bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of waste processing between MASARO plastic refinery unit and maggots technology
Authors: Steven S , Dwiputra G A , Affan M K A , Soekotjo E S A , Syamsudin E , Nadirah N , Sasongko N A , Yemensia E V , Abidin A Z
Published: June 2024

The evaluation of MASARO plastic refinery unit and maggots waste processing strategies’ efficacy, environmental impact, and economic analysis is at the center of the issue formulation in this study. Waste processing through MASARO plastic refinery unit requires incinerators, pyrolysis, and wet scrubber units. On the other side, maggots are used in waste processing because of their capacity to swiftly degrade the waste without negative impacts on the environment. Waste reduction is a parameter that can be used to measure the performance of waste processing. The percentages of waste reduction achieved by using MASARO plastic refinery unit can surpass 90% whereas maggots can range from 65.5% to 78.9%. The environmental impacts of MASARO plastic refinery unit and maggots technology are low. The flue gas qualities from MASARO plastic refinery unit are almost below threshold limits so it does not harm the environment. Likewise, waste processing using maggots has almost no negative impacts due to low emissions of CO2, CH4, SO2, and N-element. From an economic point of view, the MASARO process can provide an annual revenue of $3,840,000. Meanwhile, the anticipated annual revenue from waste processing using maggots is $55,000 if they are sold for $1000 per ton.
The Humane Perspective
Authors: Cottingham John
Published: June 2024

This introductory chapter, specially written for the volume, describes the overall aims of the book. It explains how the ‘humane philosophy’ agenda aims to be grounded in the realities of human practice and performance, and pervasively informed by experiential engagement with those realities. It references the work of Iain McGilchrist, Bernard Williams, Sigmund Freud, Martha Nussbaum, Eleonore Stump, and Judith Wolfe, in arguing for a more emotionally and imaginatively engaged form of philosophy, which goes beyond abstract argumentation so as to draw on all the resources available the human mind. As an appendix to the chapter, there is a conspectus of the volume, setting out its main sections—‘Manifesto and Method’; ‘Morality and Meaning’; ‘Science and its Limits’; and ‘Reaching for the Transcendent’—and providing an overview of the argument in each of the chapters.
Happiness, Temporality, and Meaning
Authors: Cottingham John
Published: June 2024

This chapter argues that there is an implicit temporal or diachronic dimension in ascriptions of happiness, and that assessments of happiness involve evaluating a whole human life. The contribution to happiness of a given episode depends on its fitting into a pattern of moral significance, so that it can be seen retrospectively as constituting a stage in the individual’s growth towards fulfilment. A further stage in the argument draws on the Freudian notion of Nachträglichkeit, which conveys the idea of something’s being ‘carried over’ from the past, with the added implication that something is retroactively ‘added on’. If the full significance of key events in life is often only available retrospectively, this casts doubt on traditional philosophical models of happiness based on autonomous planning and rational self-sufficiency. A more psychologically nuanced approach, acknowledging our human vulnerability, may open the way to a richer conception of happiness.
Conversion, Self-Discovery, and Moral Change
Authors: Cottingham John
Published: June 2024

This chapter examines the idea of conversion, which is seldom an uncomplicated progression in virtue, but often arises from the sense of an objective ethical demand requiring the direction of life to change. In the ‘psycho-ethical dynamics’ of conversion, the emotions typically play a role in ‘unblocking’ the resistance to change. Such radical moral ‘rebirth’ appears favourably when contrasted first with the picture of ethical development found in Aristotelian virtue theory, and, second, with modern secular accounts such as that of André Compte-Sponville, where submission to an external demand is replaced by the liberation of the ego as autonomous determiner of the good. The chapter points in conclusion to analogies between the psychotherapeutic goal of liberating us from infantile projections so that we can confront the therapist without evasion, and the religious idea of God as the compassionate Other, before whom one must present oneself in wholeness of being.
Brain Laterality and Religious Awareness
Authors: Cottingham John
Published: June 2024

Iain McGilchrist’s study The Master and His Emissary examines the roles of the left and right hemispheres of the brain in different kinds of mental capacities, and goes on to distinguish two corresponding ways of relating to the world, an ‘abstracted’ mode and a ‘connected’ mode. This chapter asks what philosophical conclusions should be drawn from this (a question that necessarily takes us outside the domain of science). Pointing to the bilateral workings of the brain should reduce the temptation to see consciousness as an indivisible centre of awareness to which we have transparent access. The detached, analytic, ‘left-brain’ view of a phenomenon should never be mistaken for a fully adequate grasp of its significance, and this should affect the way we philosophize about religion. In striving to understand the nature of the reality surrounding us, both modes of relating to the world, the analytic and the intuitive, are essential.
Engagement, Immersion, and Enactment
Authors: Cottingham John
Published: June 2024

