bluuebunny/crossref_metadata_2025 huggingface dataset:
Concussion Incidence, Mechanism, and Perspectives Among Australian Elite Surfers: Implications for Medical Support and Safety Protocols
Authors: Ward John , Haakonssen Eric , Parsonage Joanna
Published: September 2024

Objective:

The primary objective was to investigate the incidence of concussion and the associated mechanisms of injury in elite Australian surfers. The secondary objective was to investigate the current perspectives and behaviors related to experiencing concussion in surfing.

Design:

A cross-sectional, retrospective, descriptive survey.

Setting:

Surfing Australia high-performance program.

Participants:

Forty nationally identified elite Australian surfing athletes.

Intervention:

A retrospective survey collected information pertaining to participant demographics, concussion history, potential concussive symptoms, such as headache, neck pain, dizziness, or unusual fatigue, following a wipeout, and participants' perspectives on concussion.

Main Outcome Measures:

Investigating concussion incidence among elite Australian surfers compared with potential undiagnosed concussive episodes.

Results:

Surfers with a history of diagnosed surfing-related concussion (DC) were compared with those with no history of a diagnosed surfing-related concussion (NDC). A total of 13 of 40 surfers had a DC, with “contact versus the water surface” identified as the primary mechanism. Both DC and NDC groups had a high frequency of concussive symptoms after a surfing wipeout with a total of 447 and 573 concussive symptom occurrences reported in the DC and NDC groups, respectively. Concern regarding the long-term impacts of concussion were reported in 25 of 40 surfers.

Conclusions:

The number of concussive symptoms reported by surfers who had not previously been diagnosed with concussion suggests that concussion may be underreported and underdiagnosed in elite surfing. This underscores the need for increased medical support, education, and improved safety protocols.
Enhancing Heart Failure Care: Deep Learning-Based Activity Classification in Left Ventricular Assist Device Patients
Authors: Berger Laurenz , Haberbusch Max , Gross Christoph , Moscato Francesco
Published: September 2024

Accurate activity classification is essential for the advancement of closed-loop control for left ventricular assist devices (LVADs), as it provides necessary feedback to adapt device operation to the patient’s current state. Therefore, this study aims at using deep neural networks (DNNs) to precisely classify activity for these patients. Recordings from 13 LVAD patients were analyzed, including heart rate, LVAD flow, and accelerometer data, classifying activities into six states: active, inactive, lying, sitting, standing, and walking. Both binary and multiclass classifiers have been trained to distinguish between active and inactive states and to discriminate the remaining categories. The models were refined by testing several architectures, including recurrent and convolutional layers, optimized via hyperparameter search. Results demonstrate that integrating LVAD flow, heart rate, and accelerometer data leads to the highest accuracy in both binary and multiclass classification. The optimal architectures featured two and three bidirectional long short-term memory layers for binary and multiclass classifications, respectively, achieving accuracies of 91% and 84%. In this study, the potential of DNNs has been proven for providing a robust method for activity classification that is vital for the effective closed-loop control of medical devices in cardiac care.
Justifying access to kidney care in low resource and humanitarian settings
Authors: Sawhney Simon , Luyckx Valerie A.
Published: September 2024

Purpose of review

Access to and quality of kidney care is not equitable between or within countries. A natural question is whether global kidney care inequities are always unjustifiable and unfair, or are sometimes due to unavoidable competing or conflicting ethical duties or responsibilities.

Recent findings

Health is a fundamental right for all people. People with kidney conditions should have the same claim on this human right as others. Countries have an obligation to progressively fulfil this right and a duty to do so equitably, but global progress has been slow. Countries with limited resources or faced with humanitarian emergencies must set priorities to allocate resources fairly. This process involves trade-offs and often people requiring kidney replacement therapy are left out because of costs, logistics and lack of data. Major burdens are placed on clinicians who grapple between their duty to their patient and professional codes and their responsibility to a ‘greater good’. These dilemmas apply also to industry, governments and the international community who must recognize their share in these duties.

Inequities in kidney health and care must be acknowledged and sustainable and collaborative solutions urgently found such that right to kidney care is progressively upheld for everyone everywhere.
Three-dimensional evaluation of a giant torus in the maxilla and mandible that affected pronunciation: a case report
Authors: Sasaki Jun , Suzuki Kenta , Kashihara Sho , Saito Terumi
Published: September 2024

Introduction and importance:

Tori in the maxilla and mandible are often clinically asymptomatic, but can often lead to issues such as obstruction of denture attachment and dysarthria. The authors describe a case involving a substantial torus in the maxilla and mandible that significantly affected speech articulation.

Case presentation:

A 72-year-old woman presented with a pronounced torus in the maxilla and mandible. Surgical resection of the lesion resulted in improved tongue movement. Through both pre and postoperative assessments, the authors evaluated pronunciation, generated a three-dimensional (3D) computed tomography (CT)–based image, and quantified the extent of bone removal. A 6-month follow-up demonstrated no recurrence of the condition.

Clinical discussion:

Surgical intervention leads to improvements in soft palate sounds. The surgical intervention proved effective in ameliorating speech articulation difficulties, and the application of 3D-CT image construction was valuable.

