI skill maintenance program (SMP). The primary outcome was attending’s first attempt success and the secondary outcome was adverse airway outcome in the first attempt.

Setting:

Thirty-three PICUs in North America.

Patients:

Children receiving TI.

Interventions:

None.

Measurements and Main Results:

Overall, 23 of 33 PICUs had a PCCM fellowship with three of 23 having an attending TI SMP. Attendings performed TI in 24.1% (2,728/11,323): 13.9% (13.8 TI/yr per PICU) in PICUs with a fellowship vs. 66.0% (36.6 TI/yr per PICU) without a fellowship (p < 0.001). Attending first attempt success in PICUs with vs. without fellowships was 70.5% vs. 81.3% (difference, 10.8% [95% CI, 7.6–14.0%]; p < 0.0001). After controlling for confounders, attendings in a PICU with a fellowship had lower odds for first attempt success (adjusted odds ratio [aOR], 0.65 [95% CI, 0.47–0.90]). We failed to find an association between attending first attempt success and PICU program type, with vs. without a TI SMP (74.0% vs. 69.5%; p = 0.146). The adverse airway outcome rate of the TI with attending’s first attempt was lower in PICU programs with vs. without a TI SMP (32.8% vs. 40.3%; p = 0.020). However, after adjusting for confounders, we failed to exclude the possibility of near halving of odds of adverse outcome (aOR, 0.75 [95% CI, 0.55–1.01]; p = 0.058).

Conclusions:

Attendings in PICU programs with a fellowship have fewer opportunities to perform TI and lower first attempt success rates. Opportunities exist for attending TI skill maintenance, especially in PICUs with a PCCM fellowship.
Durable Central Venous Access for Pediatric Cardiac Patients: Secondary Analysis of a Single-Center, Retrospective Cohort Study, 2015–2021
Authors: Shostak Eran , Dagan Ovadia , Tzeitlin Yelena , Goldberg Ori , Raz Gal , Amir Gabriel , Feinstein Yael , Schiller Ofer
Published: February 2025

OBJECTIVES:

There are several options for durable venous access for pediatric cardiac patients and the insertion techniques, locations, and complications potentially differ. The study aimed to evaluate our experience of upper extremity peripherally inserted central catheters (PICCs) and durable tunneled femoral central venous catheters (TF-CVCs) in young pediatric cardiac ICU (PCICU) patients.

Design:

Retrospective cohort study, 2015–2021.

Setting:

PCICU in a tertiary medical care center.

Patients:

All patients younger than 1.5 years old who underwent bedside insertion of TF-CVC or upper extremity PICC between December 2015 and December 2021.

Interventions:

None.

Measurements and Main Results:

The cohort included 226 durable lines, inserted in patients 2–550 days old, with 111 upper extremity PICCs and 115 TF-CVCs. In the two groups, receipt of PICC vs. TF-CVC placement was associated with older age (125.6 vs. 53.4 d; p = 0.005), and shorter duration of mechanical ventilation (9.0 vs. 25.5 d; p < 0.001). PICC vs. TF-CVC use was associated with a higher rate of central line-associated bloodstream infection (CLABSI) (7.14 vs. 2.38/1000 line days; p = 0.004) and more thrombosis events (5 vs. 0; p = 0.008). When adjusted for CLABSI-free line days, TF-CVCs (relative to upper limb PICCs) was associated with close to one-third of the odds of CLABSI (odds ratio [OR], 0.31 [95% CI, 0.13–0.78]); similarly, when adjusted for line days close to one-third of the odds of any complication, that is, CLABSI, dislodgment, occlusion, or thrombosis (OR, 0.31 [95% CI, 0.14–0.65]).

Conclusions:

In our 2015–2021 PCICU experience of using durable TF-CVC inserted at the bedside, vs. upper extremity PICCs, in neonates and infants, we found an associated one-third the odds of CLABSI and overall complications. A prospective study of subcutaneous tunneling in various locations of catheters on CLABSI and overall complication rates is needed.
Dieulafoy Lesion in a Pediatric Patient
Authors: Barshay Meylakh , Cowan Maiya , Beucher Meghan
Published: February 2025

Objective:

Our aim is to describe a rare etiology of an upper gastrointestinal bleeding (UGIB) to help pediatric emergency medicine clinicians improve their understanding of its presentation as well as the standard therapeutic approach to UGIB.