This final chapter takes up the previously discussed notion of modes of awareness that depend on engagement and involvement, and relates it to the role of praxis in shaping a religious outlook. Philosophical argument may sometimes generate religious belief, but the transformative effect of spiritual praxis is often more significant. Examining this process helps us to see how religious belief and spiritual practice are related: the latter works on us not just intellectually, but emotionally and physically, in a multi-layered, holistic way that engages the whole person. It allows us, instead of scrutinizing a worldview from a distance, to immerse ourselves in it so that, through imaginative identification, it becomes a fundamental part of who we are. In spiritual praxis we are able to enact our longing for the good, thereby coming as close as our finite human nature allows to encountering the infinite perfection that eludes complete philosophical understanding.
The genetic etiology is a relevant cause of central precocious puberty
Authors: Canton Ana Pinheiro Machado , Seraphim Carlos Eduardo , Montenegro Luciana Ribeiro , Krepischi Ana Cristina Victorino , Mendonca Berenice Bilharinho , Latronico Ana Claudia , Brito Vinicius Nahime
Published: June 2024

Objectives

The etiology of central precocious puberty (CPP) has expanded with identification of new genetic causes, including the monogenic deficiency of Makorin-Ring-Finger-Protein-3 (MKRN3). We aimed to assess the prevalence of CPP causes and the predictors of genetic involvement in this phenotype.

Design

A retrospective cohort study for an etiological survey of patients with CPP from a single academic center.

Methods

All patients with CPP had detailed medical history, phenotyping, and brain magnetic resonance imaging (MRI); those with negative brain MRI (apparently idiopathic) were submitted to genetic studies, mainly DNA sequencing studies, genomic microarray, and methylation analysis.

Results

We assessed 270 patients with CPP: 50 (18.5%) had CPP-related brain lesions (34 [68%] congenital lesions), whereas 220 had negative brain MRI. Of the latter, 174 (165 girls) were included for genetic studies. Genetic etiologies were identified in 22 patients (20 girls), indicating an overall frequency of genetic CPP of 12.6% (22.2% in boys and 12.1% in girls). The most common genetic defects were MKRN3, Delta-Like-Non-Canonical-Notch-Ligand-1 (DLK1), and Methyl-CpG-Binding-Protein-2 (MECP2) loss-of-function mutations, followed by 14q32.2 defects (Temple syndrome). Univariate logistic regression identified family history (odds ratio [OR] 3.3; 95% CI 1.3-8.3; P = .01) and neurodevelopmental disorders (OR 4.1; 95% CI 1.3-13.5; P = .02) as potential clinical predictors of genetic CPP.

Conclusions

Distinct genetic causes were identified in 12.6% patients with apparently idiopathic CPP, revealing the genetic etiology as a relevant cause of CPP in both sexes. Family history and neurodevelopmental disorders were suggested as predictors of genetic CPP. We originally proposed an algorithm to investigate the etiology of CPP including genetic studies.
High-Impact Pain Is Associated With Epigenetic Aging Among Middle-Aged and Older Adults: Findings From the Health and Retirement Study
Authors: Tamargo Javier A , Strath Larissa J , Cruz-Almeida Yenisel
Published: June 2024

Background

Chronic pain has been associated with accelerated biological aging, which may be related to epigenetic alterations. We evaluated the association of high-impact pain (ie, pain that limits activities and function) with epigenetic aging, a measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States.

Methods

Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study. Epigenetic aging was derived from 13 epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Ordinary least squares regressions were performed to test for differences in the epigenetic clocks, adjusting for the complex survey design, as well as biological, social, and behavioral factors.

Results

The analysis consisted of 3 855 adults with mean age of 68.5 years, including 59.8% with no pain and 25.8% with high-impact pain. Consistent with its operational definition, high-impact pain was associated with greater functional and activity limitations. High-impact pain was associated with accelerated epigenetic aging compared to no pain, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. Additionally, GrimAge was accelerated in high-impact pain as compared to low-impact pain.

Conclusions

High-impact pain is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. These findings highlight aging-associated epigenetic alterations in high-impact chronic pain and suggest a potential for epigenetic therapeutic approaches for pain management and the preservation of physical function in older adults.
METTL3 Promotes Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration by Regulating TLR2 m6A Methylation and Gut Microbiota
Authors: Ni Shuangfei , Huang Xiusheng , Li Xuesen , Shi Chenhao , Fan Mingzhe , Zhao Lantian , Rong Zijie , Zhang Huafeng
Published: June 2024

Background

Nucleus pulposus cell (NPC) senescence in intervertebral disc (IVD) tissue is the major pathological cause of intervertebral disc degeneration (IDD). N6-methyladenosine (m6A) methylation and gut microbiota play important roles in the progression of IDD. This study investigated whether methyltransferase-like 3 (METTL3) regulates TLR2 m6A modification and gut microbiota to influence NPC senescence.

