bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanoresponsive regulation of tissue regeneration during distraction osteogenesis
Authors: Hu Wenzhong , Guo Zeyou , Tang Weibing , Long Jie 
Published: September 2024

AbstractDistraction osteogenesis is widely used for bone tissue engineering. Mechanical stimulation plays a central role in the massive tissue regeneration observed during distraction osteogenesis. Although distraction osteogenesis has been a boon for patients with bone defects, we still have limited knowledge about the intrinsic mechanotransduction that converts physical forces into biochemical signals capable of inducing cell behavior changes and new tissue formation. In this review, we summarize the findings for mechanoresponsive factors, including cells, genes, and signaling pathways, during the distraction osteogenesis different phases. These elements function for coupling of osteogenesis and angiogenesis via the Integrin‐FAK, TGF‐β/BMP, Wnt/β‐catenin, Hippo, MAPK, PI3K/Akt, and HIF‐1α signaling pathways in a mechanoresponsive niche. The available evidence further suggests the existence of a balance between the epithelial–mesenchymal transition and mesenchymal–epithelial transition under hypoxic stress. We also briefly summarize the current in silico simulation algorithms and propose several future research directions that may advance understanding of distraction osteogenesis in the era of bioinformation, particularly the integration of artificial intelligence models with reliable single‐cell RNA sequencing datasets. The objective of this review is to utilize established knowledge to further optimize existing distraction protocols and to identify potential therapeutic targets.
Effects of Serratus Anterior Plane Block on Early Recovery from Thoracoscopic Lung Resection: A Randomized, Blinded, Placebo-controlled Trial
Authors: Jackson Jacob C. , Tan Kay See , Pedoto Alessia , Park Bernard J. , Rusch Valerie W. , Jones David R. , Zhang Hao , Desiderio Dawn , Fischer Gregory W. , Amar David 
Published: September 2024

Background:
The efficacy of serratus anterior plane block for treatment of pain after minimally invasive thoracic surgery remains unclear. This trial assesses the impact of serratus anterior plane block on postoperative opioid consumption and on measures of early recovery after thoracoscopic lung resection.

Methods:
Patients undergoing minimally invasive anatomic lung resection at a single center were randomized to undergo serratus anterior plane block with 40 ml injectate containing bupivacaine 0.25%, clonidine 100 μg, and dexamethasone 4 mg (serratus anterior plane block group) or sham block with 40 ml normal saline (placebo group) at the conclusion of surgery. The primary outcome was cumulative intravenous morphine equivalents during the first 24 h postoperatively. Secondary outcomes were intravenous morphine equivalents, pain scores at rest and with cough, inspiratory volume on incentive spirometry, incidence of nausea or vomiting during the first 48 h postoperatively, Quality of Recovery–15 score on postoperative day 7, and length of stay.

Results:
Using the protocol-specified intention-to-treat analysis, the median (interquartile range) intravenous morphine equivalents was 10.6 (5.0 to 27.1) mg in serratus anterior plane block patients (n = 46) versus 18.8 (9.9 to 29.6) mg in placebo patients (n = 46; 32% reduction; ratio, 0.68 [95% CI, 0.44 to 1.06]; P = 0.085). Of the secondary outcomes, only the composite pain with cough scores differed significantly in the serratus anterior plane block group by a coefficient of –0.41 (95% CI, –0.81 to –0.01; P = 0.044). A sensitivity as-treated analysis reported median (interquartile range) intravenous morphine equivalents of 10.0 (5.0 to 27.2) mg in serratus anterior plane block patients (n = 44) versus 19.9 (10.4 to 29.0) mg in placebo patients (n = 48; 36% reduction; ratio, 0.64 [95% CI, 0.41 to 1.00]; P = 0.048).

Conclusions:
The protocol-specified intention-to-treat analysis demonstrated that serratus anterior plane block did not result in a significant reduction in opioid consumption when added to a multimodal analgesic regimen after thoracoscopic anatomic lung resection. The sensitivity as-treated analysis showed a significant and modest clinical reduction in the primary outcome that warrants further investigation.
Koby Superficial Reticular Degeneration of the Cornea
Authors: Koulouri Ismini , Park Jennifer 
Published: September 2024

Purpose:
Corneal reticular degeneration of Koby, a rare corneal degeneration, has not been previously reported in association with sarcoidosis. We report such a case presenting to our clinic after a prolonged course of bilateral panuveitis secondary to sarcoidosis.

