bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological studies likely need to consider PM2.5 composition even if total outdoor PM2.5 mass concentration is the exposure of interest
Authors: Weichenthal Scott , Christidis Tanya , Olaniyan Toyib , van Donkelaar Aaron , Martin Randall , Tjepkema Michael , Burnett Rick T. , Brauer Michael
Published: July 2024

Background:

Outdoor fine particulate air pollution, <2.5 µm (PM2.5) mass concentrations can be constructed through many different combinations of chemical components that have varying levels of toxicity. This poses a challenge for studies interested in estimating the health effects of total outdoor PM2.5 (i.e., how much PM2.5 mass is present in the air regardless of composition) because we must consider possible confounders of the version of treatment-outcome relationships.

Methods:

We evaluated the extent of possible bias in mortality hazard ratios for total outdoor PM2.5 by examining models with and without adjustment for sulfate and nitrate in PM2.5 as examples of potential confounders of version of treatment-outcome relationships. Our study included approximately 3 million Canadians and Cox proportional hazard models were used to estimate hazard ratios for total outdoor PM2.5 adjusting for sulfate and/or nitrate and other relevant covariates.

Results:

Hazard ratios for total outdoor PM2.5 and nonaccidental, cardiovascular, and respiratory mortality were overestimated due to the confounding version of treatment-outcome relationships, and associations for lung cancer mortality were underestimated. Sulfate was most strongly associated with nonaccidental, cardiovascular, and respiratory mortality suggesting that regulations targeting this specific component of outdoor PM2.5 may have greater health benefits than interventions targeting total PM2.5.

Conclusions:

Studies interested in estimating the health impacts of total outdoor PM2.5 (i.e., how much PM2.5 mass is present in the air) need to consider potential confounders of the version of treatment-outcome relationships. Otherwise, health risk estimates for total PM2.5 will reflect some unknown combination of how much PM2.5 mass is present in the air and the kind of PM2.5 mass that is present.
New perspective on the treatment of rheumatic arthritis based on “strengthening body resistance (Fú Zhèng)” in the theory of co-inhibitory receptor-regulated T-cell immunity
Authors: Xu Yifei , Zhong Linda , Liang Qianqian , Xu Hao
Published: July 2024

Co-inhibitory receptors serve as crucial regulators of T-cell function, playing a pivotal role in modulating the delicate balance between immune tolerance and autoimmunity. Initially identified in autoimmune disease models, co-inhibitory receptors, including CTLA-4, PD-1, TIM-3, and TIGIT, were found to be integral to immune regulation. Their blockade or absence in these models resulted in the induction or exacerbation of autoimmune diseases. Additionally, scholars have observed that co-inhibitory receptors on lymphocytes hold the potential to influence the prognosis in the context of chronic inflammation. Consequently, the blocking of co-suppressor receptors has emerged as a novel therapeutic approach for inhibiting refractory inflammatory diseases, particularly rheumatoid arthritis. From the standpoint of traditional Chinese medicine (TCM), the treatment of rheumatoid arthritis based on the “strengthening body resistance (Fú Zhèng)” theory can be construed as the regulation of co-suppressor receptors to modulate the body’s immune function in combating chronic inflammation. This article provides a succinct overview of the role of co-suppressor receptors in anti-inflammatory processes and explores the research prospects of co-suppressor receptor intervention in the treatment of rheumatoid arthritis. The exploration integrates the “strengthening body resistance (Fú Zhèng)” theory with relevant Chinese medicine formulations.
Formulations of traditional Chinese medicine for the prevention and treatment of radiation-induced injury
Authors: Niu Hong , Tang Ziyan , Chi Qiang , Du Lina , Jin Yiguang
Published: July 2024

The likelihood of radiation-induced injury (RII) has increased. Currently, the chemical drugs used to prevent and control radiation damage have some drawbacks, such as high toxicity, which can also have other side effects on the body. However, many traditional Chinese medicine (TCM) monomers, single TCM, and compound TCM preparations have shown good therapeutic effects against radiation damage with increased safety and minimal adverse reactions. Therefore, new anti-RII TCMs must be explored and developed. This study reviewed the TCM preparations for the prevention and treatment of RII and their mechanisms of action to provide a better theoretical basis for research on the prevention and treatment of RII. TCM is an efficient, safe, and convenient strategy for the prevention and treatment of RII.
Outcomes of Donor Corneas of Different Thicknesses From Endothelial Keratoplasty in Deep Anterior Lamellar Keratoplasty for Keratoconus
Authors: Zhao Yinghan , Du Kaiyue , Peng Rongmei , Hong Jing
Published: July 2024

Purpose:

To evaluate the outcomes of divided residual donor corneas obtained from endothelial keratoplasty in keratoconus with deep anterior lamellar keratoplasty (DALK).

Methods:

In this retrospective, comparative, clinical study, 103 keratoconic eyes that underwent DALK were enrolled; 67 eyes received thin grafts from Descemet stripping automated endothelial keratoplasty, and 36 received thick grafts from Descemet membrane endothelial keratoplasty. Baseline and postoperative central corneal thickness (CCT), inferior corneal thickness, uncorrected distance visual acuity, corrected distance visual acuity, corneal astigmatism, mean keratometry, biomechanical properties, and complication rates were measured.