Conclusion:

To summarize, the authors successfully managed and treated a giant torus in the maxilla and mandible, a condition scarcely been reported in the literature. This report is the first to detail the application of 3D analysis for the evaluation a torus.
Overuse of tetanus toxoid vaccine: a common but under-addressed issue in Nepal
Authors: Shrestha Suraj , Aryal Roshan , Yadav Randhir S. , Baidya Sujita , Acharya Suman , Bhandari Sanjeeb S.
Published: September 2024

Introduction and importance:

Tetanus, though potentially fatal, is preventable with proper vaccination, but high tetanus titers from frequent or higher doses can lead to increased adverse events. In countries like Nepal, where tetanus vaccines are readily available over the counter, irrational and frequent dosing, especially in certain occupational groups, is a noted issue.

Case presentation:

A 28-year-old metal worker presented with a superficial cut on his forearm, managed with standard wound care, and reported a history of frequent tetanus vaccinations. Given his extensive vaccination history, a tetanus toxoid injection was deemed unnecessary, and he was educated on proper vaccination schedules and advised to seek medical attention for future injuries.

Clinical discussion:

Timely administration of vaccines for pre-exposure and postexposure prophylaxis is crucial for combating tetanus, with booster doses recommended every 10 years or as needed for wound management. High antibody titers from frequent tetanus vaccinations can increase the risk of adverse events, prompting guidelines to avoid administering Td more frequently than every 10 years unless necessary. Local reactions, like pain and swelling at the injection site, are common, while systemic reactions can include fever and peripheral neuropathy. Over-immunization is a concern in some regions, with frequent unnecessary booster doses potentially causing harm and highlighting the need for adherence to vaccination guidelines.

Conclusion:

Modifying and monitoring adult Td booster vaccination can lead to significant cost savings and fewer adverse events, requiring proper vaccination record-keeping, accurate assessment, and adherence to guidelines by healthcare workers.
Exploring the effect of diet programs on the behavior of Sudanese children with autism and the prevalence and association of gastrointestinal symptoms: a multi-center cross-sectional study
Authors: Elawad Sara , Omer Mohamed Elawad Shaima , Elbadawi Mohamed H. , Yousif Abdalla Sosal Wafa , Mohamed Khalid Leena , Rabeie Hassan AbdEldaim Doaa , Hemmeda Lina , Abbasher Hussien Mohamed Ahmed Khabab , Mustafa Ahmed Ghassan E.
Published: September 2024

Background and aims:

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social difficulties, speech and nonverbal communication issues, and restricted behaviors. Nutritional issues, such as food allergies and intolerances, can affect children with ASD. This study aimed to evaluate the impact of diet programs on ASD behavior and gastrointestinal symptoms, which would be considered as a starting point to increase the family’s knowledge about how to practice healthy and suitable dieting for their children.

Materials and methods:

The study was a cross-sectional observational study on 45 children with an autism spectrum disorder in four centers aged 2–18 in Khartoum state. Data was collected through an interview questionnaire, which included sociodemographic, diet, gastrointestinal, and behavioral assessments. The data was analyzed using SPSS to find the correlation between the various variables. Independent t-test, Analysis of Variance, and Mann–Whitney test were used in univariant analysis to assess the association between study variables, while multiple linear regression was used in multivariant analysis for the same purpose

Results:

The study involved a large number of children with autism spectrum disorder (ASD), with 80% being male and 73.3% being school-aged. Most had parents as guardians and 71.1% were in intermediate financial status. About 20% were overweight or obese, and 57.8% did not have a specific diet program. Food selectivity was prevalent, with 22.7% having allergies to milk and wheat. ASD children experienced vomiting, gastric reflux, abdominal pain, and changes in stool characteristics. A significant link was found between financial status, behavioral status and gastrointestinal changes. High financial status was significantly different from intermediate and low statuses based on behavioral changes. However, no significant association was found in multivariant analysis.

Conclusion:

The study found that ASD children generally have good nutritional health, with a higher degree of dietary selection. The financial status of guardians significantly influenced behavioral and gastrointestinal changes in the children. Further interventional studies are recommended to assess the direct impact of diet programs on these symptoms.
Extra-skeletal Ewing sarcoma of the diaphragm in a young female: a case report
Authors: Imran Muhammad , Dar Habib Ahmad , Shahzad Faizan , Farhan Muhammad , Jielani Asif , Daudi Tajammul , Dave Tirth , Hina Sadia , Mamoon Nadira
Published: September 2024

Introduction and importance:

Extra-skeletal Ewing sarcoma (EES) belongs to the family of primitive neuroectodermal tumors (PNET) and arises from soft tissue, with only 30 cases reported in the literature until now. Early diagnosis is crucial, and the management requires a multidisciplinary approach for better patient outcomes and survival.

Case presentation:

A 20-year-old female presented to the surgical outpatient department with complaints of shortness of breath and right lower chest pain. Upon physical examination, a lipomatous lesion was observed. Ultrasound and CT scan showed a heterogeneously enhancing soft tissue mass in the right lower hemithorax causing erosion and osteolysis of the right 9th rib, involving intercostal muscles, and exerting mass effect on the underlying hemidiaphragm. Later USG-guided Tru-cut biopsy was performed to confirm the diagnosis, which reported Ewing sarcoma with CD 99, FL-1, and NKX 2.2 positive. En-bloc tumor resection along with a portion of the diaphragm was performed, and a tube thoracostomy was carried out. Chest wall reconstruction was done with mesh and a local muscle rotation flap cover. Adjuvant chemotherapy was initiated.