Methods:

This is a retrospective case report of a patient who presented to the Pediatric Emergency Department of Hasbro Children's Hospital and who was found to have a UGIB secondary to a Dieulafoy lesion.

Results:

The etiology of UGIBs varies by geography and patient age but includes esophagitis, Mallory-Weiss tears, gastritis, peptic ulcers, and foreign body ingestion. Given the overlapping presenting symptoms, history and physical are critical to identifying likely etiology and guiding treatment. This patient improved after definitive treatment with endoscopy and hemo-clips.

Conclusions:

Children with symptoms of UGIB should receive prompt resuscitation and stabilization, and clinicians should maintain an index of clinical suspicion for less common pediatric pathologies, such as malignancy or arterial bleeding.
Eosinophilic Salpingitis
Authors: AbdullGaffar Badr , Almulla Amal
Published: February 2025

Chronic salpingitis presents with various inflammatory patterns due to different causes. Eosinophil-rich salpingitis is rare and primarily associated with parasitic infestations. We aim to report our findings of eosinophil-rich salpingitis in a series of women who presented with ruptured hemorrhagic ovarian corpus luteum cysts and tubal schistosomiasis accompanied by ectopic tubal pregnancies. Eight women (age range: 31–40 yr, average age: 34 yr) met the inclusion criteria for eosinophil-rich salpingitis. The tubes showed a dense eosinophilic infiltrate throughout the tubal wall with edema and hemosiderin pigment deposition﻿. The mucosal plicae were broadened due to vascular congestion, edema, and conspicuous eosinophilic infiltrates with siderophages. Luminal hemorrhage was present. Six patients had ipsilateral ruptured hemorrhagic ovarian corpus luteum cysts with ruptured tubal ectopic pregnancies, whereas 2 patients had Schistosoma ova in the tube. The close proximity of the tubal fimbriae to the ovary suggests that the tubal cavity is a potential reservoir of the extruded contents from ruptured hemorrhagic luteal cysts. Theoretically, the engulfed contents could move down the tubal lumen, adhere to the epithelium, and elicit an allergic inflammatory reaction in the tubal mucosa and mural wall. This phenomenon may play a role in postinflammatory fibrous adhesion and ectopic pregnancies. Eosinophilic salpingitis is a rare, unilateral, localized, secondary inflammatory reaction of the fallopian tubes. Apart from parasitic infestations, an inflammatory response to ruptured hemorrhagic corpus luteum cysts should be considered as a potential association when other causes are excluded. Certain histopathologic features may provide clues to this association. Further validation is warranted to determine whether these findings are associations or mere coincidences.
Ideal Outcome after Left Pancreatectomy in North America, Germany, the Netherlands, and Sweden
Authors: Hendriks Tessa E , Augustinus Simone , Andersson Bodil , Williamson Caroline , Beane Joal D. , Davis Catherine , Ghadimi Michael , Werner Jens , Uhl Waldermar , Wellner Ulrich F. , Keck Tobias , Bonsing Bert A , Groot Koerkamp Bas , van Santvoort Hjalmar C. , Björnsson Bergthor , Besselink Marc G , Pitt Henry A , Tingstedt Bobby ,   for Global Audits on Pancreatic Surgery Group (GAPASURG)
Published: February 2025

Background:

Composite outcome measures aim to provide a more holistic view when determining the effectiveness and safety of surgical interventions. Recently, ‘Ideal Outcome’ (IO) harmonized the European and American composite outcome of pancreatic surgery. The rate of IO after pancreatoduodenectomy was 54% but is unknown after left pancreatectomy(LP).

Methods:

This transatlantic analysis included patients after LP from the audits in North America (NSQIP), Germany (StuDoQ), the Netherlands (DPCA), and Sweden (SNPPCR) (2014 – 2020). IO is obtained in the absence of (1)in-hospital mortality, (2)severe complications (Clavien-Dindo≥3), (3)postoperative pancreatic fistula (ISGPS grade B/C), (4)reoperation, (5)hospital stay exceeding the 75th-percentile, and (6)readmission. Clinical predictors of IO were identified using a multivariable logistic regression.