Results:

Six months after transplantation, the group receiving thin grafts had a CCT of only 455.1 ± 43.0 μm, whereas that of the group receiving thick grafts was 546.7 ± 44.2 μm. Both CCT and inferior corneal thickness in the thin group were significantly lower than those in the thick group (measured with Pentacam at 36 months, P < 0.001) and remained throughout the 5-year follow-up period. Both procedures had comparable postoperative logarithm of the minimum angle of resolution UDVAs, logarithm of the minimum angle of resolution corrected distance visual acuity, astigmatism, and mean keratometry values (36 months; P = 0.335, 0.286, 0.680, and 0.365, respectively). Corneal biomechanical analysis revealed that the thin group had a significantly higher stiffness parameter at the first applanation than the thick group at the 2-year follow-up (P = 0.036) while other parameters were equivalent.

Conclusions:

The outcomes of keratoplasty with donor tissue are comparable regardless of the thickness of the graft, which suggests that transplantation with either type of the split corneal procedure for DALK in patients with keratoconus is feasible.
Peri-levator Betamethasone Versus Triamcinolone Injection in Management of Thyroid Eye Disease–related Upper Eyelid Retraction Without Proptosis
Authors: Awad Rawda A. , Abo-Ghadir Ahmed A. , Hussien Mohamed Shehata , Awad Ahmad A. , Kedwany Salma M. , Mohammad Abd El-Nasser A.
Published: July 2024

Purpose:

To compare the efficacy of peri-levator injection of both betamethasone and triamcinolone in the management of thyroid eye disease-related upper eyelid retraction without proptosis.

Methods:

This prospective, double-blind, randomized clinical trial was conducted at Assiut University Hospital, Upper Egypt in the period between December 2021 and October 2023. The study included 47 patients (56 eyes) and was divided into 2 groups. In group A, 1 ml betamethasone was injected into the peri-levator area, while in group B, 1 ml triamcinolone was injected. The injection was repeated every month for up to 5 injections if there was an improvement in margin reflex distance 1 (MRD1). The injection was stopped if MRD1 reached the normal value or if 2 successive injections caused no improvement in MRD1. The postinjection outcome was divided into: 1) effective if MRD1 reached the normal ≤4.5 mm; 2) partially effective if MRD1 was improved but did not reach the normal; and 3) ineffective if there was no improvement in MRD1. The follow up ranged from 6 to 20 months.

Results:

In group A, the injection was effective in 26 eyes (92.9%) and partially effective in 2 eyes (7.1%). In group B, the injection was effective in 17 eyes (60.7%), partially effective in 6 eyes (21.4%), and ineffective in 5 eyes (17.9%). The mean number of injections was significantly lower in group A than in group B: 1.61 ± 0.50 versus 2.36 ± 1.16.

Conclusions:

This study results suggest that betamethasone is more effective with a smaller number of injections than triamcinolone in the management of thyroid eye disease-related upper eyelid retraction.
Persons with Unilateral Transtibial Amputations Modulate Ipsilateral Hip and Contralateral Ankle Joint Work to Accelerate and Decelerate Walking
Authors: Chen Ethan , Shafer Anna , Stack Amanda , Pinhey Shay , Gordon Keith E.
Published: July 2024

Introduction

Loss of power production at the ankle joint contributes to many problems people with unilateral transtibial (UTT) amputation experience during walking. Little is known about walking acceleration and deceleration, which is common in daily living and may require substantial compensatory behaviors from the residual lower-limb joints.

Objective

The aim of this study was to quantify individual lower-limb joint contributions to walking acceleration and deceleration in people with UTT amputations. We hypothesized that joint work on the prosthetic limb would be primarily modulated at the hip, and joint work on the sound limb would be primarily modulated at the ankle.

Study Design

The study is a repeated-measures design.

Methods

Six K3 level ambulators with UTT amputations participated. Participants performed a total of 40 walking trials while wearing their own nonarticulated dynamic prosthetic foot and socket. Each trial consisted of walking along a straight walkway. After walking approximately 2 m, participants received a cue instructing them to perform one of three walking conditions: continue walking at a constant average velocity, rapidly accelerate, or rapidly decelerate. We used ground reaction forces and motion capture data to derive joint kinematics and kinetics during the three walking conditions. We used one-way repeated-measures analyses of variance (ANOVAs) to identify significant differences between conditions.

Results

For the sound limb, positive hip and ankle work was significantly greater during acceleration compared with constant average velocity or deceleration conditions, and negative knee work was significantly greater during acceleration compared with deceleration. For the prosthetic limb, negative ankle work was significantly greater during acceleration compared with deceleration.

Conclusions

People with UTT amputation who use nonarticulated prostheses primarily modulated joint work on their sound limb to accelerate or decelerate walking speed.