Methods

An IDD rat model was established by lumbar IVD puncture and NPCs were challenged with IL-1β to mimic IVD injury. IDD rats and IL-1β-exposed NPCs were treated with METTL3-interfering lentivirus and the TLR2 agonist Pam3CSK4. Compositional changes in the rat gut microbiota were analyzed and fecal microbiota transplantation procedures were used. NPC senescence, cell cycle, and the expression of senescence-associated secretory phenotype (SASP) factors were assessed. The m6A enrichment of TLR2 and the binding of IGF2BP1 to TLR2 mRNA were examined.

Results

METTL3 and TLR2 were highly expressed in IDD rats. METTL3 silencing attenuated senescent phenotypes and reduced secretion of SASP factors. Pam3CSK4 reversed the beneficial effects of METTL3 silencing on NPC senescence and IVD injury. METTL3 stabilized TLR2 mRNA in an IGF2BP1-dependent manner. METTL3 silencing restored specific gut microbiota levels in IDD rats, which was further reversed by administration of Pam3CSK4. Fecal microbiota from METTL3 silenced IDD rats altered the pathological phenotypes of IDD rats.

Conclusions

These results demonstrate the beneficial effects of METTL3 silencing on NPC senescence and amelioration of IVD injury, involving modulation of TLR2 m6A modification and gut microbiota. These findings support METTL3 silencing as a potential therapeutic target for IDD.
Baseline Assessment of Serum Cytokines Predicts Clinical and Endoscopic Response to Ustekinumab in Patients With Crohn’s Disease: A Prospective Pilot Study
Authors: Bertani Lorenzo , Antonioli Luca , Fornili Marco , D’Antongiovanni Vanessa , Ceccarelli Linda , Carmisciano Luca , Benvenuti Laura , Mumolo Maria Gloria , Bottari Andrea , Pardi Veronica , Baiano Svizzero Giovanni , Baglietto Laura , De Bortoli Nicola , Bellini Massimo , Fornai Matteo , Costa Francesco
Published: June 2024

Background

No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn’s disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST.

Methods

We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing.

Results

Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001).

Conclusions

This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions.
Claimants and Standing
Authors: Caro de Sousa Pedro
Published: June 2024

This chapter covers the rules on standing for non-contractual liability and the categories of claimants for damages in competition law cases. It explains that the rules on standing for non-contractual liability typically determine who has standing to sue for compensation for competition harm suffered. While rules on causation and standing may be related, they are conceptually distinct. Moreover, economic injuries have a way of rippling through markets, creating larger numbers of victims than a typical contract or tortious dispute, which then creates a broad range of potential claimants. The chapter enumerates direct purchasers, indirect purchasers, and other plaintiffs as different categories of claimants.
Unleashing the power of clinical trial data: a proposal for enhancing informed consent and data sharing
Authors: Trippa Lorenzo , Khozin Sean
Published: June 2024

Although clinical trial participants support data sharing, access to patient-level data remains limited. Innovative solutions are needed to ensure scientists can access the data from clinical trials. This commentary proposes a potential strategy.
Reaction-diffusion modeling provides insights into biophysical carbon-concentrating mechanisms in land plants
Authors: Kaste Joshua A M , Walker Berkley J , Shachar-Hill Yair
Published: June 2024

Carbon-concentrating mechanisms (CCMs) have evolved numerous times in photosynthetic organisms. They elevate the concentration of CO2 around the carbon-fixing enzyme rubisco, thereby increasing CO2 assimilatory flux and reducing photorespiration. Biophysical CCMs, like the pyrenoid-based CCM (PCCM) of Chlamydomonas reinhardtii or carboxysome systems of cyanobacteria, are common in aquatic photosynthetic microbes, but in land plants appear only among the hornworts. To predict the likely efficiency of biophysical CCMs in C3 plants, we used spatially resolved reaction-diffusion models to predict rubisco saturation and light use efficiency. We found that the energy efficiency of adding individual CCM components to a C3 land plant is highly dependent on the permeability of lipid membranes to CO2, with values in the range reported in the literature that are higher than those used in previous modeling studies resulting in low light use efficiency. Adding a complete PCCM into the leaf cells of a C3 land plant was predicted to boost net CO2 fixation, but at higher energetic costs than those incurred by photorespiratory losses without a CCM. Two notable exceptions were when substomatal CO2 levels are as low as those found in land plants that already use biochemical CCMs and when gas exchange is limited, such as with hornworts, making the use of a biophysical CCM necessary to achieve net positive CO2 fixation under atmospheric CO2 levels. This provides an explanation for the uniqueness of hornworts' CCM among land plants and the evolution of pyrenoids multiple times.
Advancements in bioscavenger mediated detoxification of organophosphorus poisoning
Authors: Li Hexi , Lu Cong , Liu Zhenmin , Xiang Fengshun , Liu Bo , Wang Hongjuan , Chang Jie , Pan Li , Chen Youwei , Chen Jingfei
Published: June 2024

Background

Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects.