Results:

Overall, 20,126 patients after LP were included (37.8% minimally invasive). The rate of IO after LP was 59.1%. The rate of IO varied among the four audits: North America 58.5%, Germany 53.4%, the Netherlands 56.9%, and Sweden 61.7% (P<0.001). Among all variables, the rate of postoperative pancreatic fistula differed the most: North America 9.8%, Germany 23.9%, the Netherlands 20.5%, and Sweden 10.6% (P<0.001). Minimally invasive LP was associated with higher rates of IO (65.4% vs 53.3%, P<0.001) compared to open LP. No difference in the IO was observed between robot-assisted and laparoscopic LP.

Conclusion:

The new composite outcome measure IO was reached in 59% patients after LP and varied between four transatlantic audits. Minimally invasive LP was associated with higher rates of IO. IO can be used for evaluating, comparing, and improving patient outcomes between the four audits, especially regarding postoperative pancreatic fistula.
Diagnostic Performance of Gene Expression and dd-cfDNA in Multiorgan Transplant Recipients
Authors: Zaky Ziad S. , Clifford Stephanie A. , Fleming James N.
Published: February 2025

Background.

The aim of this analysis was to evaluate early signals of the utility of gene expression profile (GEP) and donor-derived cell-free DNA (dd-cfDNA) for ruling out subclinical rejection in multiorgan transplant recipients.

Methods.

This was a prospective, single-center, observational pilot study that began enrolling patients in September 2022. Participants were enrolled after providing informed consent and had biomarker samples drawn before surveillance or for-cause biopsy. GEP result of TX was considered negative and a dd-cfDNA of ≤0.69% was considered negative, regardless of a nonrenal organ.

Results.

There were 49 participants with 55 surveillance and/or for-cause biopsies. After exclusion of biopsies not paired with biomarkers, 51 biopsies were evaluated with at least 1 biomarker. Fifty-one biopsies had paired GEP results, whereas 47 biopsies had paired dd-cfDNA results. Overall, there were 12 biopsy-proven acute rejections (24%), 5 of which were T cell–mediated rejections (4-1A and 1-1B), 2 were antibody-mediated rejections, and 5 were borderline for T cell–mediated rejections. GEP by itself in 51 biopsies demonstrated a sensitivity of 17%, specificity of 74%, positive predictive value of 17%, negative predictive value of 74%, and balanced accuracy of 61%. Among 47 paired biopsies, dd-cfDNA demonstrated a sensitivity of 67% and specificity of 37%. Median dd-cfDNA was above the positivity threshold for both participants with rejection on biopsy and without (1.86% versus 1.35%, respectively). When evaluating GEP, specifically in surveillance biopsies and patients with liver transplants, diagnostic performance was maintained.

Conclusions.

In this pilot analysis, GEP maintained a high negative predictive value in a multiorgan cohort, regardless of the nonrenal organ. dd-cfDNA did not have good performance when using the kidney threshold cutoff, which was expected and driven by the liver component of multiorgan recipients. Further technological advances with dd-cfDNA to differentiate organs and multiple donors could be impactful. The results support the use of GEP for ruling out kidney rejection in a multiorgan population, including those with a liver transplant. Further evaluation is necessary to confirm the results.
Disrupting Viral Replication in Human Metapneumovirus: Targeting Key Proteins with Unani Phytochemicals through Structural Dynamics and Energetics
Authors: Dubey Amit
Published: February 2025

Emerging viral infections pose significant global health challenges, necessitating the exploration of novel antiviral therapeutics. This study investigates the antiviral potential of bioactive compounds derived from theUnani system of medicine, leveragingmolecular docking, molecular dynamics simulations, pharmacokinetic profiling, and quantum chemical calculationsto assess their efficacy against theHuman Metapneumovirus (HMPV) target protein (PDB ID: 5WB0).Molecular docking studies revealed thatCrocin (−9.5 kcal/mol), Quercetin (−9.3 kcal/mol), and Oleuropein (−9.0 kcal/mol)exhibited remarkable binding affinities, engaging inmultiple hydrogen bonds and hydrophobic interactions, comparable to standard antiviral drugsRemdesivir (−9.2 kcal/mol) and Favipiravir (−8.8 kcal/mol). These findings were further supported bymolecular dynamics simulations, where Crocin and Quercetin maintained exceptionalbinding stability (RMSD ~1.8 Å, MM-PBSA energy ~ −80.5 kcal/mol), reinforcing their potential asHMPV inhibitors.Additionally,pharmacophore modeling and electronic structure analysishighlighted stronghydrogen bonding capacity, dipole moment, and electrostatic potentialfor these bioactives, facilitating optimal target interactions.Pharmacokinetic and toxicological assessmentsconfirmed theirhigh bioavailability, metabolic stability, and minimal toxicity, positioning them as promising candidates for further drug development.Overall, this comprehensive computational study underscores thetherapeutic relevance of Unani-derived compounds, paving the way fornatural antiviral interventions. Futurein vitro and in vivo investigationswill be essential to validate their clinical efficacy and optimize their drug-like properties.
FlowerPatch: New Method to Measure Nectar Volume in Artificial Flowers
Authors: Lara E. , Agosto J. , Tugrul G. , Megret R. , Flórez E.
Published: February 2025

