bluuebunny/crossref_metadata_2025 huggingface dataset:
Laryngotracheal stenosis: a single-center retrospective analysis of endoscopic treatment strategies and recurrence
Authors: Abu Asabeh Ekhlass , Zeer Zahraa M. M. , Idkedek Mayar , Qumsieh Salam , Deeb Maher , Abu Asbeh Yousef
Published: September 2024

Background:

Laryngotracheal stenosis is a process of fibrosis that results in airway obstruction; it may be congenital or acquired. Acquired cases are due to iatrogenic, traumatic, infectious and autoimmune causes. Patients present with a spectrum of breathing difficulties that might be fatal.

Objectives:

This article presents a unique retrospective cross-sectional study of patients with laryngotracheal stenosis who had endoscopic dilatation, and some had open surgical procedures to describe the evolution after the therapy, to compare the outcomes of the dilatation in comparison to surgical interventions and associated complications in other studies, to provide knowledge to help in dealing with these patients, and to enable educated, independent patient decision-making.

Material and methods:

In this observational and descriptive study, we aimed to highlight the clinical features, management, and treatment outcomes among twenty-nine patients with laryngotracheal stenosis who were managed by open and endoscopic surgical intervention over a period of 5 years. Data were collected retrospectively from the patients’ medical records from February 2016 until July 2022 at a hospital in Jerusalem, which is a tertiary healthcare facility and the only referral center for similar cases from the West Bank, East Jerusalem, and Gaza, with a population of around 8 million. Tables and graphs are used to highlight the statistical study’s findings. Data were analyzed using Microsoft Excel software.

Results:

Twenty-nine patients were involved in the study, with an average age of 32.2 years; 51.7% of them were males. The patients had one or more chronic conditions, such as hypertension and coronary artery disease. The majority of patients (65.5%) had stenosis as a result of orotracheal intubation, and the most common site was the subglottic (68.9%). According to the Cotton–Myer classification, 44.8% of the patients were classified in grade III, 34.4% were included in grade I, 13.7% in grade II, and 6.8% in grade IV. Six patients (20.68%) received surgery for stenosis, and 23 patients had an endo-laryngeal dilatation. Restenosis happened in (58.6%). Mortality rates are almost negligible.

Conclusion:

Subglottic stenosis is still a challenging condition to manage. The authors describe a single-center experience approach dealing with these conditions. Long-term follow-up for these cases is mandatory as the recurrence rate is still high.
Deep brain stimulation for post-stroke rehabilitation in Pakistan
Authors: Idrees Muhammad , Taimuri Muskan A. , Azhar Ayesha , Khan Najam A. , Kalsoom Umme , Sajid Aiman , Akilimali Aymar
Published: September 2024

Stroke has a high prevalence in Pakistan, at an alarming rate of 250 per 100 000 people. Although various treatment options are available, they are not ideal for Pakistan due to their high cost, restricted availability, and time sensitivity. In 1997, the FDA-approved deep brain stimulation (DBS) for Parkinson’s disease and it was first performed in Pakistan in 2014. DBS has also proved effective for restoring post-stroke mobility, according to a trial from August 2023. DBS has the potential to revolutionize post-stroke rehabilitation in Pakistan; however, further research is required into its effectiveness and its limitations must be addressed first.
Mucosal infection with Tsukamurella species following nasal septum procedure: a rare case report
Authors: Sidhu Alamjeet K. , Khandelwal Shreya , Dominic Savio Francis V. , Bedi Simranjeet , Pathak Yashash D.
Published: September 2024

Introduction and importance:

Tsukamurella species are rare, aerobic, gram-positive bacteria known to cause infections, primarily in immunocompromised individuals. This case report presents a rare instance of a mucosal infection caused by Tsukamurella species following a nasal septum procedure in an immunocompetent patient.

Case presentation:

A 51-year-old man with a history of multiple hereditary exostosis, allergic rhinitis, and recent nasal fracture repair presented with persistent fevers and low back pain. Postoperatively, he developed sinus pain and small oral lesions, initially treated with antibiotics for presumed sinusitis. Despite treatment, his fever persisted, leading to an emergency department visit. Laboratory tests indicated sepsis, but a CT scan of the sinuses showed no sinusitis. Despite broad-spectrum antibiotics, the patient’s fever continued. On admission day 9, nasal endoscopy and culture identified Tsukamurella species. The patient was treated with augmentin, fluconazole, and levofloxacin, leading to the resolution of symptoms and discharge with ongoing treatment.