Clinical discussion:

EES often presents with vague symptoms such as shortness of breath or abdominal or chest pain, thus making the diagnosis even more difficult. However, it has a relatively poor prognosis and thus is an important differential to rule out.

Conclusion:

Extra-skeletal Ewing Sarcoma is a highly aggressive tumor that requires prompt diagnosis and treatment, with surgical resection being the first line of treatment. Adjuvant chemotherapy has also shown better outcomes.
Cost Evaluation of Subcutaneous Trastuzumab Versus Intravenous Trastuzumab for the Treatment of HER2-Positive Breast Cancer: Insights From Oncology Hospitals in Morocco
Authors: Ouasrhir Abdelali , Ouenzar Lamia , Zoughagh Btissam
Published: September 2024

Context:

Over the course of over 20 years, trastuzumab has been a keystone in the treatment of human epidermal growth factor receptor 2–positive breast cancer. Trastuzumab administered both intravenously and subcutaneously show consistent pharmacokinetic characteristics and have been shown to have similar levels of safety and effectiveness.

Objectives:

Our study's main objective was to perform a thorough comparison of the medical and pharmaceutical expenses related to the two different pharmaceutical formulations. We specifically want to evaluate the financial effects of treating individuals weighing between 60 and 73 kg with trastuzumab, which was initially administered subcutaneously, in 1,474 treatment cases. Our study includes a simulation analysis that takes into account multiple scenarios and accounts for both the cost of the medication and the related medical bills.

Results:

From a database containing 542 patients with cancer, the study collected 4,437 therapy cases in total divided into three categories: initial dose, loading dose, and maintenance dose. 65.1% of the patients weighed less than 69 kg. In 62.9% of instances, the hospital pharmacy provided subcutaneous trastuzumab. For patients with cancer weighing between 60 and 73 kg, the simulated scenarios included the computation of overall expenses (subcutaneous [SC]: 1,370,516.60 USD and intravenous [IV]: 941,178.42 USD) and possible budget savings if the therapies were administered in IV rather than SC, totaling 428,765.60 USD.

Conclusion:

Beyond just taking medication costs into account, our research may help to clarify the differences between pharmaceutical formulations intended for IV and SC administration. In reality, we recognize that other variables—like the patient's weight and the financial models used by oncology institutions and health care workers—may also be quite important.
STK11 Adnexal Tumor: Exploring the Association With Peutz-Jeghers Syndrome and its Distinction From Morphologic Mimickers
Authors: Bennett Jennifer A. , Oliva Esther
Published: September 2024

STK11 adnexal tumor is a novel malignant neoplasm of uncertain histogenesis frequently arising in a para-adnexal location and associated with Peutz-Jeghers syndrome in ∼50% of patients. Its broad morphologic spectrum and nonspecific immunohistochemical profile has resulted in misclassification in the past as a variety of other neoplasms including those of wolffian, sex cord-stromal, mesothelial, and epithelial derivation. This review focuses on the spectrum of adnexal neoplasms that may develop in Peutz-Jeghers syndrome, with particular emphasis on STK11 adnexal tumor and its differential diagnosis.
“Uterine-type” Extra-uterine High-grade Sarcoma of the Rectovaginal Septum: Case Report and Review of Literature
Authors: Khaled Chirine , D’Haene Nicky , Noël Jean-Christophe
Published: September 2024

The rectovaginal septum is an unusual location for neoplastic processes. The majority of these are extensions of tumors of the rectum or vagina. Masses arising primarily from the rectovaginal fascia are rare. Most primary rectovaginal malignant neoplasms are carcinomas that arise in the setting of endometriosis. Sarcomas in this location are exceedingly rare, with only few cases reported in the literature. We report a case of a 44-year-old lady who developed a high-grade sarcoma in the rectovaginal septum in the setting of endometriosis. We also discussed the differential diagnosis of this lady’s challenging and unique lesion, which is most probably an extra-uterine “uterine-type” high-grade sarcoma that shows overlapping features of several entities. Moreover, we performed a literature review of sarcomas in this rare location. Given the fact that the rectovaginal septum is a common location for endometriosis, in the case of a rectovaginal neoplasm, a thorough sampling and a careful search for endometriotic lesions are important, as they may be a clue for the diagnosis. Although rare, sarcomas should always be considered in the differential diagnosis of rectovaginal neoplasms.
Whole-exome Sequence Analysis of Gastric-type Adenocarcinoma of the Uterine Cervix and Adjacent Lobular Endocervical Glandular Hyperplasia in the Same Case
Authors: Miyamoto Tsutomu , Ida Koichi , Tanaka Yasuhiro , Asaka Shiho , Shiozawa Tanri
Published: September 2024

Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS, indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS’s pathogenesis and biological characteristics.
Updated National and State-Specific Prevalence of Congenital Cytomegalovirus Infection, United States, 2018-2022
Authors: Lutz Chelsea S. , Schleiss Mark R. , Fowler Karen B. , Lanzieri Tatiana M.
Published: September 2024

Context:

Congenital cytomegalovirus (cCMV) infection is the most common infectious cause of birth defects and the leading non-genetic cause of sensorineural hearing loss in the United States. Prior national cCMV infection prevalence estimates were based on one multi-site screening study conducted between 2007 and 2012 and were not adjusted for sociodemographic characteristics, such as maternal race and ethnicity or age.