Clinical Relevance

Characterizing compensatory behaviors of people with a UTT amputation is important for understanding injury mechanisms, informing clinical guidelines, and improving future ankle-foot prosthesis designs.
Treatment-induced anogenital melanosis is a very frequent finding in patients with vulvar lichen sclerosus
Authors: Gambichler Thilo , Erdogan Gülgün , Weyer-Fahlbusch Sera S. , Susok Laura
Published: July 2024

Background:

Pigmented lesions such as melanosis have rarely been reported in patients with vulvar lichen sclerosus (VLS) that is typically characterized by hypopigmented lesions.

Objective:

We aimed to analyze systematically anogenital melanosis in a large cohort of VLS patients.

Methods:

We analyzed the clinical data of 198 female patients with VLS. The anogenital lesions of all patients were professionally photographed in a standardized position and illumination. Severity classification of architectural findings followed an easy-to-use clinical score. A modified Melasma Area and Severity Index and an image analysis software were used to evaluate the area and intensity of pigmentation.

Results:

According to the clinical score, 79 (198/39.9%) patients showed grade 1 disease, 78 (198/39.4%) grade 2, 37 (198/18.7%) grade 3, and 4 (198/2%) grade 4 disease. About 111 (56.1%) of the 198 patients had anogenital melanosis with a median modified Melasma Area and Severity Index of 3.6 (0.4–14). Univariate analysis revealed that anogenital melanosis was positively correlated with the use of topical estrogens (P = .0018) and negatively correlated with the use of pulsed high-dose corticosteroids plus low-dose methotrexate (PHDC-LDM, P = .021). On multivariable analysis, the use of topical hormone therapy turned out to be a strong independent predictor for the presence of anogenital melanosis (odds ratio: 4.57, 95% confidence interval: 1.66–12.57, P = .0033), whereas PHDC-LDM use was an independent predictor for the absence of anogenital melanosis (odds ratio: 0.35, 95% confidence interval: 0.15–0.84, P = .018).

Limitations:

The study includes the retrospective monocentric design.

Conclusion:

Anogenital melanosis is a very frequent and so far, under-reported clinical finding in VLS patients. It is likely caused by the use of topical estrogens employed for VLS treatment. In contrast, patients with more severe disease and PHDC-LDM treatment appear to develop less likely anogenital melanosis.
Expression of TGFβ-1 and CTGF in the Implanted Cochlea and its Implication on New Tissue Formation
Authors: Xiao Adam Y. , Lopez Ivan A. , Ishiyama Gail , Ishiyama Akira
Published: July 2024

Hypothesis

Transforming growth factor beta-1 (TGFβ-1) and connective tissue growth factor (CTGF) are upregulated in the implanted human cochlea.

Background

Cochlear implantation can lead to insertion trauma and intracochlear new tissue formation, which can detrimentally affect implant performance. TGFβ-1 and CTGF are profibrotic proteins implicated in various pathologic conditions, but little is known about their role in the cochlea. The present study aimed to characterize the expression of these proteins in the human implanted cochlea.

Methods

Archival human temporal bones (HTB) acquired from 12 patients with previous CI and histopathological evidence of new tissue formation as well as surgical samples of human intracochlear scar tissue surrounding the explanted CI were used in this study. Histopathologic analysis of fibrosis and osteoneogenesis was conducted using H&E. Protein expression was characterized using immunofluorescence. RNA expression from surgical specimens of fibrotic tissue surrounding the CI was quantified using qRT-PCR.

Results

TGFβ-1 and CTGF protein expressions were upregulated in the areas of fibrosis and osteoneogenesis surrounding the CI HTB. Similarly, surgical samples demonstrated upregulation of protein and mRNA expression of TGFβ-1 and mild upregulation of CTGF compared with control. TGFβ-1 was expressed diffusely within the fibrous capsule, whereas CTGF was expressed in the thickened portion toward the modiolus and the fibrosis-osteoneogensis junction.

Conclusion

To our knowledge, this is the first study to demonstrate increased expression of TGFβ-1 and CTGF in the human implanted cochlea and may provide better understanding of the mechanism behind this pathogenic process to better develop future mitigating interventions.
Tissue Classification After Bone-Anchored Hearing Implant Surgery: A Machine Learning Approach to Monitoring Skin Response
Authors: Cummine Jacqueline , Ostevik Amberley , Song Qi , Kim Yongbin , Nayar Suresh , Hodgetts William
Published: July 2024

Hypothesis

Here, we aim to 1) expand the available evidence for the use of machine learning techniques for soft tissue classification after BCD surgery and 2) discuss the implications of such approaches toward the development of classification applications to aid in tissue monitoring.

Background

The application of machine learning techniques in the soft tissue literature has become a large field of study. One of the most commonly reported outcomes after percutaneous bone-conduction device (BCD) surgery is soft tissue health. Unfortunately, the classification of tissue around the abutment as healthy versus not healthy is a subjective process, even though such decisions can have implications for treatment (i.e., topical steroid versus surgical revision) and resources (e.g., clinician time).

Methods

We built and tested a convolutional neural network (CNN) model for the classification of tissues that were rated as “green” (i.e., healthy), “yellow” (i.e., unhealthy minor), and “red” (i.e., unhealthy severe).