Methods:
A 58-year-old woman with a history of chronic panuveitis secondary to sarcoidosis presented with new visual disturbances and the rare finding of superficial corneal reticular degeneration of Koby. The clinical presentation, diagnosis, and management of this unique ocular manifestation are discussed.

Results:
Corneal reticular degeneration of Koby is most likely a subvariant of band keratopathy that has been very rarely reported in the literature to date and not yet reported as a complication of sarcoidosis.

Conclusions:
Clinicians should be aware of this presentation of band keratopathy in patients and be able to recognize and treat it accordingly.
Multimodal Imaging of Posterior Corneal Opacities in Multicentric Osteolysis Nodulosis and Arthropathy
Authors: Eppley Sarah E. , Pasricha Neel D. , Seitzman Gerami D. , Joye Ashlin , Arboleda Alejandro , Qureshi Azam 
Published: September 2024

Purpose:
Multicentric osteolysis nodulosis and arthropathy (MONA) syndrome is a rare autosomal recessive skeletal dysplasia. Caused by mutations in the matrix metalloproteinase 2 (MMP2) gene on chromosome 16q12, this syndrome has infrequently been associated with ophthalmic manifestations. Corneal opacities have been reported but not described or documented in detail.

Methods:
Complete ophthalmologic examination and multimodal anterior segment imaging were used to characterize the corneal findings in a patient with MONA syndrome.

Results:
A 19-year-old man with MONA syndrome was referred for an eye examination based on MONA screening recommendations. Visually insignificant peripheral corneal opacities were noted. Anterior segment optical coherence tomography demonstrated posterior stromal and endothelial hyperreflectivity. Confocal microscopy demonstrated an acellular peripheral endothelium with a normal central endothelium.

Conclusions:
Corneal opacities can occur with MONA syndrome, which is caused by mutations in the MMP2 gene. In the patient presented here, the corneal opacities are peripheral, deep stromal, with sparing of the anterior stroma and epithelium.
Left Middle Phalanx Tuberculous Dactylitis Masquerading as a Tumor: First Case Report in Saudi Arabia
Authors: Nukaly Houriah Yasir , Ahmed Ruqayyah Ali , Mousa Ahmed Hafez , Moallem Adnan Anas , Zubair Mohammed Talha Mohammed , AlAidarous Hasan Ali Abdullah , Alshanberi Asim Muhammed , Albalawi Ibrahim Abdullah S. , Abbas Fahad 
Published: September 2024

Summary:
Tuberculous dactylitis can cause osteomyelitis, which is a rare extrapulmonary manifestation of tuberculosis, often misdiagnosed due to its nonspecific presentation and resemblance to other conditions like neoplasms. A 15-year-old male patient reported to our clinic with a 1-year history of left index finger pain and swelling following a football-related injury. Despite conservative management, the symptoms had progressively worsened over the past few months. Clinical examination revealed deformity and swelling of the middle phalanx, along with induced pain on range of motion. Bacteriological analysis indicated polymorphic nuclear cells and the presence of coagulase-negative Staphylococcus (Staphylococcus hominis). Radiographic evaluation, including x-ray and magnetic resonance imaging, revealed medullary expansion, trabecular thinning, and focal soft tissue swelling. Magnetic resonance imaging displayed extensive soft tissue and bone marrow involvement, raising concerns of a tumor. An open biopsy was performed, yielding unexpected findings of necrotizing and suppurative granulomatous inflammation, strongly suggesting an ongoing infectious process. The subsequent Quantiferon TB Gold Test confirmed tuberculosis infection. Treatment encompassed debridement, synovectomy, and initiation of an antituberculosis regimen. The patient showed significant improvement after treatment. Timely diagnosis and treatment of tuberculous dactylitis are crucial, as highlighted by the patient’s positive response to combined surgical and pharmacological intervention, despite initial diagnostic challenges.
Evidence-Based Review of Randomized Controlled Trials of Interventions for the Management of Behavioral Issues in Individuals With Moderate to Severe Traumatic Brain Injury
Authors: MacKenzie Heather M. , Flores-Sandoval Cecilia , Bateman Emma A. , McIntyre Amanda , Barua Ujjoyinee , Mehta Swati , Bayley Mark , Teasell Robert 
Published: September 2024

Objective:
To present an evidence-based review of randomized controlled trials (RCTs) evaluating interventions for the management of behavioral issues post moderate to severe traumatic brain injury (MSTBI), as part of an extensive database that has been conceptualized as a living systematic review.