Clinical discussion:

Tsukamurella species are uncommon pathogens that are often associated with bacteremia in immunocompromised individuals. This case highlights the diagnostic challenges and the importance of considering unusual pathogens in postprocedural infections, even in immunocompetent patients. Accurate identification and appropriate management are critical in improving outcomes for patients with Tsukamurella infections.

Conclusion:

This case underscores the need for vigilance in diagnosing rare infections like Tsukamurella, even in immunocompetent individuals. The successful resolution with combination therapy highlights the importance of appropriate antibiotic selection in managing such infections.
Curriculum and program evaluation in medical education: a short systematic literature review
Authors: Ullah Himayat , Huma Sarwat , Yasin Ghulam , Ashraf Muhammad , Tahir-ud-Din Qazi , Shabana Hossam , Sarfraz Junaid
Published: September 2024

Medical education is constantly evolving worldwide and facing various challenges. To cope with these, continuous and fruitful evaluation of an educational program is the need of the day. This study aims to know the purpose of evaluation, various theories related to program evaluation, and different models of curriculum and program evaluation. This will help educationists evaluate their programs fruitfully and effectively according to their needs and objectives. Different search engines including Medline’s PubMed interface, Google Scholar, and Cochrane Review databases using keywords, curriculum evaluation, evaluation models, and evaluation strategies in education, were searched without any date restrictions, and 20 full-text articles were selected for review and data extraction. While reviewing the literature it was found that most of the modern educational program and curriculum evaluation models are based on the reductionist, system, and complexity theories of evaluation. The experimental/quasi-experimental model is based majorly on the linear approach and reductionism, but its drawback is that it is impractical for the whole curriculum and sometimes ethically unfavorable. Kirkpatrick’s model, Philips’ model, the CIPP model, and the logic model are based on the system and complexity theory and are more practical in medical education. Each of these models has its advantages and limitations. In this review, the authors discussed the important distinctive features of these evaluation theories and models and their applicability and usefulness in evaluating different programs and curricula.
Ogilvie syndrome with caecal perforation following cesarean section: a rare case report from Jordan
Authors: Obeidat Rawan A. , Alshwayyat Sakhr , Alshwayyat Tala , Abdulla Ahmad , Aljaafreh Almoutuz , Hanifa Hamdah
Published: September 2024

Introduction:

Ogilvie syndrome is a rare condition characterized by acute colonic dilation. In 1948, H. Ogilvie first described it in medical literature. Its incidence is estimated at 100 cases per 100 000 per year in the US. Both abdominal distention and pain are considered major symptoms.

Presentation of case:

A 32-year-old woman, 36+1 weeks pregnant, experienced labour pain and was admitted to the hospital. Upon examination, she was in labour, but the foetus was in a breech position, necessitating a caesarean section. After 36 h later, she returned to the emergency department with severe, 1-day-old diffuse abdominal pain, accompanied by moderate bilious vomiting and significant abdominal distension. Abdominal CT with contrast revealed pneumoperitoneum, abdominal wall emphysema, and pneumatosis intestinalis involving the caecum and ascending colon, suggesting bowel necrosis. Emergency laparotomy revealed a caecal perforation, which was closed surgically without resection.

Clinical discussion:

Ogilvie syndrome is more common in males but can occur in females for several reasons, including pregnancy, caesarean section, pelvic surgeries, and trauma. Several factors contribute to the occurrence of this syndrome, such as pelvic fractures and cardiac events. Surgery may be required if there is suspicion of bowel perforation or ischaemia.

Conclusion:

OS is a rare condition in women, often seen after childbirth or pelvic surgery, with an unclear cause but believed to be related to autonomic nervous system imbalance. Patients with abdominal pain and distension, without evidence of obstruction, should be evaluated for pseudo-obstruction using abdominal pelvic CT, and treatment may involve conservative measures, medication, and colonoscopic decompression.
Virtual Reality to Reduce Pain, Fatigue, and Emotional Distress in People With Cancer
Authors: Cuñado-Pradales Rebeca , Soto-Ruiz Nelia , Escalada-Hernández Paula , San Martín-Rodríguez Leticia , García-Vivar Cristina
Published: September 2024

Background

Cancer and its treatments cause symptoms such as pain, fatigue, and emotional distress, which affect the quality of life of patients at different stages of cancer. Virtual reality (VR) has emerged as a promising alternative for addressing these symptoms by immersing patients in a virtual environment that isolates them from reality.