Objective:

This study sought to estimate national and state-specific prevalence of cCMV infection in the United States, adjusted for maternal race and ethnicity and maternal age group, by pooling estimates from published studies.

Design:

We searched PubMed for U.S. cCMV newborn screening studies conducted between 2003 and 2023. From included studies, we abstracted maternal race and ethnicity- and age group-stratified cCMV prevalence to estimate strata-specific pooled prevalence. We obtained strata-specific weights from live birth data.

Main Outcome Measure:

Estimated adjusted national and state-specific prevalence estimates from 2018 to 2022.

Results:

Four studies (conducted 2004-2005, 2008, 2007-2012, and 2016-2021) were included for data abstraction. Overall, infants born to non-Hispanic Black (9.3 [8.2-10.5] per 1000) or non-Hispanic American Indian and Alaska Native (8.5 [2.1-33.2] per 1000) mothers had the highest cCMV prevalence. The estimated race and ethnicity-adjusted prevalence was 4.6-4.7 per 1000 live births nationally and ranged from 3.9 to 6.5 per 1000 across states from 2018 to 2022. Southern states and Alaska consistently had the highest cCMV prevalence. The estimated maternal age group-adjusted prevalence was 4.3-4.4 per 1000 live births nationally and ranged from 3.8 to 5.1 per 1000 across states from 2018 to 2022.

Conclusions:

States with larger proportions of racial and ethnic minorities had higher estimated prevalence of cCMV infection compared to states with larger proportions of White persons. These estimates may be useful for informing cCMV surveillance at the jurisdiction level and developing tailored, culturally relevant education and prevention strategies for persons at higher risk.
Primary HPV screening compared with other cervical cancer screening strategies in women with HIV: a cost-effectiveness study
Authors: Zhao Ran , Sanstead Erinn , Alarid-Escudero Fernando , Huchko Megan , Silverberg Michael , Smith-McCune Karen , Gregorich Steven E. , Leyden Wendy , Kuppermann Miriam , Sawaya George F. , Kulasingam Shalini
Published: September 2024

Objective:

To compare the model-predicted benefits, harms, and cost-effectiveness of cytology, cotesting, and primary HPV screening in US women with HIV (WWH).

Design:

We adapted a previously published Markov decision model to simulate a cohort of US WWH.

Setting:

United States.

Subjects, participants:

A hypothetical inception cohort of WWH.

Intervention:

We simulated five screening strategies all assumed the same strategy of cytology with HPV triage for ASCUS for women aged 21–29 years. The different strategies noted are for women aged 30 and older as the following: continue cytology with HPV triage, cotesting with repeat cotesting triage, cotesting with HPV16/18 genotyping triage, primary hrHPV testing with cytology triage, and primary hrHPV testing with HPV16/18 genotyping triage.

Main outcome measure(s):

The outcomes include colposcopies, false-positive results, treatments, cancers, cancer deaths, life-years and costs, and lifetime quality-adjusted life-years.

Results:

Compared with no screening, screening was cost-saving, and >96% of cervical cancers and deaths could be prevented. Cytology with HPV triage dominated primary HPV screening and cotesting. At willingness-to-pay thresholds under $250 000, probabilistic sensitivity analyses indicated that primary HPV testing was more cost-effective than cotesting in over 98% of the iterations.

Conclusions:

Our study suggests the current cytology-based screening recommendation is cost-effective, but that primary HPV screening could be a cost-effective alternative to cotesting. To improve the cost-effectiveness of HPV-based screening, increased acceptance of the HPV test among targeted women is needed, as are alternative follow-up recommendations to limit the harms of high false-positive testing.
Application of Ultrasonic Bone Scalpel in Surgery for Masticatory Muscle Tendon—Aponeurosis Hyperplasia
Authors: Mitsugi Sho , Habu Manabu , Yoshioka Izumi , Sasaguri Masaaki
Published: September 2024

Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a disease that presents as a hard trismus due to hyperplasia of the masseter and temporalis aponeurosis. Standard surgical methods for MMTAH include masseter resection, temporalis aponeurosis, and coronoidectomy. The operation of resecting the tendon aponeurosis attached to the posterior surface of the coronoid process carries the risk of bleeding and nerve damage because it cannot be observed directly. Therefore, the authors introduce a safer method by using an ultrasonic bone scalpel for this procedure. The authors used an ultrasonic bone scalpel with a long neck blade to scrape the posterior side of the coronoid process from the bottom to the top. The authors have treated 4 cases using this technique, and in all cases, the surgical procedure was performed safely and easily. In conclusion, ultrasonic bone scalpels are effective in MMTAH surgery for removing the attachment of the stiffened temporalis muscle tendon and aponeurosis.
Strategy of Out-Fold Double Eyelid Corrected Into In-Fold: Low Position Design, Direction Control Suture, and Fat Transfer
Authors: Ji Chenyang , Liu Shanchen , Min Fuli
Published: September 2024

Background:

Double eyelid surgery is a common but delicate cosmetic procedure in Asia. Because of the precise requirements and technical reasons, patients who received blepharoplasty may not satisfied with their out-fold crease. Some patients are born with unsatisfied out-fold double eyelids. The medial creases of double eyelid were higher than should be.