Methods:
Systematic searches were conducted in MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO, up to and including December 2022, for articles published in the English language, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of RCT was assessed using the Physiotherapy Evidence Database (PEDro) scale, and level of evidence was assigned using a modified Sackett scale.

Results:
Forty-six RCTs examining interventions and outcome measures related to behavioral issues post-MSTBI were included. These studies collectively enrolled 3,267 participants. The majority of RCTs were conducted in the United States (n = 27; 58.7%) and 28 (60.9%) were conducted after 2010. Of these, 27 RCTs examined non-pharmacological interventions and 19 examined pharmacological interventions. Effective pharmacological treatments included amantadine and dexmedetomidine. Effective non-pharmacological interventions included sensory stimulation in the acute phase, anger self-management programs, peer mentoring, problem-solving, and emotional regulation. Psychotherapy showed conflicting evidence.

Conclusion:
This evidence-based review provides a comprehensive overview of the research landscape of RCTs addressing behavior post-MSTBI. The findings from these RCTs may be valuable for health care professionals, researchers, and policymakers involved in the field of TBI and behavior.
Racial, ethnic, and sex bias in large language model opioid recommendations for pain management
Authors: Young Cameron C. , Enichen Elizabeth , Rao Arya , Succi Marc D. 
Published: September 2024

Abstract
Understanding how large language model (LLM) recommendations vary with patient race/ethnicity provides insight into how LLMs may counter or compound bias in opioid prescription. Forty real-world patient cases were sourced from the MIMIC-IV Note dataset with chief complaints of abdominal pain, back pain, headache, or musculoskeletal pain and amended to include all combinations of race/ethnicity and sex. Large language models were instructed to provide a subjective pain rating and comprehensive pain management recommendation. Univariate analyses were performed to evaluate the association between racial/ethnic group or sex and the specified outcome measures—subjective pain rating, opioid name, order, and dosage recommendations—suggested by 2 LLMs (GPT-4 and Gemini). Four hundred eighty real-world patient cases were provided to each LLM, and responses included pharmacologic and nonpharmacologic interventions. Tramadol was the most recommended weak opioid in 55.4% of cases, while oxycodone was the most frequently recommended strong opioid in 33.2% of cases. Relative to GPT-4, Gemini was more likely to rate a patient's pain as “severe” (OR: 0.57 95% CI: [0.54, 0.60]; P < 0.001), recommend strong opioids (OR: 2.05 95% CI: [1.59, 2.66]; P < 0.001), and recommend opioids later (OR: 1.41 95% CI: [1.22, 1.62]; P < 0.001). Race/ethnicity and sex did not influence LLM recommendations. This study suggests that LLMs do not preferentially recommend opioid treatment for one group over another. Given that prior research shows race-based disparities in pain perception and treatment by healthcare providers, LLMs may offer physicians a helpful tool to guide their pain management and ensure equitable treatment across patient groups.
Predictors of Prolonged Hospital Stay After Microsurgery for Vestibular Schwannoma: Analysis of a Decade of Data
Authors: Aboueisha Mohamed A. , Manayan Regan , Tie Kevin , Issa Peter P. , Al-Hamtary Mohamed A. , Huang Victoria , Naples James G. 
Published: September 2024

Importance
Microsurgical resection is one of the treatments for vestibular schwannomas (VS). While several factors have been linked to increased length of stay (LOS) for VS patients undergoing microsurgery, a better understanding of these factors is important to provide prognostic information for patients.

Objective
Determine predictors of increased LOS for VS patients undergoing microsurgical resection.

Design
Retrospective analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2010 to 2020.

Setting
Database review

Participants
All patients who underwent microsurgery (CPT codes 61520, 61526/61596) for the management of vestibular schwannoma (ICD9 and ICD10 codes 225.1, D33.3) were included.