Objective

To describe the existing evidence on the use of VR to improve pain, fatigue, and emotional distress in people with cancer at different stages of the cancer trajectory.

Methods

A scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Search was conducted in PubMed and CINAHL until October 2023.

Results

Twenty-three primary studies related to the study topic were identified, and the following information was collected: type of VR (immersive vs nonimmersive) used in oncology services, purpose (distraction, training, or relaxation), devices used (head-mounted display, headset, or virtual controller), and the environment simulated (natural environment, skill games, or educational environment). The effects of VR on pain, fatigue, and emotional distress are described, highlighting its ability to mitigate these symptoms in the short term.

Conclusions

Virtual reality has been shown to be an effective technique for reducing pain, fatigue, and emotional distress in people with cancer in the short term.

Implications for practice

Nurses can use VR as a complementary tool to promote virtual environments that improve the care for and therefore the quality of life of people with cancer.
HIV-1 Elite Controllers Are Characterized by Elevated Levels of CD69-Expressing Natural Killer Cells
Authors: Batohi Nikayla , Shalekoff Sharon , Martinson Neil A. , Ebrahim Osman , Tiemessen Caroline T. , Thobakgale Christina F.
Published: September 2024

Background:

HIV type 1 ((human immunodeficiency virus) HIV-1) elite controllers (ECs) are a rare subset of people living with HIV-1 (PLWH) who control viral replication in the absence of antiretroviral treatment (ART) and may provide a model for a functional cure. We investigated the role of natural killer (NK) cells in HIV-1 ECs from South Africa.

Methods:

Phenotypic (CD69, CD38, CD57, PD-1), functional (CD107a, IFN-γ (inferferon gamma)), and nutrient transporter profiles (glucose transporter 1, CD98) of NK cells from ECs (n = 20), viremic progressors (VPs; n = 19), PLWH on ART (n = 20), and people without HIV-1 (PWOH; n = 21) were analyzed using flow cytometry. The Kruskal–Wallis test and followed by the Mann–Whitney U test were used to determine differences among the study groups. The Spearman rank correlation coefficient was used to determine significant associations.

Results:

Compared with the other study groups, the percentage of CD69-expressing NK cells was higher in ECs, whereas the percentage of CD38-expressing NK cells was higher in VPs. Percentages of CD69+CD38− NK cells were elevated in ECs compared with VPs (P = 0.003), but were not different to PLWH on ART and PWOH. Differentiation, exhaustion, and metabolic profiles were not different in ECs compared with PLWH on ART and PWOH; however, NK cell function was lower than in PWOH.

Conclusions:

These findings demonstrate that NK cells from ECs have an activated, mature profile with low levels of immune exhaustion and a reduced metabolic phenotype suggesting functional competence. This insight could inform the development of novel immunotherapeutic strategies for treating HIV-1.
Assessing the Viability of Polycaprolactone Mesh in Bilateral Orbital Floor Reconstruction: Insights From Le Fort II Fracture Cases
Authors: Kim Min Ji , Lee Jun Suk
Published: September 2024

Objective:

This study aims to evaluate the effectiveness of pure polycaprolactone (PCL) mesh in reconstructing complex bilateral orbital floor fractures associated with Le Fort II fractures. PCL mesh is traditionally viewed as less suitable for severe fractures due to its perceived weakness. This study challenges that perception by demonstrating the utility of PCL mesh in high-severity cases.

Materials and Methods:

Two patients with Le Fort II fractures and bilateral orbital floor fractures underwent orbital reconstruction using a 3D-printed PCL mesh. The mesh was molded and inserted through subciliary or transconjunctival incisions. Orbital volumes were analyzed preoperatively and postoperatively using CT scans and a 3D Analysis program.

Results:

Both cases demonstrated significant correction of orbital volume differences postoperatively, leading to improved symmetry and successful reconstruction. For case 1, the preoperative orbital volume difference of 3.2 cc was reduced to 1.1 cc postoperatively. For case 2, the preoperative orbital volume difference of 1.18 cc was reduced to 0.4 cc postoperatively. The PCL mesh provided adequate structural support and facilitated effective tissue integration. Despite the radiolucency of the PCL mesh on CT scans, volumetric analysis confirmed stable and balanced orbital volumes.