Objective

This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field.

Methods

A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods.

Results

Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods.

Conclusion

With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.
Christian Worldview and Caring in Nursing
Authors: Osaka Kyoko , Soriano Gil P. , Blaquera Allan Paulo L. , Tanioka Tetsuya , Baua Maria Elizabeth C. , Schoenhofer Savina O. , Ray Marilyn A.
Published: June 2024

Sister Simone Roach, a noted philosopher of caring in nursing, left behind a significant body of theoretical and practical work highlighting the areas of nursing ethics, care/caring, and compassion. This article explores the integration of the moral foundation of agape love in Pauline theology and Roach's human caring in nursing (1992) as the action of agape love. A narrative literature review explores the relationship between the scriptural ethics of St. Paul (Pauline ethics) and Roach's caring in nursing.
Next-generation sequencing identifies the mutational signature of double primary and metastatic malignancies: A case report
Authors: Tang Shiying , Deng Yixiao , Yan Yinan , Bai Jie , He Huiying , Zhang Shudong , Yang Jie , Qiu Min , Tian Xiaojun
Published: June 2024

We present the case of a 59-year-old Chinese man diagnosed with stage III clear cell renal cell carcinoma who developed 2 suspicious lung lesions 5 years after follow-up. Pathological evaluation revealed 2 distinct types of cancer: lung adenocarcinoma in situ and clear cell renal carcinoma with lung metastasis. Lung tissue samples were sequenced using a panel of 1267 cancer-related genes. The analysis revealed completely different molecular profiles between the 2 lung lesions and similar clonal mutations in the superior lingular lobe and kidney. This indicates multiple metachronous primary tumors.
Assessment and Identification of Improvement Areas for Facial Symmetry in Hemifacial Microsomia (Type IIB) Using Three-dimensional Measurements
Authors: Niikura Yoichiro , Ishii Takenobu , Sakamoto Yoshiaki , Ariizumi Dai , Sakamoto Teruo , Sueishi Kenji
Published: June 2024

Background:

Surgical planning for hemifacial microsomia (HFM) patients often involves planning the amount of maxillary movement and mandibular bone distraction from three-dimensional (3D) volumetric images constructed from computed tomography scans. By representing anatomical indicators for facial symmetry in X, Y, and Z coordinates, we identified the more challenging areas in correcting facial asymmetry.

Methods:

The study included five HFM patients with a mean age of 22.2 years, all diagnosed with HFM (type IIB). We established measurement points with high reproducible 3D coordinates on the 3D volumetric images obtained from computed tomography scans for before surgery, treatment objectives, and after surgery. We assessed the symmetry of measurement points between the affected side and nonaffected side at each time point.

Results:

In the before-surgery group, significant differences were observed between the affected side and nonaffected side in X,Y (excluding Palatine foramen, upper molar, canine) and Z coordinates for measurement items. In the treatment objectives group, no differences were observed between the affected side and nonaffected side in X, Y, and Z coordinates, resulting in facial symmetry. In the after-surgery group, significant differences were observed in Y coordinates in the mental foramen area, and significant differences were observed in z axis measurement items in the canine and mental foramen areas.

Conclusions:

It is evident that relying solely on a front view assessment is insufficient to achieve facial symmetry. Particularly, both anterior–posterior and vertical improvements in the area near the mental foramen on the affected side are necessary.
Proximal Bilateral Arm Transplantation with Left Shoulder Reconstruction: Outcomes at 24 Months
Authors: Lahlali Selma , Petruzzo Palmina , Gaillard Christophe , Kanitakis Jean , Huchon Laure , Feugier Patrick , Badet Lionel , Rode Gilles , Morelon Emmanuel , Gazarian Aram
Published: June 2024

Background:

Arm transplantation has been proposed as a valid therapeutic option for arm amputees. A bilateral arm transplantation including reconstruction of the left shoulder was performed on January 13, 2021 in Lyon (France).

Methods:

The recipient was a 48-year-old man with bilateral amputation at proximal arm level on both sides following an electric shock in 1998. He had received a liver transplant in 2002. The donor was a 35-year-old man. On the right side, the donor humerus was fixed on the remaining 9-cm-long proximal stump, and was reinforced with the donor fibula in an intramedullary fashion. On the left side, the whole donor humerus (including the humeral head) was transplanted with reconstruction of the gleno-humeral joint, including a suspension ligamentoplasty. The immunosuppressive protocol was based on antithymocyte globulins as induction therapy, and tacrolimus, steroids and mycophenolate mofetil as maintenance therapy.