Main Outcomes and Measures
Analyzing perioperative factors that can predict prolonged hospital stay

Results
A total of 2096 cases were identified and 1,188 (57%) of these patients were female. The mean age was 51.0 ± 14.0 years. Factors contributing to prolonged LOS included African American race (OR = 2.11, 95% CI: 1.32–3.36, p = 0.002), insulin-dependent diabetes mellitus (OR = 2.12, 95% CI: 1.09–4.4.11, p = 0.026), hypertension (OR = 1.26, 95% CI: 1–1.58, p = 0.046), functional dependency (OR = 5.22, 95% CI: 2.31–11.79, p = 0.001), prior steroid use (OR = 1.96, 95% CI: 1.18–3.15, p = 0.009), ASA class III (OR = 2.06, 95% CI: 1.18–3.6, p < 0.011), ASA class IV (OR = 6.34, 95% CI: 2.62–15.33, p < 0.001), and prolonged operative time (OR = 2.14, 95% CI: 1.76–2.61). Microsurgery by a translabyrinthine (TL) approach compared to a retrosigmoid (RSG) approach had lower odds of prolonged LOS (OR = 0.67, 95% CI: 0.54–0.82, p < 0.001). In a separate analysis regarding patients receiving reoperation, operative time was the only predictor of prolonged LOS (OR = 2.77, 95% CI: 1.39–5.53, p = 0.004.)

Conclusions and Relevance
Our analysis offers an analysis of the factors associated with a prolonged LOS for the surgical management of VS. By identifying healthcare disparities, targeting modifiable factors, and applying risk stratification based on demographics and comorbidities, we can work toward reducing disparities in LOS and enhancing patient outcomes.
Association of smoking with neurocognition, inflammatory and myeloid cell activation profiles in people with HIV on antiretroviral therapy
Authors: Yadav Anjana , Gionet Gabrielle , Karaj Antoneta , Kossenkov Andrew V. , Kannan Toshitha , Putt Mary E. , Stephens Shields Alisa J. , Ashare Rebecca L. , Collman Ronald G. 
Published: September 2024

Objective:
People with HIV (PWH) experience excess comorbidities, including neurocognitive disorders, which are linked to inflammation, particularly monocyte–macrophage activation. Smoking contributes to morbidity and mortality in well treated PWH. We investigated associations between smoking, neurocognitive function, and inflammation in PWH on antiretroviral therapy (ART).

Design:
We used baseline data on cognition and inflammation from a longitudinal study of virologically suppressed PWH who do and do not smoke.

Methods:
Participants completed four neurocognitive tests (seven measures), with a composite score as the primary measure. Inflammatory markers were plasma sCD14, sCD163, and CCL2/MCP-1; %CD14+ monocytes expressing CD16, CD163, and CCR2; and %CD8+ T cells co-expressing CD38/HLA-DR. Exploratory analyses included a plasma cytokine/chemokine panel, neurofilament light chain (NFL), hsCRP, and monocyte transcriptomes by RNAseq.

Results:
We recruited 58 PWH [26 current smoking (PWH/S), 32 no current smoking (PWH/NS)]. Mean composite and individual neurocognitive scores did not differ significantly by smoking status except for the color shape task; PWH/S exhibited worse cognitive flexibility, with adjusted mean times 317.2 [95% confidence interval (CI) 1.4–632.9] ms longer than PWH/NS. PWH/S had higher plasma sCD14 than PWH/NS [median (IQR) 1820 (1678–2105) vs. 1551 (1284–1760) ng/ml, P = 0.009]. Other inflammatory markers were not significantly different between PWH/S and PWH/NS. Monocyte transcriptomes showed several functions, regulators, and gene-sets that differed by smoking status.

Conclusion:
sCD14, a marker of monocyte activation, is elevated in PWH who smoke. Although neurocognitive measures and other inflammatory markers did not generally differ, these data implicate smoking-related myeloid activation and monocyte gene dysregulation in the HIV/smoking synergy driving HIV-associated comorbidities.
In vivoquantification of creatine kinase kinetics in mouse brain using31P-MRS at 7 Tesla
Authors: Tachrount Mohamed , Smart Sean , Lerch Jason , Cherix Antoine 
Published: September 2024