Objectives:

In this study, the authors developed a strategy to correct out-fold crease of double eyelid to in-fold to satisfy patients’ requirements.

Methods:

From January 2022 to May 2024, 102 patients (96 females and 6 males) were included in this retrospective analysis. Patients with out-fold double-eyelid inborn or obtained. The patients were divided into 3 groups: inborn out-fold double-eyelid, obtained double-eyelid with epicanthus, and obtained double-eyelid without epicanthus. The surgical strategy contained low position design, direction control suture, and fat transfer. Preoperative and postoperative images were collected, and patients’ satisfaction and complications were evaluated.

Results:

In total, 102 consecutive patients were included in this study, with an average follow-up of 11.9 months. Eleven patients had inborn out-fold creases, and 83 patients had out-fold creases with epicanthus after primitive blepharoplasty, and 8 patients had out-fold creases without epicanthus after primitive blepharoplasty. Ninety-six (94.12%) patients were satisfied with their results. Complications included narrow double eyelid width (n =1, 0.98%), asymmetric creases (n=2, 1.96%), incompletely in-fold creases (n=3, 2.94%), and subtle fork in medial creases (n=4, 3.92%).

Conclusions:

The surgical strategy, which contained low-position design, direction control suture, and fat transfer, could correct out-fold creases of double-eyelid into in-fold effectively.
Microtia and Social Media: How Can We Help Our Patients?
Authors: Arslan Muhammad , Cottone Chloe , Mangona Erinn , Rafizadeh Andre , Mohsin Marium , Frey Jordan
Published: September 2024

In today’s digital era, the intersection of social media and healthcare has emerged as a valuable tool for medical communication and education. However, the use of social media among microtia families has not been thoroughly explored in literature. The purpose of this study was to evaluate the presence of microtia surgeons on social media, the attitudes of microtia families towards physician social media use, and the motivations behind social media usage among microtia families. This study employed a cross-sectional survey methodology. Self-administered questionnaires were used to assess microtia families present in dedicated Instagram and Facebook groups, whereas the presence of microtia surgeons was assessed through responses from an official WhatsApp group. The findings reveal a significant disparity between the demand for microtia surgeons’ social media presence and their actual engagement. Although 90.5% of microtia family respondents believed that microtia surgeons should have a presence on social media platforms, only 46.0% of microtia surgeons maintained an active presence. Of microtia families, 55% expressed that they used social media both to facilitate interactions with other families and explore treatment options. Microtia surgeons more often utilized Instagram and Twitter than microtia families. Of microtia families, 40.5% reported using a combination of social media platforms, most often Facebook. This study underscores the increasing reliance on social media for medical information. By increasing their social media presence, microtia surgeons can not only enhance patient education and satisfaction but also contribute to the broader landscape of medical communication and education in the digital age.
KLF15 ATTENUATES LIPOPOLYSACCHARIDE-INDUCED APOPTOSIS AND INFLAMMATORY RESPONSE IN RENAL TUBULAR EPITHELIAL CELLS VIA PPARΔ
Authors: Shao Yili , Li Xiaojun , Zhou Wang , Qian Shaojie , Wang Ligang , Fang Xiangming
Published: September 2024

Background: The kidney is the most commonly affected organ in sepsis patients, and Krüppel-like transcription factor 15 (KLF15) has a kidney-protective effect and is highly enriched in the kidneys. This study aims to explore the role of KLF15 in sepsis-related acute kidney injury. Methods: A septic injury model in HK2 cells was established through the administration of lipopolysaccharide (LPS), followed by the transfection of an overexpression plasmid for KLF15. Cell viability was assessed using Cell Counting Kit-8 assay, and apoptosis was measured via flow cytometry. The levels of inflammatory cytokines were detected using ELISA, and western blot assay was employed to assess the expression of KLF15, PPARδ, as well as inflammatory and apoptosis-related proteins. The interaction between KLF15 and PPARδ was confirmed through the utilization of online databases and immunoprecipitation experiments. The mechanism was further validated using PPARδ agonists and small interfering RNA. Results: LPS-induced HK2 cells showed downregulated expression of KLF15 and PPARδ, along with decreased viability, accompanied by increased levels of apoptosis, TNFα, IL-1β, and IL-6. Additionally, LPS upregulated the expression of Bax, cytoplasmic cytochrome C [Cytc (cyt)], Cox-2, and p-NF-κB-p65 in HK2 cells, while simultaneously downregulating the expression of Bcl2 and mitochondrial cytochrome c [Cytc (mit)]. immunoprecipitation experiment revealed a possible interaction between KLF15 and PPARδ in HK2 cells. Ov-KLF15, Ov-PPARδ, or administration of PPARδ agonists effectively alleviated the aforementioned alterations induced by LPS. However, interference with PPARδ significantly attenuated the protective effect of Ov-KLF15 on HK2 cells. Conclusion: KLF15 attenuates LPS-induced apoptosis and inflammatory responses in HK2 cells via PPARδ.
Sex-based utilization and outcomes of cold-stored whole blood for trauma resuscitation: Analysis of a prospective multicenter study
Authors: Gallagher Shea , Dilday Joshua , Ugarte Chaiss , Park Stephen , Siletz Anaar , Matsushima Kazuhide , Schellenberg Morgan , Inaba Kenji , Hazelton Joshua P. , Oh John , Gurney Jennifer , Martin Matthew J. ,   the EAST Whole Blood Multicenter Collaborative
Published: September 2024

BACKGROUND

Resuscitation with cold-stored whole blood (WB) has outcome benefits, but benefits varied by patient sex is unknown. There are also concerns about alloimmunization risk for premenopausal females given WB, leading to some protocols excluding this cohort. We sought to analyze WB utilization, outcomes, and disparities by patient sex.