Methods

Representative image samples were gathered from a regional bone-conduction amplification site (N = 398; 181 samples of green; 144 samples of yellow; 73 samples of red). The image samples were cropped, zoomed, and normalized. Feature extraction was then implemented and used as the input to train an advanced CNN model.

Results

Accuracy of image classification for the healthy (“green”) versus not healthy (“yellow” and “red”) model was approximately 87%. Accuracy of image classification for the unhealthy (“yellow”) versus unhealthy (“red”) model was approximately 94%.

Conclusions

Monitoring tissue health is an ongoing challenge for BCD users and their clinicians not trained in soft tissue management (e.g., audiologists). If machine learning can aid in the classification of tissue health, this would have significant implications for stakeholders. Here we discuss how machine learning can be applied to tissue classification as a potential technological aid in the coming years.
Effect of hemolysis on D-dimer testing measured with the Improgen kit: is all manufacturer information correct?
Authors: Odabasi Merve Sena
Published: July 2024

D-dimer is a fibrin degradation product and its measurement is affected by hemolysis. This study was designed to reveal the value of hemolysis affecting D-dimer in our laboratory.

In this study, hemolysate samples obtained by both mechanical and freezing methods were used. D-dimer levels of all plasmas were measured with Improgen Diagnostic kit by immune-turbidimetric method. Numerical change in hemolyzed samples was evaluated by calculating the percentage difference, and clinically significant differences were evaluated by calculating the maximum acceptable bias (MAB).

In the hemolysate study prepared by both freeze-thaw and mechanical methods, it was observed that low D-dimer levels did not exceed the total allowable error (TAE) (30%) up to +2 hemolysis (corresponds to hemoglobin = 1.01–2 g/l) and did not exceed the MAB (65%) even at +4 hemolysis (corresponds to hemoglobin = 1.01–2 g/l). High D-dimer levels did not exceed the limit values of both TAE (30%) and MAB (68%) even in +4 hemolysis. The D-dimer test was affected by lower levels of hemolysis compared to both other studies and the values in the kit insert (hemoglobin >5 g/l corresponds to +4 hemolysis index).

We verified the hemolysis interference in the D-dimer test, which we thought was not compatible with the kit insert, under our own laboratory conditions. This is the first hemolysis interference study performed with the Improgen brand d-dimer kit. In samples with a hemolysis rate of +2 and above, it would be more accurate to reject the D-dimer result as a ‘hemolyzed sample’.
Geriatric nutritional risk index and quality of life among elderly hemodialysis patients: a cross-sectional study
Authors: Nouri Ali , Mansour-ghanaei Roya , Esmaeilpour-Bandboni Mohammad , Gholami Chaboki Bahare
Published: July 2024

Background:

Nutritional problems are considered one of the main complications of hemodialysis, and the geriatric nutritional risk index (GNRI) is a new instrument for assessing geriatric nutritional status. The present study sought to evaluate the relationship between the GNRI and quality of life (QOL) among elderly hemodialysis patients.

Methods:

In the present analytical cross-sectional study, 110 hemodialysis individuals were selected by applying a simple random sampling method, among whom 57 and 53 were males and females, respectively (mean: 70.3±6.93 years). Demographic characteristics, GNRI, and QOL status were determined. The data were analyzed using SPSS 20 software and descriptive statistics, Pearson’s correlation, ANOVA, independent sample t-tests, and multiple linear regression analysis.

Results:

The mean GNRI and mean total QOL were respectively obtained 93.903±11.067 and 20.95 ± 4.89. Among females, a significant direct relationship was observed between GNRI and total QOL (P = 0.010, r = 0.352), autonomy (P = 0.004, r = 0.389), and pleasure (P = 0.015, r = 0.333), while GNRI was not directly and significantly related to QOL in males (P = 0.161, r = 0.188).

Conclusion:

Due to the presence of a significant association between Geriatric GNRI and QOL among elderly hemodialysis patients, particularly among females, highlighting the importance of addressing nutritional status in optimizing well-being.
Incidental diagnosis of bilateral common iliac artery aneurysms: a case report and comprehensive literature review
Authors: katwal Shailendra , Katwal Srijana , Bhandari Sushmita , Paudel Pratiksha , Bhandari Devendra , Bhandari Shristi , Maharjan Santosh
Published: July 2024

Introduction and importance:

Aneurysms are dilatations of arteries, with abdominal aortic ectasias (AAE) considered precursors to abdominal aortic aneurysms (AAA). Iliac artery aneurysms (IAAs), often accompanying AAA, present a serious risk, particularly due to rupture. Here, the authors present a case highlighting the importance of recognizing and managing isolated bilateral common iliac artery aneurysms (CIAAs).

Case presentation:

A 66-year-old male presented following a road traffic accident (RTA) with ankle and leg pain. Examination revealed tenderness in the leg, mild right flank tenderness, and a history of mild pelvic pain. Biochemical studies showed deranged glucose and lipid levels. Imaging revealed large CIAAs, prompting surgical intervention. The patient’s fracture was also managed accordingly.