Results:

Good bone healing and a well-positioned ligamentoplasty on the left side were achieved. At 2 years, the recipient was able to flex both elbows, and wrist extension, finger flexion, and extension were appreciated on both sides. Intrinsic muscle activity was detectable by electromyography during the eighth posttransplant month, and sensitivity was recovered. The patient is satisfied with his autonomy in some daily activities, but his greatest satisfaction is the recovery of his body image.

Conclusions:

These results confirm that it is possible to propose this transplantation to proximal-level arm amputees. The patients’ information about risks and limits as well as their compliance and determination remain important prerequisites.
Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement
Authors: Montano-Loza Aldo J. , Corpechot Christophe , Burra Patrizia , Schramm Christoph , Selzner Nazia , Ronca Vincenzo , Oo Ye H.
Published: June 2024

Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%–50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell–mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell–mediated rejection should be encouraged.
The economic impact of infection and/or nonunion on long-bone shaft fractures: a systematic review
Authors: Flores Michael J. , Brown Kelsey E. , O'Marr Jamieson M. , Adejuyigbe Babapelumi , Rodarte Patricia , Gomez-Alvarado Francisco , Nwachuku Kelechi , Urva Mayur , Shearer David
Published: June 2024

Background:

Long-bone fractures are a major cause of morbidity worldwide. These injuries are often complicated by infection or nonunion, which significantly affect patient quality of life and economic costs. Although studies have quantified the impact of these fractures, there is not a comprehensive review summarizing their economic and lifestyle costs.

Study Objective:

This review summarized the impact of long-bone fracture infection and nonunion on health-related quality of life, as measured by utility scores, and both direct and indirect economic costs.

Methods:

A systematic review was conducted using the following databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. The search included terms related to long-bone fractures, infection, nonunion, cost, and utility. The search yielded 1267 articles, and after deduplication, 1144 were screened, yielding 116 articles for full-text review. Screening was conducted using Covidence and extraction using REDCap.

Results:

Twenty-two articles met inclusion criteria, with the majority being from the United States and Europe. Most articles were retrospective studies, predominantly regarding the tibia. Fifteen articles contained cost data and 8 contained utility data, with 1 article containing both. Ten cost articles and 1 utility article contained infection data. 8 cost and all utility articles contained nonunion data. Infection ranged from 1.5 to 8.0 times the cost of an uncomplicated fracture. Nonunion ranged from 2.6 to 4.3 times the cost of an uncomplicated fracture. Utility data were variable and ranged from 0.62 to 0.66 for infection and 0.48–0.85 for nonunion.

Conclusions:

Infection and nonunion after long-bone fractures are associated with large decreases in health-related quality of life and incur substantial costs to both patients and health care systems. The data presented in this review quantify these impacts and may serve useful for future economic analyses. In addition, this study highlights the dearth of high-quality literature on this important topic.
A Multi-institutional Analysis of a Textbook Outcome Among Patients Undergoing Microvascular Breast Reconstruction
Authors: Shammas Ronnie L. , Hassan Abbas M. , Sergesketter Amanda R. , Berlin Nicholas L. , Mirza Humza N. , Guzman Natalie M. , Naga Hani I. , Vingan Perri , Govande Janhavi G. , Silverstein Max L. , Momeni Arash , Sisk Geoffroy C. , Largo Rene D. , Momoh Adeyiza O. , Nelson Jonas A. , Matros Evan , Phillips Brett T.
Published: June 2024

Background

Individual outcomes may not accurately reflect the quality of perioperative care. Textbook outcomes (TOs) are composite metrics that provide a comprehensive evaluation of hospital performance and surgical quality. This study aimed to investigate the prevalence and predictors of TOs in a multi-institutional cohort of patients who underwent breast reconstruction with deep inferior epigastric artery perforator flaps.

Methods

For autologous reconstruction, a TO was previously defined as a procedure without intraoperative complications, reoperation, infection requiring intravenous antibiotics, readmission, mortality, systemic complications, operative duration ≤12 hours for bilateral and ≤10 hours for unilateral/stacked reconstruction, and length of stay (LOS) ≤5 days. We investigated associations between patient-level factors and achieving a TO using multivariable regression analysis.

Results

Of 1000 patients, most (73.2%) met a TO. The most common reasons for deviation from a TO were reoperation (9.6%), prolonged operative time (9.5%), and prolonged LOS (9.2%). On univariate analysis, tobacco use, obesity, widowed/divorced marital status, and contralateral prophylactic mastectomy or bilateral reconstruction were associated with a lower likelihood of TOs (P < 0.05). After adjustment, bilateral prophylactic mastectomy (odds ratio [OR], 5.71; P = 0.029) and hormonal therapy (OR, 1.53; P = 0.050) were associated with a higher likelihood of TOs; higher body mass index (OR, 0.91; P = <0.001) was associated with a lower likelihood.