Conclusions:

Pure PCL mesh is a viable alternative for orbital floor reconstruction in severe craniofacial fractures, offering a balance of structural support and biocompatibility. To validate these findings, further research with larger samples and long-term follow-up is recommended.
Surgical Exploration of Lingual Mandibular Bone Depression (Stafne Bone Cavity)
Authors: Zhong Yuhao , Tian Yuanye
Published: September 2024

Lingual mandibular bone depression, also known as the Stafne bone cavity, commonly presents as an asymptomatic unilocular cyst-like radiolucency located below the mandibular canal. Surgical exploration of this lesion is relatively rare in the literature. A 49-year-old male was admitted to the hospital for a space-occupying lesion located in the right mandibular angle region and was performed surgical exploration. The content of the lesion was excised and prepared for histologic investigation, which revealed fibrous connective tissue, adhering muscle and nervous tissue with no evidence of epithelium tissue. Thus, the lesion was diagnosed as lingual mandibular bone depression. Of the various theories of the etiology of lingual mandibular bone depression, the most popular “glandular theory” seemed to be inapplicable in the present case. Providing misleading information in this case, B-mode ultrasonography was proved to be of little help in diagnosing this lesion.
Prevalence and Risk Factors for Malignant Nodal Involvement in Early Esophago-Gastric Adenocarcinoma
Authors: Pucher Philip H. , Rahman Saqib A. , Bhandari Pradeep , Blencowe Natalie , Chidambaram Swathikan , Crosby Tom , Evans Richard P.T. , Griffiths Ewen A. , Kamarajah Sivesh K. , Markar Sheraz R. , Trudgill Nigel , Underwood Timothy J. , Gossage James A. ,   on behalf of the CONGRESS collaborative
Published: September 2024

Objective:

The aim of this study was to quantify lymph node metastasis (LNM) risk and outcomes following treatment of early esophago-gastric (EG) adenocarcinoma.

Background:

The standard of care for early T1N0 EG cancer is endoscopic resection (ER). Radical surgical resection is recommended for patients perceived to be at risk of LNM. Current models to select organ-preserving versus surgical treatment are inconsistent.

Methods:

CONGRESS is a UK-based multicenter retrospective cohort study. Patients diagnosed with clinical or pathological T1N0 EG adenocarcinoma from 2015 to 2022 were included. Outcomes and rates of LNM were assessed. Cox regression was performed to assess the impact of prognostic and treatment factors on overall survival.

Results:

A total of 1601 patients from 26 centers were included, with median follow-up 32 months (IQR 14–53). 1285/1612 (80.3%) underwent ER, 497/1601 (31.0%) underwent surgery. Overall rate of LNM was 13.5%. On ER staging, tumour depth (T1bsm2-3 17.6% vs T1a 7.1%), lymphovascular invasion (17.2% vs 12.6%), or signet cells (28.6% vs 13.0%) were associated with LNM. In multivariable regression analysis, these were not significantly associated with LNM rates or survival. Adjusting for demographic and tumour variables, surgery after ER was associated with significant survival benefit, HR 0.33 (0.15–0.77), P=0.010.

Conclusions:

This large multicenter data set suggests that early EG adenocarcinoma is associated with significant risk of LNM. These data are representative of current real clinical practice with ER-based staging, and suggests previously held beliefs regarding reliability of predictive factors for LNM may need to be reconsidered. Further research to identify patients who may benefit from organ-preserving versus surgical treatment is urgently required.
Medical and neurologic management of brain tumor patients
Authors: Ospina Juan Pablo , Wen Patrick Y.
Published: September 2024

Purpose of review

This article discusses commonly encountered medical and neurological complications in patients with brain tumors and highlights recommendations for their management based on updated evidence.

Recent findings

Use of dexamethasone is correlated with worse prognosis in patients with glioblastoma, and in brain metastases, high doses may lead to increased side effects without additional clinical benefit. There are multiple antiseizure medications (ASM) to choose from and possible interactions and toxicity must be considered when choosing an agent. Additionally, there is growing interest in the use of AMPA receptor blockers as ASM in patients with brain tumors. Nonpharmacological strategies for the management of fatigue remain paramount. Cognitive decline is common after whole brain radiation (WBRT) and hippocampal-sparing WBRT results in superior cognitive outcomes. Venous thromboembolism is a common complication and there is growing evidence on the use of direct oral anticoagulants (DOACs) in this population.