Clinical discussion:

CIAAs are rare but serious, typically occurring in elderly males with risk factors including advanced age, male sex, smoking, and hypertension, while diabetes and hyperlipidemia may exert protective effects. While often asymptomatic, they can lead to complications such as thrombosis or rupture. Diagnosis relies on imaging, and intervention is recommended for larger or symptomatic aneurysms.

Conclusion:

It’s crucial to consider CIAAs in high-risk individuals and recognize the significance of early detection and intervention to prevent potentially life-threatening complications. Prompt management, either through open surgical repair or endovascular options, is crucial for improving patient outcomes.
Evaluation of occlusal force changes in orthognathic surgery using force-sensing sensors in 3 years of follow-up
Authors: Duarte Fernando , Silva João Neves , Ramos Carina , Hopper Colin
Published: July 2024

Purpose:

The aim of this study was to test a prototype device called occlusal force diagnostic system in relation to occlusal force adaptation following orthognathic surgery.

Methods:

Retrospective study of 10 patients scheduled for a bimaxillary osteotomy involving a combination of maxillary Le Fort I impaction procedure coupled with a sagittal split advancement of the mandible; in a 3 years follow-up period.

Results:

The selection of examiner is not a variable that affects the occlusal force (N) measured by FSS sensors in any of the experimental conditions tested. The sensor position and the surgery recovery time affect the occlusal force irrespective of the examiner selection and/or the surgery recovery time.

Conclusion:

The piezoelectric sensors used in the present study have shown high reliability and validity of measurement. The surgery recovery time impacts the occlusal force (N), with a 50% increase in occlusal force (N) measured after 6 months post-surgery, with the value keeping stable at 36 months. This suggests that the patient is only fully recovered from the functional point-of-view at 6 months, having from that point on an improved and stable masticatory function.
Penetrating brain injury through the cavernous sinus by chopsticks in Vienamese: a case report
Authors: Dong He Van , Nguyen Anh Quoc , Dong Hanh Hong Thi , Vu Hai Trung , Pham Anh Hoang
Published: July 2024

Introduction and importance:

Penetrating brain injuries from chopsticks are exceedingly rare, often documented through case reports. Management strategies are tailored to individual cases, with a focus on mitigating postoperative complications.

Case presentation:

A 33-year-old male presented with a chopstick lodged in his right eye. Computed tomography (CT) imaging revealed two foreign bodies, prompting collaborative surgical removal by neurosurgery and ophthalmology teams. The procedure involved intricate bone drilling to access critical structures, ensuring a successful outcome with stability at 1-month follow-up.

Clinical discussion:

Common trajectories involve orbital roof penetration, posing risks of frontal lobe injury and intracerebral hematoma. Challenges arise with wooden foreign bodies, necessitating advanced imaging like CT angiography to assess vascular involvement. Surgical intervention offers benefits such as foreign body extraction, neurovascular protection, tissue debridement, hematoma evacuation, and dural repair.

Conclusion:

Although rare, chopstick-related penetrating brain injuries warrant vigilance in neurosurgical practice. Surgical intervention remains the cornerstone of treatment, ensuring optimal patient outcomes.
Elevated 68Ga-FAPI Activity in Benign Carotid Body Tumors
Authors: Xie Yang , Tang Wenxin , Chen Xi , Bai Xue , Chen Yue
Published: July 2024

We present 68Ga-FAPI PET/CT findings of benign carotid body tumor in a 33-year-old woman. Benign carotid body tumor demonstrated intense tracer uptakes on 68Ga-FAPI PET/CT. Our case suggests that benign carotid body tumors should be considered in the differential diagnosis of neck mass with elevated 68Ga-FAPI activity.
Levator Labii Superioris Alaeque Nasi Targeted Botulinum Toxin Injection for Treatment of Perinasal Facial Discomfort and Snarling
Authors: McClain Megan W. , Varman Archana , Varman Rahul
Published: July 2024

Botulinum toxin has been increasingly studied and used for varying conditions, most notably, cosmetics. However, it has been shown that botulinum toxin demonstrates a high efficacy in treating spasticity disorders throughout the body, including the face. Facial spasms vary in pathophysiology, region, and severity. Some can be so severe that they can cause discomfort and emotional distress due to the involuntary facial expressions caused by the spasms. Most spasticity conditions are often treated with adjuvant therapy of oral muscle relaxants and analgesics depending on severity. However, these treatments impose risks of varying adverse effects from sedation, hypotension, and if chronic use, more severe effects such as central nervous system complications or QT prolongation. In addition, if spasms are localized, the muscle relaxant’s mechanism is not targeted, leading to unnecessary systemic use. That being said, a more targeted and manageable treatment such as botulinum toxin presents itself as a potential option for patient’s physical condition and everyday life quality. Our case presents a 62-year-old male, with a chronic history of localized, idiopathic spasms and discomfort within the Levator Labii Superioris Aqulae Nasi region. The patient had no history of previous neurological disorders, and imaging was unremarkable. The patient had been treated over the past 13 years with varying oral therapeutics including Cymbalta, Ibuprofen, and cyclobenzaprine with limited improvement, but presented to the clinic seeking a different treatment plan, as the adverse effects from the muscle relaxants were impeding his everyday activities. The patient was also experiencing significant pain and emotional stress due to the spasms. The risk and benefits of treatment options were discussed and the patient decided to move forward with botulinum injections. After the first injection, the patient reported his pain had significantly improved and was relieved to be off of chronic pain medications. Our case demonstrates, what increasing literature further also supports: botulinum toxin is becoming a potential effective treatment for a breadth of spasticity disorders with a more targeted mechanism, and more manageable treatment plan, while simultaneously improving the patient’s quality of life.
RENIN AND ANGIOTENSIN (1–7) OFFER PREDICTIVE VALUE IN PEDIATRIC SEPSIS: FINDINGS FROM PROSPECTIVE OBSERVATIONAL COHORTS
Authors: Pi Dandan , Zheng Lijun , Gao Caixia , Xiao Changxue , Yu Zhicai , Fu Yueqiang , Li Jing , Chen Chengzhi , Liu Chengjun , Zou Zhen , Xu Feng
Published: July 2024