Conclusion

Approximately 30% of patients did not achieve a TO, and the likelihood of achieving a TO was influenced by patient and procedural factors. Future studies should investigate how this metric may be used to evaluate patient and hospital-level performance to improve the quality of care in reconstructive surgery.
The Fisher Subunit Anatomical Approach for Cleft Lip Revisions
Authors: Galarza Laura I. , Sudduth Jack D. , Rose Alexandra M. , Moss Clayton A. , Humphries Laura S. , Hoppe Ian C.
Published: June 2024

Many techniques exist to reapproximate a cleft lip but can leave unsatisfactory results with nonanatomic scars and a short upper lip, creating a need for revision. Many revisions focus on adjacent tissue transfers and realignment of landmarks, but in the senior authors' experience, recreating the defect and utilizing the Fisher repair for revision have led to aesthetically pleasing results and less noticeable scars. A database was collected that included all cleft lip revisions performed at a large, comprehensive children's hospital from October 2018 to July 2021. Inclusion criteria included any cleft patient with a cleft lip revision performed by two craniofacial surgeons. Data collected included sex, characteristics of the cleft lip, age at initial and index repair, type of initial repair, previous revisions, type of revision with any additional tissue rearrangement, and any nose repair. Sixty-five patients were included in the study for analysis. The type of initial repair was known in sixty-four cases (98%), and fifty-four were Millard repairs (83%). Twenty-two patients (33%) had a previous revision prior to their index revision. Sixty patients (92%) underwent the Fisher repair technique for their index revision and forty-six patients (70%) underwent nasal revision. In follow-up, all patients demonstrated an improvement in lip aesthetics. This study demonstrates a large subset of patients that have undergone cleft lip revision using the Fisher technique. In the senior surgeons' experience, the Fisher repair technique in the setting of cleft lip revision is an ideal way to address the shortcomings of historical repair techniques.
Targeted Muscle Reinnervation
Authors: Vonu Peter M. , Shekouhi Ramin , Crawford Kristina , Hones Keegan M. , Chim Harvey
Published: June 2024

Background

Targeted muscle reinnervation (TMR) has demonstrated efficacy in reducing neuroma and chronic pain. In this article, we investigated postoperative outcomes in our patient cohort, with a focus on the role of nonmodifiable factors such as patient age and gender.

Methods

Patients who had extremity TMR from April 2018 to October 2022 were reviewed. Outcomes of interest included patient age, gender, cause and type of amputation, delayed versus immediate TMR, as well as postoperative improvement in pain as assessed by numerical rating score (NRS).

Results

A total of 40 patients underwent TMR on 47 limbs. Mean age was 46.2 ± 17.0 years. Delayed TMR (27, 57.4%) was most commonly performed, followed by immediate and delayed-immediate at 11 (23.4%) and 9 (19.1%), respectively. Amputation level was most commonly above-knee in 20 (42.6%) patients, followed by below-knee (12, 25.5%), transhumeral (8, 17.0%), transradial (6, 12.8%), and shoulder (1, 2.1%). The median time interval between amputation and TMR was 12 months. The median preoperative NRS assessing residual limb pain (RLP) for patients who underwent delayed TMR was 10. The median postoperative NRS assessing RLP for all patients was 0 (interquartile range25–75: 0–5) and significantly improved compared with preoperative NRS (P< 0.001). At the last follow-up for limbs that had delayed and delayed-immediate TMR (n = 36), 33 (91.7%) limbs had more than 50% resolution of RLP. There was a significant difference in median postoperative NRS by gender (4 in men and 0 in women) (P< 0.05). Postoperative median NRS also favored younger patients (0, <50 years compared with 4.5, >50 years) (P< 0.05). Multiple linear regression analysis showed that, of different variables analyzed, only male gender and older age were predictive of poorer postoperative outcomes.

Conclusion

TMR showed high efficacy in our cohort, with improved short-term outcomes in women and younger patients.
Vasoactive and Antifibrotic Properties of Cannabinoids and Applications to Vasospastic/Vaso-Occlusive Disorders
Authors: Li Gabrielle , Choi Janice , Stephens Kristen L. , DeGeorge Brent R.
Published: June 2024

Background

Management of vasospastic and vaso-occlusive disorders is a complex challenge, with current treatments showing varied success. Cannabinoids have demonstrated both vasodilatory and antifibrotic properties, which present potential mechanisms for therapeutic relief. No existing review examines these effects in peripheral circulation in relation to vasospastic and vaso-occlusive disorders. This study aims to investigate vasodilatory and antifibrotic properties of cannabinoids in peripheral vasculature for application in vasospastic and vaso-occlusive disorders affecting the hand.

Methods

A systematic search was conducted by 2 independent reviewers across PubMed, Cochrane, Ovid MEDLINE, and CINAHL to identify studies in accordance with the determined inclusion/exclusion criteria. Information regarding study design, medication, dosage, and hemodynamic or antifibrotic effects were extracted. Descriptive statistics were used to summarize study findings as appropriate.