This article proposes a new Flower Patch Nectar Sensor to address the problem of detecting and measuring nectar in artificial flowers used in experiments on pollinator behavior. Traditional methods have focused mainly on recording the visits of pollinators to the flowers, without addressing the dynamic variations in nectar in terms of volume and concentration. The proposed approach provides more detailed information about the nectar consumption by bees and allows determination of the optimal time to refill the flowers. This study introduces an innovative method that uses electrodes and an oscillator circuit to measure the volume of nectar present in the flower. The system correlates the concentration of nectar with a frequency signal that can be processed by a microcontroller. It was evaluated using initial volumes ranging from 1 µL to 4 µL, demonstrating its ability to accurately detect variations in nectar, even up to the point where the frequency approaches zero. The results confirm that this method allows us to identify how the reward offered to pollinators (represented by nectar) varies over time, in terms of concentration, under both controlled and natural conditions. Additionally, graphs are presented that show the relationship between an initial volume of 4 µL and variations in the frequency signal over a period of 25 minutes, highlighting the influence of these factors on nectar dynamics. This work not only introduces an innovative approach for the dynamic monitoring of nectar in artificial flowers, but also lays the groundwork for future studies on the physical and chemical modeling of nectar in response to environmental conditions.
Analysis of aroma compounds in Barbecued Mutton (Kebab) during different storage periods and exploration of customer preferences
Authors: Alim Aygul
Published: February 2025

Kebab (barbecued mutton) is a traditional meat product with a rich roasted meaty aroma and is highly favored by consumers. However, there are no reports on the flavor changes of different roasted meat tissues during storage, and there are no studies on why consumers prefer to eat Kebab. This study employed GC-IMS to explore the changes in aroma compounds in Kebab. Simultaneously, molecular docking was used to explore the mechanism of aroma compounds that trigger pleasure and to infer the optimal storage methods. A total of 61 volatile compounds, including aldehydes, alcohols, esters, ketones, acids, furans, ethers, and terpenes, were identified. Sensory evaluation revealed that when the storage time increased, the sour and sulfur aromas of mutton were strong, whereas the fatty aroma significantly increased and decreased in fat and lean meat. Additionally, a sense of pleasure was speculated by exemplifying six key aroma compounds. The differences in aroma compounds in the Kebab samples were clearly observed and indicated that the lean meat kebab maintained numerous meaty aroma compounds during storage until the 28th day. This is the first study to reveal the potential mechanism of the pleasure generated by eating Kebab, which will provide practical application value for evaluating the flavor of Kebab.
Amniotic Fluid Reduces Liver Fibrosis By Attenuating Hepatic Stellate Cell Activation
Authors: Bowen Charles M. , Ditmars Frederick , Liu Naiyou , Abril Jose Marri , Ajasin David , Russell William K , Stevenson Heather L , Eugenin Eliseo A , Fair Jeffrey H , Fagg William S
Published: February 2025