Background: Pediatric sepsis is a common and complex syndrome characterized by a dysregulated immune response to infection. Aberrations in the renin-angiotensin system (RAS) are factors in several infections of adults. However, the precise impact of RAS dysregulation in pediatric sepsis remains unclear. Methods: Serum samples were collected from a derivation cohort (58 patients with sepsis, 14 critically ill control subjects, and 37 healthy controls) and validation cohort (50 patients with sepsis, 37 critically ill control subjects, and 46 healthy controls). Serum RAS levels on day of pediatric intensive care unit admission were determined and compared with survival status and organ dysfunction. Results: In the derivation cohort, the serum renin concentration was significantly higher in patients with sepsis (3,678 ± 4,746) than that in healthy controls (635.6 ± 199.8) (P < 0.0001). Meanwhile, the serum angiotensin (1–7) was significantly lower in patients with sepsis (89.7 ± 59.7) compared to that in healthy controls (131.4 ± 66.4) (P < 0.01). These trends were confirmed in a validation cohort. Nonsurvivors had higher levels of renin (8,207 ± 7,903) compared to survivors (2,433 ± 3,193) (P = 0.0001) and lower levels of angiotensin (1–7) (60.9 ± 51.1) compared to survivors (104.0 ± 85.1) (P < 0.05). A combination of renin, angiotensin (1–7) and procalcitonin achieved a model for diagnosis with an area under the receiver operating curve of 0.87 (95% CI: 0.81–0.92). Conclusion: Circulating renin and angiotensin (1–7) have predictive value in pediatric sepsis.
MICROBIOME AND INFLAMMASOME ALTERATIONS FOUND DURING RADIATION DOSE FINDING IN A SINCLAIR MINIPIG MODEL OF GASTROINTESTINAL ACUTE RADIATION SYNDROME
Authors: Horseman Timothy S. , Parajuli Babita , Frank Andrew M. , Weaver Alia , Schauer David A. , Moran Sean , Anderson Joseph A. , Holmes-Hampton Gregory P. , Burmeister David M.
Published: July 2024

Both abdominal radiotherapy and a nuclear event can result in gastrointestinal symptoms, including acute radiation syndrome (GI-ARS). GI-ARS is characterized by compromised intestinal barrier integrity increasing the risk for infectious complications. Physiologically relevant animal models are crucial for elucidating host responses and therapeutic targets. We aimed to determine the radiation dose requirements for creating GI-ARS in the Sinclair minipig. Male, sexually mature swine were randomly divided into sham (n = 6) and three lower hemibody radiation dosage groups of 8, 10, and 12 Gy (n = 5/group) delivered using linear accelerator-derived x-rays (1.9 Gy/min). Animals were monitored for GI-ARS symptoms for 14 days with rectal swab and blood collection at days 0–3, 7, 10, and 14 followed by necropsy for western blotting and histology. Dose-dependent increases in weight loss, diarrhea severity, and mortality (log-rank test, P = 0.041) were seen. Villi length was significantly reduced in all irradiated animals compared to controls (P < 0.001). Serum citrulline decreased and bacterial translocation increased after irradiation compared to controls. Increased NLRP3 levels in post-mortem jejunum were seen (P = 0.0043) as well as increased IL-1β levels in the 12 Gy group (P = 0.041). Radiation dose and survival were associated with significant gut microbial community shifts in beta diversity. Moreover, decedents had increased Porphyromonas, Campylobacter, Bacteroides, Parvimonas, and decreased Fusobacterium and decreased Aerococcus, Lactobacillus, Prevotella, and Streptococcus. Our novel Sinclair minipig model showed dose-dependent clinical symptoms of GI-ARS. These findings provide invaluable insights into the intricate interplay between GI-ARS, intestinal inflammation, and gut microbiota alterations offering potential targets for therapeutic and diagnostic interventions after radiation exposure.
Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion
Authors: Hoffman Jordan R.H. , Hartwig Matthew G. , Cain Michael T. , Rove Jessica Y. , Siddique Aleem , Urban Marian , Mulligan Michael S. , Bush Errol L. , Balsara Keki , Demarest Caitlin T. , Silvestry Scott C. , Wilkey Barbara , Trahanas John M. , Pretorius Victor G. , Shah Ashish S. , Moazami Nader , Pomfret Elizabeth A. , Catarino Pedro A. ,   In collaboration with members from The American Society of Transplant Surgeons (ASTS), The International Society of Heart and Lung Transplantation (ISHLT), The Society of Thoracic Surgeons (STS), and The American Association for Thoracic Surgery (AATS)
Published: July 2024

Background.

Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique.

Methods.

A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions.

Results.

The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process.

Conclusions.

The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.
American Society of Transplant Surgeons Normothermic Regional Perfusion Standards: Ethical, Legal, and Operational Conformance
Authors: Wall Anji E. , Merani Shaheed , Batten Jason , Lonze Bonnie , Mekeel Kristin , Nurok Michael , Prinz Jennifer , Gil John , Pomfret Elizabeth A. , Guarrera James V.
Published: July 2024

Background.

The American Society of Transplant Surgeons convened a multidisciplinary working group to address operational, ethical, and legal considerations surrounding normothermic regional perfusion (NRP) procurement.

Methods.

The working group, comprising members from American Society of Transplant Surgeons and AST across various disciplines including transplant surgery, hepatology, critical care, and bioethics, collaborated to formulate recommendations and guidance for NRP procurement.

Results.

The following topics were identified by the group as essential standards that need to be addressed for ethical, legal, and operational conformance: terminology; conceptualization of death in the context of NRP; and communication, logistics, and training and competency.

Conclusions.

Fourteen recommendations that support the ethical and legal acceptability of NRP in the United States and set expectations for the conduct of NRP procedures are provided.
Sex and gender differences in cancer in individuals with severe mental disorders
Authors: Bajić Žarko , Vuk-Pisk Sandra , Filipčić Igor , Šimunović Filipčić Ivona
Published: July 2024

Purpose of review

Although cancer incidence is similar between individuals with severe mental disorders (SMD) and the general population (GP), survival rates are lower, particularly in those with schizophrenia. While the scientific and medical communities acknowledge sex differences in cancer mechanisms, including risk factors and cancer types, less is known about sex and gender disparities in incidence, mortality, and care pathways among those with SMD. This review aims to explore these differences in cancer among individuals with SMD.

Recent findings

Current evidence on sex and gender differences in cancer care for SMD is limited. It is unclear how these factors affect cancer incidence and mortality in the SMD population, and if they correspond to those in the GP. The literature frequently omits detailed information on sex-based differences in SMD-related cancer rates, complicating conclusive analysis. Moreover, people with SMD experience significant challenges in accessing cancer screenings compared to the GP, and findings on sex and gender disparities in this context remain inconclusive.

This review emphasizes that while significant sex and gender-based differences in cancer mechanisms, incidence, and survival exist within the GP, they have not been fully integrated into clinical practice. It underscores the need of addressing these differences in cancer incidence, outcomes, mortality, and care pathways to enhance treatment for individuals with SMD.
Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders
Authors: Schmidt A. Floriaan , Finan Chris , Chopade Sandesh , Ellmerich Stephan , Rossor Martin N. , Hingorani Aroon D. , Pepys Mark B.
Published: July 2024

The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral A
β
amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted
cis
-Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11,
p
= 1.8 × 10
−3
), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59,
p
= 1.5 × 10
−5
) and plasma tau concentration (0.06 log
2
(ng l
−1
) 95%CI 0.03; 0.08,
p
= 4.55 × 10
−6
). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.
Human EWS-FLI protein levels and neomorphic functions show a complex, function-specific dose–response relationship in
Drosophila
Authors: Mahnoor Serena , Molnar Cristina , Velázquez Diego , Reina Jose , Llamazares Salud , Heinen Jan Peter , Mora Jaume , Gonzalez Cayetano
Published: July 2024

Ewing sarcoma (EwS) is a cancer that arises in the bones and soft tissues, typically driven by the Ewing’s sarcoma breakpoint region 1-Friend leukemia virus integration 1 (EWS-FLI) oncogene. Implementation of genetically modified animal models of EwS has proved difficult largely owing to EWS-FLI’s high toxicity. The EWS-FLI
1FS
frameshift variant that circumvents toxicity but is still able to perform key oncogenic functions provided the first study model in
Drosophila
. However, the quest for
Drosophila
lines expressing full-length, unmodified EWS-FLI remained open. Here, we show that EWS-FLI
1FS
’s lower toxicity is owed to reduced protein levels caused by its frameshifted C-terminal peptide, and report new strategies through which we have generated
Drosophila
lines that express full-length, unmodified EWS-FLI. Using these lines, we have found that the upregulation of transcription from GGAA-microsatellites (GGAAμSats) presents a positive linear correlation within a wide range of EWS-FLI protein concentrations. In contrast, rather counterintuitively, GGAAμSats-independent transcriptomic dysregulation presents relatively minor differences across the same range, suggesting that GGAAμSat-dependent and -independent transcriptional upregulation present different kinetics of response with regards to changing EWS-FLI protein concentration. Our results underpin the functional relevance of varying EWS-FLI expression levels and provide experimental tools to investigate, in
Drosophila
, the effect of the EWS-FLI ‘high’ and ‘low’ states that have been reported and are suspected to be important for EwS in humans.
Attribution of undesirable character traits, rather than trait-based dehumanization, predicts punishment decisions
Authors: Brennan Robert A. , Enock Florence E. , Over Harriet
Published: July 2024