Results

A total of 584 articles were identified, and 32 were selected for inclusion. Studies were grouped by effect type: hemodynamic (n = 17, 53%) and antifibrotic (n = 15, 47%). Vasodilatory effects including reduced perfusion pressure, increased functional capillary density, inhibition of vessel contraction, and increased blood flow were reported in 82% of studies. Antifibrotic effects including reduced dermal thickening, reduced collagen synthesis, and reduced fibroblast migration were reported in 100% of studies.

Conclusion

Overall, cannabinoids were found to have vasodilatory and antifibrotic effects on peripheral circulation via both endothelium-dependent and independent mechanisms. Our review suggests the applicability of cannabis-based medicines for vasospastic and vaso-occlusive disorders affecting the hand (eg, Raynaud disease, Buerger disease). Future research should aim to assess the effectiveness of cannabis-based medicines for these conditions.
Methods of Evaluating EEG Reactivity in Adult Intensive Care Units: A Review
Authors: Hwang Jaeho , Cho Sung-Min , Geocadin Romergryko , Ritzl Eva K.
Published: June 2024

Purpose:

EEG reactivity (EEG-R) has become widely used in intensive care units for diagnosing and prognosticating patients with disorders of consciousness. Despite efforts toward standardization, including the establishment of terminology for critical care EEG in 2012, the processes of testing and interpreting EEG-R remain inconsistent.

Methods:

A review was conducted on PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted of articles published between January 2012, and November 2022, testing EEG-R on adult intensive care unit patients. Exclusion criteria included articles focused on highly specialized stimulation equipment or animal, basic science, or small case report studies. The Quality In Prognostic Studies tool was used to assess risk of bias.

Results:

One hundred and five articles were identified, with 26 variables collected for each. EEG-R testing varied greatly, including the number of stimuli (range: 1–8; 26 total described), stimulus length (range: 2–30 seconds), length between stimuli (range: 10 seconds–5 minutes), frequency of stimulus application (range: 1–9), frequency of EEG-R testing (range: 1–3 times daily), EEG electrodes (range: 4–64), personnel testing EEG-R (range: neurophysiologists to nonexperts), and sedation protocols (range: discontinuing all sedation to no attempt). EEG-R interpretation widely varied, including EEG-R definitions and grading scales, personnel interpreting EEG-R (range: EEG specialists to nonneurologists), use of quantitative methods, EEG filters, and time to detect EEG-R poststimulation (range: 1–30 seconds).

Conclusions:

This study demonstrates the persistent heterogeneity of testing and interpreting EEG-R over the past decade, and contributing components were identified. Further many institutional efforts must be made toward standardization, focusing on the reproducibility and unification of these methods, and detailed documentation in the published literature.
Reducing Blood Culture Contamination Rates: Introduction of a Combined Education and Skin Antisepsis Intervention
Authors: Mullane Niamh , O'Mara Niall , Coffey Darragh , Connolly Aine , O'Callaghan Isabelle , Kelly Deborah , Broderick Deirdre , Hickey Caitriona
Published: June 2024

Background
Blood culture contamination (BCC) is an important quality concern in clinical microbiology as it can lead to unnecessary antimicrobial therapy in patients and increased workload for laboratory scientists. The Clinical Laboratory and Standards Institute recommend BCC rates to be <3% and recently updated guidelines have set a new goal of 1%. The aim of this project was to design and implement interventions to reduce BCC rates at our institution.
Methods
We introduced a combined education and skin antisepsis intervention in a large Model 4 academic teaching hospital in the South of Ireland. BD ChloraPrep™ skin antisepsis applicators (2% chlorhexidine gluconate/70% isopropyl alcohol), licensed for use for blood culture collection, were introduced, replacing Clinell® (2% chlorhexidine gluconate/70% isopropyl alcohol) wipes. In addition, a multimodal education programme was designed and delivered. This consisted of a video demonstrating the recommended blood culture collection technique using the new applicators as well as simulation training for all interns. The video was uploaded to the intranet as an educational resource available to all staff.
Results
The interventions were implemented in July 2022 and BCC rates pre- and post-intervention were calculated. The average BCC rate for the 12 months preceding the intervention (July 2021-July 2022) was 2.56% with highest rates in the emergency department. This compared to an average rate of 2.2% in the 12 months post-intervention (July 2022-July 2023). In comparing the two rates the reduction in BCC rates between the two periods was not statistically significant (p=0.30).
Conclusion
Overall BCC rates reduced but the difference between the two periods did not reach statistical significance. The resource intensive nature of providing regular and timely feedback of contamination rates and the larger impact of in–person education and training over virtual modalities may explain the modest reduction. Further investments in these areas, particularly in the emergency department will be necessary to further reduce rates in line with new recommendations.
Cytoprotective and Neuroinductive Effects of Thiol-Containing Simple Signaling Molecules
Authors: Dahlgren Kylie J. , Hemmerla August J. , Moore Marissa A. , Calle Daniela , Ulery Bret D.
Published: June 2024