Regardless of the source of injury or metabolic dysfunction, fibrosis is a frequent driver of liver pathology. Excessive liver fibrosis is caused by persistent activation of hepatic stellate cells (HSCs), which is defined by myofibroblast activation (MFA) and the epithelial-mesenchymal transition (EMT). Strategies to prevent or reverse this HSC phenotype will be critical for successful treatment of liver fibrosis. We have previously shown that full-term, cell-free human amniotic fluid (cfAF) inhibits MFA and EMT in fibroblasts in vitro. We hypothesize that cfAF treatment can attenuate HSC activation and limit liver fibrosis. We tested if cfAF could prevent liver fibrosis or HSC activation in murine models of liver damage, three-dimensional hepatic spheroids, and HSC cultures. Administering cfAF prevented weight loss and the extent of fibrosis in mice with chronic liver damage without stimulating deleterious immune responses. Gene expression profiling and immunostaining indicated that cfAF administration in carbon tetrachloride-treated mice reduced EMT- and MFA-related biomarker abundance and modulated transcript levels associated with liver metabolism, immune regulatory pathways, and cell signaling. cfAF treatment lowered MFA biomarker levels in a dose-dependent manner in hepatic spheroids exposed to ethanol. Treating HSCs with cfAF in vitro strongly repressed EMT. Multi-omics analyses revealed that it also attenuates TGFβ-induced MFA and inflammation-associated processes. Thus, cfAF treatment prevents liver fibrosis by safeguarding against persistent HSC activation. These findings suggest that cfAF may be a safe and effective therapy for reducing liver fibrosis and preventing the development of cirrhosis and/or hepatocellular carcinoma.
LAVR-289, a New Orally Bioavailable Inhibitor of Adenovirus Replicationin vitroandin vivo
Authors: Quentin-Froignant Charlotte , Tollefson Ann , Cline-Smith Anna , Kappler-Gratias Sandrine , Landrein Nicolas , Roy Vincent , Agrofoglio Luigi A. , Toth Karoly , Wodrich Harald , Gallardo Franck
Published: February 2025

Adenoviruses are responsible for a range of pathologies, including respiratory infections in children, accounting for 5-10% of such cases. Although most adenovirus infections are self-resolving, they can cause serious illness, particularly in immunocompromised individuals. There is currently no approved treatment for adenovirus infections, although various therapeutic approaches are under investigation, including nucleoside analog inhibitors of replication. However, these treatments have shown limited efficacy. In this study, we report on the antiviral activity of LAVR-289, a broad-spectrum acyclonucleoside phosphonate exhibiting potentin vitroefficacy against several adenovirus serotypes, comparable to that of brincidofovir. LAVR-289 specifically inhibits viral replication, blocking the formation of viral replication centers and preventing late protein expression without affecting viral entry or delivery of viral genomes to the nucleus.In vivousing immunocompromised Syrian hamsters infected with HAdV-C6, oral administration of LAVR-289 resulted in 100% animal survival. These results suggest that LAVR-289 holds promise as a potential therapy for adenovirus infections, particularly in immunocompromised patients.

Highlights

LAVR-289 is a unique acyclic nucleoside phosphonate prodrug.

LAVR-289 displays antiviral activity against Adenovirus with an EC50of about 100 nM against HAdV-C5 ANCHOR.

LAVR-289 inhibits viral replication by targeting viral DNA polymerase, preventing DBP clustering and replication center formation.

In immunosuppressed Syrian hamsters, LAVR-289 is well tolerated and ensures 100% survival while effectively stopping virus replication.

LAVR-289's broad-spectrum activity positions it as a promising treatment for immunocompromised patients facing multiple viral infections.
Investigating the obstacles to functioning of humanitarian systems for indemnifying farmer's income
Authors: Saxena Srishti , Singh Manju
Published: February 2025

Purpose

The study examines the production, operational, technological, environmental, economic and financial risks affecting agribusinesses. The primary objective is to identify and prioritise the barriers to the humanitarian system's operational dynamics that focus on indemnifying the farmers' income in India.

Design/methodology/approach

The integrated interpretive structural modelling (ISM)-fuzzy analytical network process (FANP) approach systematically analyses the dynamic interrelationships among barriers, offering a comprehensive framework for agribusiness risk management. The barriers are identified by synthesising literature with the PSALSAR framework. The 18 barriers are clustered into five groups based on phases: planning, designing, execution, implementation and disbursement. The ISM constructs structural hierarchies to identify the interactions among these barriers, while FANP quantifies and establishes the interlinkages between them.

Findings

The proposed model's results reveal that “Skewed Stakeholder Engagement and Data-Deficient Ecosystem” are the most severe barriers to the humanitarian system's operational dynamics. By highlighting the significance of these obstacles, the study contributes to a targeted approach for optimizing resource allocation and enhancing the resilience of humanitarian operations.