Previous work has reported that the extent to which participants dehumanized criminals by denying them uniquely human character traits such as refinement, rationality and morality predicted the severity of the punishment endorsed for them. We revisit this influential finding across six highly powered and pre-registered studies. First, we conceptually replicate the effect reported in previous work, demonstrating that our method is sensitive to detecting relationships between trait-based dehumanization and punishment should they occur. We then investigate whether the apparent relationship between trait-based dehumanization and punishment is driven by the desirability of the traits incorporated into the stimulus set, their perceived humanness, or both. To do this, we asked participants to rate the extent to which criminals possessed uniquely human traits that were either socially desirable (e.g. cultured and civilized) or socially undesirable (e.g. arrogant and bitter). Correlational and experimental evidence converge on the conclusion that apparent evidence for the relationship between trait-based dehumanization and punishment is better explained by the extent to which participants attribute socially desirable attributes to criminals rather than the extent to which they attribute uniquely human attributes. These studies cast doubt on the hypothesized causal relationship between trait-based dehumanization and harm, at least in this context.
A standardised approach to quantifying activity in domestic dogs
Authors: Karimjee Kamila , Harron Rachel C. M. , Piercy Richard J. , Daley Monica A.
Published: July 2024

Objective assessment of activity via accelerometry can provide valuable insights into dog health and welfare. Common activity metrics involve using acceleration cut-points to group data into intensity categories and reporting the time spent in each category. Lack of consistency and transparency in cut-point derivation makes it difficult to compare findings between studies. We present an alternative metric for use in dogs: the acceleration threshold (as a fraction of standard gravity, 1 g = 9.81 m/s
2
) above which the animal's X most active minutes are accumulated (MX
ACC
) over a 24-hour period. We report M2
ACC,
M30
ACC
and M60
ACC
data from a colony of healthy beagles (
n
= 6) aged 3–13 months. To ensure that reference values are applicable across a wider dog population, we incorporated labelled data from beagles and volunteer pet dogs (
n
= 16) of a variety of ages and breeds. The dogs' normal activity patterns were recorded at 200 Hz for 24 hours using collar-based Axivity-AX3 accelerometers. We calculated acceleration vector magnitude and MX
ACC
metrics. Using labelled data from both beagles and pet dogs, we characterize the range of acceleration outputs exhibited enabling meaningful interpretation of MX
ACC
. These metrics will help standardize measurement of canine activity and serve as outcome measures for veterinary and translational research.
Actions speak louder than words: the case for responsible scientific activism in an era of planetary emergency
Authors: Wyatt Tristram D. , Gardner Charlie J. , Thierry Aaron
Published: July 2024

The world's understanding of the climate and ecological crises rests on science. However, scientists' conventional methods of engagement, such as producing ever more data and findings, writing papers and giving advice to governments, have not been sufficiently effective at persuading politicians to act on the climate and ecological emergency. To date, governments’ decisions (such as continuing with vast subsidies for fossil fuels) clearly show that powerful vested interests have been much more influential than the amassed scientific knowledge and advice. We argue that in the face of this inaction, scientists can have the maximum amount of influence by lending their support to social movements pressing for action, joining as active participants and considering civil disobedience. Scientists seeking to halt continued environmental destruction also need to work through our institutions. Too many scientific organizations, from national academies of science to learned societies and universities, have not taken practical action on climate; for example, many still partner with fossil fuel and other compromised interests. We therefore also outline a vision for how scientists can reform our scientific institutions to become powerful agents for change.
Individual and team performance in cricket
Authors: Sadekar Onkar , Chowdhary Sandeep , Santhanam M. S. , Battiston Federico
Published: July 2024

Advancements in technology have recently allowed us to collect and analyse large-scale fine-grained data about human performance, drastically changing the way we approach sports. Here, we provide the first comprehensive analysis of individual and team performance in One-Day International cricket, one of the most popular sports in the world. We investigate temporal patterns of individual success by quantifying the location of the best performance of a player and find that they can happen at any time in their career, surrounded by a burst of comparable top performances. Our analysis shows that long-term performance can be predicted from early observations and that temporary exclusions of players from teams are often due to declining performances but are also associated with strong comebacks. By computing the duration of streaks of winning performances compared to random expectations, we demonstrate that teams win and lose matches consecutively. We define the contributions of specialists such as openers, all-rounders and wicket-keepers and show that a balanced performance from multiple individuals is required to ensure team success. Finally, we measure how transitioning to captaincy in the team improves the performance of batsmen, but not that of bowlers. Our work emphasizes how individual endeavours and team dynamics interconnect and influence collective outcomes in sports.