METHODS

This is a secondary analysis of a prospective multicenter study of WB resuscitation. Patients were stratified by sex and compared by transfusion strategy of WB or component therapy (CT). Generalized estimated equation models using inverse probability of treatment weighting were utilized.

RESULTS

There were 1,617 patients (83% male; 17% female) included. Females were less likely to receive WB versus males (55% vs. 76%; p < 0.001), with wide variability between individual centers (0%–33% female vs. 66%–100% male, p < 0.01). Male WB had more blunt trauma (45% vs. 31%) and higher shock index (1.0 vs. 0.8) compared with the male CT cohort (all p < 0.05) but similar Injury Severity Score. The female WB cohort was older (53 vs. 36) and primarily blunt trauma (77% vs. 62%) compared with the female CT cohort (all p < 0.05) but had similar shock index and Injury Severity Score. Male WB had lower early and overall mortality (27% vs. 42%), but a higher rate of acute kidney injury (16% vs. 6%) vs. the male CT cohort (all p < 0.01). Female cohorts had no difference in mortality, but the WB cohort had higher bleeding complications. Whole blood use was independently associated with decreased mortality (OR, 0.6; p < 0.01) for males but not for females (OR, 0.9; p = 0.78).

CONCLUSION

Whole blood was independently associated with a decreased mortality for males with no difference identified for females. Whole blood was significantly less utilized in females and showed wide variability between centers. Further study of the impact of patient sex on outcomes with WB and WB utilization is needed.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
Higher energy delivery is associated with improved long-term survival among adults with major burn injury: A multicenter, multinational, observational study
Authors: Stewart Barclay T. , Pham Tam , Cancio Leopoldo , O'Keefe Grant , Nordlund Megan J. , Day Andrew G. , Heyland Daren K.
Published: September 2024

BACKGROUND

Numerous feeding strategies have been used to mitigate the catabolism of major burn injury. Whether higher energy and/or protein delivery results in better long-term outcomes is unknown.

METHODS

We performed a secondary analysis of data from adults with major burn injuries enrolled in the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury at 54 burn centers in 18 countries. The sample was restricted to those who were mechanically ventilated within 72 hours of injury and for ≥7 days. Our key exposure was adequacy of energy, and protein ([Delivered
i
/Prescribed
i
] × 100) was categorized into three groups each: low, 0% to 50%; moderate, ≥50% to 79%; and high, ≥80%. We also analyzed adequacy using restricted cubic splines. Primary and secondary outcomes included 6-month mortality and functional outcomes (i.e., 36-Item Short-Form Health Survey, Katz Index of Independence in Activities of Daily Living, Lawton Activities of Daily Living scores), respectively. Regression models were adjusted for age, body mass index, Charlson Comorbidity Index, baseline Acute Physiology and Chronic Health Evaluation II and modified Sequential Organ Failure Assessment scores, burn size, energy/protein adequacy, and study site.

RESULTS

A total of 493 participants met the cohort restriction criteria; 336 participants were alive at 6 months. 36-Item Short-Form Health Survey, Katz Index of Independence in Activities of Daily Living, and Lawton Instrumental Activities of Daily Living Scale were completed by 218, 216, and 215 participants, respectively. The mean ± SD age was 48 ± 17 years, and 74% were male. The mean ± SD burn size was 41% ± 18% total body surface area. Participants who received 25% of recommended calories had nearly four times the hazard of death during the 6-month follow-up period than participants who received 100% of prescribed calories (adjusted hazard ratio, 3.89; 95% confidence interval, 1.35–11.20) (p = 0.02). There was no significant association between protein and 6-month mortality or energy/protein delivery and 6-month functional outcomes.

CONCLUSION

There was a positive association between higher doses of energy and 6-month survival. This relationship conflicts somewhat with several energy studies among critically ill and non–burn-injured patients. The lack of consistent evidence on optimal nutrition for critically injured patients, a fundamental component of burn care, suggests potential for a randomized trial of lower versus higher energy to improve long-term outcomes after burn injury.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Downregulation of Tumor Suppressor Gene LKB1 During Severe Primary Graft Dysfunction After Human Lung Transplantation: Implication for the Development of Chronic Lung Allograft Dysfunction
Authors: Rahman Mohammad , Scozzi Davide , Eguchi Natsuki , Klein Rachel , Sankpal Narendra V. , Sureshbabu Angara , Fleming Timothy , Hachem Ramsey , Smith Michael , Bremner Ross , Mohanakumar Thalachallour
Published: September 2024

Background.