Around 20 million Americans, mostly young adults, have suffered from a peripheral nerve injury due to trauma or a medical condition. However, prevailing treatments, including those that employ exogenous growth factors, often exhibit drawbacks outweighing their benefits, highlighting the need for novel solutions. Non-complex agents that govern bioactivity, termed simple signaling molecules (SSMs), offer an exciting alternative when compared to traditional approaches due to their small size, ready availability, and influence on cellular pathways. This study explores the cytoprotective and neuroinductive effects of three thiol-containing SSMs: hydrogen sulfide (H2S), n-acetyl cysteine (NAC), and glutathione (GSH). Neural stem cells (NE-4Cs) were exposed to toxic levels of hydrogen peroxide (H2O2) while supplemented with different concentrations of H2S, NAC, or GSH to assess their cytoprotective effects. To study the neuroinductivity of H2S, NAC, and GSH with NE-4Cs, immunofluorescence microscopy for an early neuronal marker, β3-tubulin, was employed to determine stem cell neural differentiation. Significant cytoprotection was found for NAC (2 - 8 mM) and GSH (2 - 12 mM), while H2S showed limited protective effects. Interestingly, the opposite result was observed for neuroinductivity as only H2S (7.75 - 125 μM) achieved a desirable effect while NAC and GSH had minimal impact on neural differentiation. This research establishes therapeutic concentration ranges of H2S, NAC, and GSH for future drug delivery systems targeting neural regeneration, especially for peripheral nerve injuries.

LAY SUMMARY

Approximately 20 million Americans, mainly young adults, suffer from peripheral nerve injuries, necessitating new effective treatments. Currently emerging approaches, including growth factor-based therapies, unfortunately face considerable limitations. This study explores the potential of simple signaling molecules (SSMs) - small, readily available agents - specifically hydrogen sulfide (H2S), n-acetyl cysteine (NAC), and glutathione (GSH) for their potential to be used to address issues underlying peripheral nerve injuries. Our findings reveal NAC and GSH have cytoprotective effects, whereas H2S is neuroinductive. This research identifies optimal concentrations for future drug delivery targeting neural regeneration, especially beneficial for peripheral nerve injuries.

FUTURE WORKS

Upcoming investigation will concentrate on exploiting the potential of novel SSM-releasing monomers within degradable polymeric systems. This involves defining therapeutic windows and optimizing polymer chemistry to induce desired cytoprotective and neuroinductive effects in neural stem cells, crucial for peripheral nerve injury repair. Emphasizing controlled release, this approach holds promise for developing advanced therapeutic strategies utilizing H2S, NAC, and/or GSH in nerve guidance conduits.

GRAPHICAL ABSTRACT
Effect of cyclic loading on the ultimate tensile strength of small metallic suture anchors used for attaching artificial tendons in rabbits
Authors: Fidelis Obinna P. , Mulon Pierre-Yves , Anderson David E. , Crouch Dustin L.
Published: June 2024

Background

Suture anchor failures can lead to revision surgeries which are costly and burdensome for patients. The durability of musculoskeletal reconstructions is therefore partly affected by the design of the suture anchors.

Purpose

The purpose of the study was to quantify the strength of different suture anchors whose sizes are suitable for attaching artificial Achilles and tibialis cranialis tendons in a rabbit model, as well as determine the effect of cyclic loading on the anchoring strength.

Method

Four anchors (two with embedded eyelet and two with raised eyelet, n=5 per group) were tested with cyclical loading (1000 cycles and 4.5 mm/sec) and without cycling, to inform the failure loads and mode of failure of the suture anchors. An eyebolt screw with smooth eyelet was used as a control for the test groups.

Results

All samples in all groups completed 1000 cycles and failed via suture breakage in both test conditions. All anchors had failure loads exceeding the peak Achilles tendon force in rabbits during hopping gait. The data analysis showed an effect of anchor type on the maximum tensile force at failure (Fmax) in all suture categories but not an effect of loading condition. Also, the Anika anchor had a significantly less adverse effect on suture strength compared to Arthrex anchor (p=0.015), IMEX anchor (p=0.004) and Jorvet anchor (p<0.001). We observed a greater percentage of failure at the mid-section for the anchors with the raised eyelets compared to the anchors with embedded eyelets, which all failed at the knot.

Conclusion

Anchors with embedded eyelets had clinically preferred mode of failure with less adverse effects on suture and, may be more reliable than anchors with raised eyelets for attaching artificial Achilles and tibialis cranialis tendons in rabbits.