Abstract31P-MRS is a method of choice for studying neuroenergeticsin vivo, but its application in the mouse brain have been limited, often restricted to ultra-high field (>7 Tesla) MRI scanners. Establishing its feasibility on more readily available preclinical 7 Tesla (T) scanners would create new opportunities to study metabolism and physiology in murine models of brain disorders. Here, we demonstrate that the apparent forward rate constant (kf) of creatine kinase (CK) can be accurately quantified using a progressive saturation-transfer approach in the mouse brain at 7T. We also find that a reduction of approximately 20% in the breathing rate of anesthetized mice can lead to a 36% increase in kfattributable to a drop in intracellular pH and mitochondrial ATP production. To achieve this, we used a test-retest analysis to assess the reliability and repeatability of31P-MRS acquisition, analysis and experimental design protocols. We report that most31P-containing metabolites can be reliably measured using a localized 3D-ISIS sequence, which showed highest SNR amplitude, SNR consistency and minimal T2relaxation signal loss. Using this protocol, our study identifies, for the first time, key physiological factors influencing mouse brain energy homeostasisin vivoand provides a methodological basis that will guide future studies interested in implementing31P-MRS on preclinical 7T scanners.
Structure – silencing duration relationships in RNAi medicines in rapidly dividing cells
Authors: Kremer Anastasia , Ryaykenen Tatyana , Segarra-Visent Xavier , Sauer Melanie , Tang Qi , Cooper David A , Echeverria Dimas , Philouze Clothilde , Bayon Emilie , Georgess Dan , Haraszti Reka A 
Published: September 2024

AbstractRNA interference (RNAi)-based medicines offer precise targeting of virtually any transcript, making them an appealing new drug class for addressing unmet needs in immune-oncological applications. While RNAi therapies show exceptional duration of effect in non-dividing cells, their efficacy in rapidly dividing cells, crucial for immune-oncology, remains largely unexplored. Unlike in non-dividing cells, full chemical modification in rapidly dividing cells has not consistently extended silencing duration, according to limited data available.In this study, we investigated key factors affecting the duration of effect for three main types of RNAi-based therapeutics (siRNA, miRNA mimics, and miRNA inhibitors) in rapidly dividing cancer and immune cells. Saturation of intracellular depots by multiple loading doses, a common strategy to prolong silencing duration in non-dividing hepatocytes, had minimal impact on siRNA duration of effect in rapidly dividing cells. However, modifying the antisense strand with a 5’-(E)-vinylphosphonate (5’-VP) to protect siRNAs from exonucleases and enhance AGO2 binding significantly extended siRNA silencing duration to over 30 days bothin vitroandin vivo. For miRNA mimics, extensive stabilization of the antisense strand with phosphorothioates was not effective and led to reduced potency and silencing duration. Interestingly, a shorter duplex region commonly seen in therapeutic siRNAs partially rescued duration of silencing in miRNA mimics with extended phosphorothioate modifications. On the other hand, miRNA inhibitors demonstrated robust reversal of miRNA activity for an impressive 25 days in cancer cell lines.Our findings enable the rational design of the chemical architecture and administration regimens of RNAi-based therapies in oncology and immunology.
The new phycobilisome linker protein ApcI regulates high light adaptation inSynechocystissp. PCC 6803
Authors: Espinoza-Corral Roberto , Zavřel Tomáš , Sutter Markus , Leslie Chase H. , Yang Kunwei , Beck Warren F. , Červený Jan , Kerfeld Cheryl A. 
Published: September 2024

AbstractPhycobilisomes are versatile cyanobacterial antenna complexes that harvest light energy to drive photosynthesis. These complexes can also adapt to various light conditions, dismantling under high light to prevent photo-oxidation and arranging in rows under low light to increase light harvesting efficiency. Light quality also influences phycobilisome structure and function, as observed under far-red light exposure. Here we describe a new, phycobilisome linker protein, ApcI (previously hypothetical protein sll1911), expressed specifically under red light. We characterized ApcI inSynechocystissp. PCC 6803 using mutant strain analyses, phycobilisome binding experiments, and protein interaction studies. Mutation ofapcIconferred high light tolerance toSynechocystissp. PCC 6803 compared to wild type with reduced energy transfer from phycobilisomes to the photosystems. Binding experiments revealed that ApcI replaces the linker protein ApcG at the membrane-facing side of the phycobilisome core using a paralogous C-terminal domain. Additionally, the N-terminal extension of ApcI was found to interact with photosystem II. Our findings highlight the importance of phycobilisome remodeling for adaptation under different light conditions. The characterization of ApcI provides new insights into the mechanisms by which cyanobacteria optimize light-harvesting in response to varying light environments.