Severe primary graft dysfunction (PGD) after lung transplantation (LTx) is a significant risk factor for the development of bronchiolitis obliterans syndrome (BOS). Recent data from our group demonstrated that small extracellular vesicles (sEVs) isolated from the plasma of LTx recipients with BOS have reduced levels of tumor suppressor gene liver kinase B1 (LKB1) and promote epithelial-to-mesenchymal transition (EMT) and fibrosis. Here, we hypothesized that early inflammatory responses associated with severe PGD (PGD2/3) can downregulate LKB1 levels in sEVs, predisposing to the development of chronic lung allograft dysfunction (CLAD).

Methods.

sEVs were isolated from the plasma of human participants by Exosome Isolation Kit followed by 0.20-µm filtration and characterized by NanoSight and immunoblotting analysis. Lung self-antigens (K alpha 1 tubulin, Collagen V), LKB1, nuclear factor kappa B, and EMT markers in sEVs were compared by densitometry analysis between PGD2/3 and no-PGD participants. Neutrophil-derived factors and hypoxia/reperfusion effects on LKB1 levels and EMT were analyzed in vitro using quantitative real-time polymerase chain reaction and Western blotting.

Results.

LKB1 was significantly downregulated in PGD2/3 sEVs compared with no-PGD sEVs. Within PGD2/3 participants, lower post-LTx LKB1 was associated with CLAD development. Hypoxia/reperfusion downregulates LKB1 and is associated with markers of EMT in vitro. Finally, lower LKB1 levels in PGD2/3 are associated with increased markers of EMT.

Conclusions.

Our results suggest that in post-LTx recipients with PGD2/3, downregulation of LKB1 protein levels in sEVs is associated with increased EMT markers and may result in the development of CLAD. Our results also suggest that ischemia/reperfusion injury during LTx may promote CLAD through the early downregulation of LKB1.
Friends because of foes: synchronous movement within predator–prey domains
Authors: Prokopenko Christina M. , Ellington E. Hance , Robitaille Alec , Aubin Jaclyn A. , Balluffi-Fry Juliana , Laforge Michel , Webber Quinn M. R. , Zabihi-Seissan Sana , Vander Wal Eric
Published: September 2024

For prey, movement synchrony represents a potent antipredator strategy. Prey, however, must balance the costs and benefits of using conspecifics to mediate risk. Thus, the emergent patterns of risk-driven sociality depend on variation in space and in the predators and prey themselves. We applied the concept of predator–prey habitat domain, the space in which animals acquire food resources, to test the conditions under which individuals synchronize their movements relative to predator and prey habitat domains. We tested the response of movement synchrony of prey to predator–prey domains in two populations of ungulates that vary in their gregariousness and predator community: (i) elk, which are preyed on by wolves; and (ii) caribou, which are preyed on by coyotes and black bears. Prey in both communities responded to cursorial predators by increasing synchrony during seasons of greater predation pressure. Elk moved more synchronously in the wolf habitat domain during winter and caribou moved more synchronously in the coyote habitat domains during spring. In the winter, caribou increased movement synchrony when coyote and caribou domains overlapped. By integrating habitat domains with movement ecology, we provide a compelling argument for social behaviours and collective movement as an antipredator response.

This article is part of the theme issue ‘The spatial–social interface: A theoretical and empirical integration’.
Meropenem resistant Burkholderia pseudomallei - A concerning single case in Australia with no prior meropenem exposure
Authors: Sivabalan Pirathaban , Satyaputra Ferris , Gassiep Ian , Forde Brian , Frazer Jaimie , Glover Matthew , Adams Buenafe , Norton Robert
Published: September 2024

We report a case of cutaneous melioidosis in a 54-year-old male with a meropenem resistant sub-population. He was empirically treated with episodic doxycycline and trimethoprim-sulfamethoxazole, however the abscess re-accumulated. The patient had no prior exposure to meropenem. A sub-population of the isolate was meropenem resistant with an MIC>32 µg/ml and the identification was re-confirmed as B. pseudomallei. Whole genome sequencing with ARDaP analysis only revealed a resistance determinant to doxycycline and it didn’t reveal a resistance determinant to meropenem. Furthermore, no carbapenemases were detected through multiple bioinformatics tools. To date this is the first reported case in Australia of a B. pseudomallei isolate resistant to meropenem without previous carbapenem exposure.
Approximation to the phylogenetic position and morphological variability of Levanderina fissa in Acapulco Bay, with observations on diatom feeding behavior
Authors: Hernández Márquez Sinuhé , Zamudio-Resendiz María Eugenia , Nuñez-Resendiz María Luisa , Calvillo Ana Karen Balboa , Dreckmann Kurt Martin , Márquez-Valdelamar Laura Margarita , Sentíes Abel
Published: September 2024