Research limitations/implications

Findings enable decision-makers to design more effective interventions and improve operational workflows, particularly essential in contexts with limited resources and pressing time constraints. The study suggests collaboration between humanitarian organisations, governments and stakeholders in developing strategies for addressing barriers.

Originality/value

The study investigates barriers to the dynamic settings of humanitarian operations within the agricultural sector. The research employs a novel approach to analysing the barriers across the various phases of the humanitarian system operating in distinct political, environmental and social settings.
Effect of insitu texture formed by removing spherical graphite on tribological properties of ductile cast iron
Authors: Yuan Wei , Wang Nannan , Guo Qianjian , Wang Wenhua , Chi Baotao , Yan Angang , Yu Jie
Published: February 2025

Purpose

The high-load operation of the engine crankshaft causes severe wear and fatigue. This study aims to prepare in situ textures with effective density and study their wear mechanism on the surface of ductile cast iron, which optimizes the tribological properties of engine crankshafts and reduces wear.

Design/methodology/approach

A new method was proposed based on the hardness difference in graphite removal to form an in situ texture. The friction performance was evaluated using a combination of computational fluid dynamics and tribological testings. The influence of the texture characteristic parameters on the bearing capacity of the oil film was analyzed. The surface wear morphology was studied by scanning electron microscopy.

Findings

The texture density significantly affected the oil film bearing capacity. The surface texture can reduce the average friction coefficient (COF) by more than 35% owing to the oil film bearing and storage capacity. Specifically, the 13% texture density exhibited the lowest wear rate and COF under all three experimental conditions. The reduction in abrasive particles in the wear area of the textured surface indicates that the surface texture can improve the lubrication mechanism.

Originality/value

This study systematically explored the influence of the weight of each model parameter on tribological properties. Subsequently, focusing on the critical parameter (texture density), detailed tribological testings were carried out to reveal the specific effect of texture density on the wear mechanism under different working conditions, and the optimal texture density to achieve the optimal tribological performance was determined accordingly.
Preparation of poly (butylene adipate‐co‐terephthalate)/clove essential oil composite antimicrobial film as biodegradable packaging for strawberry preservation
Authors: Xue Longqian , Zhang Bo , Xiao Douxin , Dong Alideertu
Published: February 2025

Polybutylene adipate terephthalate (PBAT) offers a promising solution to reduce reliance on plastics that do not degrade. In this study, PBAT‐EC‐ATBC composite antimicrobial film (PEC) was prepared by incorporating clove essential oil (CEO) into a casting solution consisting of PBAT and ethyl cellulose (EC). The mechanical property tests revealed that as the content of CEO increased, the tensile strength of the film decreased from 10.10 MPa to 1.86 MPa, and the elongation at break of the film decreased from 886.07% to 540.06%. The optical transmittance tests demonstrate that the incorporation of CEO into films leads to an enhancement from 79% to 86% at 800 nm in optical transmittance. The results demonstrated that the PEC films exhibited excellent bacteriostatic properties, with inhibition zones of 7.47 mm and 9.48 mm against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively. The experimental results demonstrate that the weight loss of strawberries can be reduced to 20% as the CEO content increases and the application of a film can effectively extend the shelf life of strawberries. Furthermore, it was observed that the PEC films displayed favorable degradability characteristics, with the degradation rate of PEC‐6 film reaching 51.71% on Day 19.

Practical Application

A biodegradable film with antimicrobial properties has been developed to effectively extend the shelf life of strawberries. The incorporation of clove essential oil into the film not only enhances its resistance against Escherichia coli and Staphylococcus aureus, but also exerts a pronounced impact on strawberry preservation. This novel antimicrobial composite film exhibits significant potential in the realm of food packaging materials.
Evaluation of the Efficacy and Safety of Transjugular Intrahepatic Portosystemic Shunt Combined With Concurrent Antegrade Embolization of Large Spontaneous Portosystemic Shunts
Authors: Wang Ze , Xu Xiao‐Yang , Liu Chen‐You , Huang Jin‐Tao , Li Wan‐Ci , Zhang Shuai , Shen Jian , Zhong Bin‐Yan , Zhu Xiao‐Li
Published: February 2025

Objectives

To compare the long‐term efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with concurrent antegrade embolization in treating portal hypertension with oesophagogastric variceal bleeding in patients with and without large spontaneous portosystemic shunts (L‐SPSSs).