Levanderina fissa, a globally distributed mixotrophic dinoflagellate, is known for its ability to photosynthesize and phagocytize microorganisms. This study aims to approximate the phylogenetic position and explore the morphological variability of L. fissa in Acapulco Bay, Mexico, while providing observations on its diatom feeding behavior. Phylogenetic analysis based on 28S and 18S ribosomal DNA sequences suggests the existence of a monophyletic group within the Gymnodiniales, though with low phylogenetic resolution, indicating potential cryptic species within the genus. Morphological analysis reveals variability that may be influenced by regional environmental factors. Observations on diatom ingestion provide further, albeit limited, insights into the mixotrophic behavior of L. fissa. These findings emphasize the need for further research to better understand the species' ecological role and phylogenetic position, particularly concerning its feeding strategies in tropical ecosystems.
Designing a computer-assisted diagnosis system for cardiomegaly detection and radiology report generation
Authors: Zhu Tianhao , Xu Kexin , Son Wonchan , Linton-Reid Kristofer , Boubnovski-Martell Marc , Grech-Sollars Matt , Lain Antoine D. , Posma Joram M.
Published: September 2024

Chest X-ray (CXR) is a conventional diagnostic tool for cardiothoracic assessment, boasting a high degree of costeffectiveness and versatility. However, with an increasing number of scans to be evaluated by radiologists, they can suffer from fatigue which might impede diagnostic accuracy and slow down report generation. We describe a prototype computer-assisted diagnosis (CAD) pipeline employing computer vision (CV) and Natural Language Processing (NLP) trained on the publicly available MIMICCXR dataset. We perform image quality assessment, view labelling, segmentation-based cardiomegaly severity classification, and use the output of the severity classification for large language model-based report generation. Four certified radiologists assessed the output accuracy of the CAD pipeline. Across the dataset composed of 377,100 CXR images and 227,827 free-text radiology reports, our system identified 0.18% of cases with mixedsex mentions, 0.02% of poor quality images (F1=0.81), and 0.28% of wrongly labelled views (accuracy 99.4%), furthermore it assigned views for 4.18% of images which have unlabelled views. For binary cardiomegaly classification, we achieve state-of-the-art performance of 95.2% accuracy. The inter-radiologist agreement on evaluating the report’s semantics and correctness for radiologistMIMIC is 0.62 (strict agreement) and 0.85 (relaxed agreement) similar to the radiologist-CAD agreement of 0.55 (strict) and 0.93 (relaxed). Our work found and corrected several incorrect or missing metadata annotations for the MIMIC-CXR dataset, and the performance of our CAD system suggests performance on par with human radiologists. Future improvements revolve around improved text generation and the development of CV tools for other diseases.
Alpha-synuclein misfolding as a fluid biomarker for Parkinson’s disease and synucleinopathies measured with the iRS platform
Authors: Schuler Martin , Gerwert Grischa , Mann Marvin , Woitzik Nathalie , Langenhoff Lennart , Hubert Diana , Duman Deniz , Höveler Adrian , Galkowski Sandy , Simon Jonas , Denz Robin , Weber Sandrina , Kwon Eun-Hae , Wanka Robin , Kötting Carsten , Güldenhaupt Jörn , Beyer Léon , Tönges Lars , Mollenhauer Brit , Gerwert Klaus
Published: September 2024

Misfolding and aggregation of alpha-synuclein (αSyn) plays a key role in the pathophysiology of Parkinson’s disease (PD). It induces cellular and axonal damage already in the early stages of the disease. Despite considerable advances in PD diagnostics by αSyn seed-amplification assays (SAAs), an early and differential diagnosis of PD still represents a major challenge. Here, we extended the immuno-infrared sensor (iRS) platform technology from Alzheimer’s disease (AD), in which β-amyloid misfolding was monitored as a fluid biomarker towards αSyn misfolding in PD. Using the iRS platform technology, we analyzed cerebrospinal fluid (CSF) from two independent cohorts, a discovery and a validation cohort comprising clinically diagnosed PD (n=57), atypical Parkinsonian disorders with αSyn pathology (multiple system atrophy (MSA), n= 5) or Tau pathology (corticobasal degeneration (CBD), n=5, progressive supranuclear palsy (PSP) n=9), and further disease controls (frontotemporal dementia (FTD) n=7 and other, n=51). In the discovery cohort, an AUC of 0.90, 95 %-CL 0.85 – 0.96 is obtained for the differentiation of PD/MSA vs. all controls, and in the validation cohort, an AUC of 0.86, 95 %-CL 0.80 - 0.93, respectively. In the combined dataset, the αSyn misfolding classifies PD/MSA from controls with an AUC of 0.90 (n=134, 95 %-CL 0.85 - 0.96). Using two threshold values instead of one identified people in the continuum between clearly unaffected (low misfolding group) and affected by PD/MSA (high misfolding group) with an intermediate area in between. The controls versus PD/MSA in the low vs. high misfolding group were classified with 97% sensitivity and 92% specificity.

The spectral data showed misfolding in CSF from an α-helical/random-coil secondary structure of αSyn in controls to β-sheet enriched secondary structures in PD and MSA patients. In subgroups, the iRS platform implied a potential for stratifying patients with overlapping clinical symptoms. With high accuracy, the iRS αSyn misfolding platform provides a novel diagnostic tool using body fluids for differential, biological classification of the αSyn associated disorders PD and MSA. The iRS platform, indicating directly and fast all αSyn conformers, is complementary to the αSyn SAAs, which also uses αSyn misfolding as a fluid biomarker. However, monomers amplify competent misfolded conformers in SAA over time. The iRS platform opens new avenues for the stratification of PD by a body-fluid analysis and follow-ups in the continuum of healthy to clinically impaired individuals.