Materials and Methods

We retrospectively analysed data from patients with portal hypertension who underwent TIPS from November 2015 to April 2022. The patients were screened according to the inclusion criteria and were divided into L‐SPSSs group (L‐S group) and Non L‐SPSSs group (Non L‐S group). The primary outcome was the 2‐year liver transplantation‐free survival (TFS) rate. Secondary outcomes contained the incidence of overt hepatic encephalopathy (OHE), ectopic embolization and the 2‐year rebleeding rate.

Results

A total of 259 patients were enrolled (64 patients in L‐S group and 195 patients in Non L‐S group). The average age was 57.2 years, and the success rate of procedure was 100%. Baseline data showed no significant differences between two groups. There was a statistically significant difference in the 2‐year liver transplantation‐free rate between two groups (L‐S vs. Non L‐S, 84.38% vs. 71.28%; p = 0.045). OHE occurred in 19 (29.69%) patients with L‐SPSSs and 104 (53.33%) patients without L‐SPSSs, with a statistically significant difference (p = 0.001). And no statistically significant difference was found in ectopic embolism incidence rate and the 2‐year rebleeding rate between two groups. Multivariate Cox regression analysis identified male gender, portal vein thrombosis and preoperative high blood ammonia levels as independent risk factors for long‐term survival.

Conclusion

Compared to Non L‐S group, the patients in L‐S group achieve longer liver transplantation‐free survival and lower incidence rate of OHE without increasing the risk of 2‐year rebleeding and ectopic embolization.
Shaping the Future: Analysing Early Childhood Education Policy Reforms and Development in China
Authors: Zhang Jing
Published: February 2025

Early childhood education (ECE) is a crucial component of a child's development, laying the foundation for lifelong learning, well‐being and success. This paper aims to shed light on the evolution of ECE development in China over the years, focusing on how various policies and reforms have influenced its trajectory. This study examines the context and progression of ECE in China through a comprehensive review of the literature and an analysis of online policy documents. The qualitative methodology of Bowen (2009) has been employed for documentary analysis, allowing for an in‐depth exploration of the country's historical context, policy developments and current state of ECE. The historical analysis reveals the significant milestones in China's ECE development, highlighting governmental priorities and educational philosophies shifts over different periods. Policy developments are scrutinised to understand their impact on the accessibility, quality and inclusiveness of ECE. Despite advancements in ECE over the years, the study acknowledges the challenges and limitations of implementing ECE policies. Issues such as regional disparities, resource allocation and the need for professional development for educators are identified as ongoing obstacles. The study emphasises that while key policies have significantly shaped the landscape of ECE, effective implementation requires addressing these multifaceted challenges. In conclusion, the paper underscores the importance of greater collaboration between the government, educators, parents and communities to create a more inclusive and responsive ECE system. Such collaboration is essential for addressing the complex challenges facing ECE and ensuring that all children, regardless of socioeconomic background, have access to high‐quality early education. The findings suggest that a holistic approach, integrating health, education and social policies, is vital for the sustainable development of ECE in China.
High temperature stability of SiC/mullite mini composites
Authors: Zhang Wei , Ma Qingsong , Zeng Kuanhong , Mao Weiguo
Published: February 2025

To clarify the failure behavior of SiC/mullite composites, the microstructure, micro‐ and macro‐mechanical properties of the mini composites after annealing were investigated to estimate the high temperature stability. The as‐received composites presented favorable flexural strength (∼629.6 MPa) and applicable interfacial bonding strength (∼26.2 MPa). The composites exhibited well high temperature stability at the temperature not exceeded 1400°C. Meanwhile, SiC fiber and mullite displayed relatively stable micro mechanical properties. The enhanced interfacial bonding strength caused by the further shrinkage of mullite matrix during annealing was responsible for the decreased flexural strength of the composites. The carbothermal reduction between SiC fiber and mullite matrix occurred at 1500°C, the microstructure of the composites was damaged and a strong chemical bonding formed. Consequently, the annealed composites showed remarkable weight loss and mechanical properties degradation.