There is evolving evidence on the management of medical and neurological complications in patients with brain tumors. These complications, require early identification and multidisciplinary collaboration and expertise.
Bacteriological profile of community peritonitis operated in a Moroccan Hospital
Authors: BAZHAR SAMIA , Benaissa Elmostafa , Ziad Fatima , Laamara Leila , Ben Lahlou Yassine , Chadli Mariama , Elouennass Mostafa
Published: September 2024

Introduction. Peritonitis is characterized by acute inflammation of the peritoneum, often resulting from digestive organ perforation or intra-abdominal septic focus. It may be either of infectious or noninfectious origin. The germs involved are those of the digestive flora (Enterobacteriaceae and Anaerobic), while gram-positive cocci and yeasts can be isolated in nosocomial infections. Our study aims to isolate and identify the germs involved in community-acquired peritonitis, in order to assess their susceptibility to the antibiotics available in our Country.
 
Methods. This is a retrospective study of bacteriological profile of community peritonitis in Rabat Morocco. A total of 150 adult patients with peritonitis, were admitted and samples were collected intraoperatively for bacteriological examination between July 1, 2022 and April 30, 2023.
 
Results. Among the 150 patients, 101 (67.8%) were males and 48 (32.2%) were females, with sex/ratio of 2.1. The mean age of the patients was 40.5 years +/- 20.12. The distribution of germs was dominated by Escherichia coli (44%). Overall, 70% of Escherichia coli isolated, had a resistance to Ampicillin but no resistance to Ampicillin has been reported by Enterococcus.
 
Discussion. In the present study, we were interested in the bacteriological profile of community peritonitis, in order to adapt the antibiotic therapy to our bacterial ecology. 
Our findings indicate a concerning trend of increasing resistance among Escherichia coli to the commonly used Amoxicillin/Clavulanic Acid combination in our clinical setting.
 
Conclusion. Consequently, there is a need to reassess the empiric antibiotic prescribed for the management of community-acquired peritonitis.
Lessons learned: drive-through COVID-19 clinic testing during an adaptive epidemic response and a point-of-care test assessment of a computer-read rapid lateral flow immunoassay with fluorescence-based detection
Authors: Rankine-Wilson Leah , Oncken Teresa , Basrewan Irshan , Jeffery Courtney , Pryce Todd M. , Wake Rebecca , Molan Aus A. L. , Paton T. F. , Inglis Tim J. J.
Published: September 2024

Background. The COVID-19 pandemic demonstrated a need for robust SARS-CoV-2 test evaluation infrastructure to underpin biosecurity and protect the population during a pandemic health emergency.

Gap statement. The first generation of rapid antigen tests was less accurate than molecular methods due to their inherent sensitivity and specificity shortfalls, compounded by the consequences of self-testing. This created a need for more accurate point-of-care SARS-CoV-2 detection methods.

Aim. Here we present the lessons-learned during the COVID-19 emergency response in Western Australia including the detailed set-up, evaluation and operation of rapid antigen test in a state-run drive-through sample collection service during the COVID-19 pandemic after the strict border shutdown ended.

Methods. We report a conformity assessment of a novel, second-generation rapid antigen test (Virulizer) comprising a technician-operated rapid lateral flow immunoassay with fluorescence-based detection.

Results. The Virulizer rapid antigen test demonstrated up to 100% sensitivity (95% CI: 61.0–100%), 91.94% specificity (95% CI: 82.5–96.5%) and 92.65% accuracy when compared to a commercial PCR assay method. Wide confidence intervals in our series reflect the limits of small sample size. Nevertheless, the Virulizer assay performance was well-suited to point-of-care screening for SARS-CoV-2 in a drive-through clinic setting.

Conclusion. The adaptive evaluation process necessary under changing pandemic conditions enabled assessment of a simple sample collection and point-of-care testing process, and showed how this system could be rapidly deployed for SARS-CoV-2 testing, including to regional and remote settings.
Latent learning without map-like representation of space in navigating ants
Authors: Clement Leo , Schwarz Sebastian , Wystrach Antoine
Published: September 2024

Desert ants are excellent navigators. Each individual learns long foraging routes meandering between the trees and bushes in their natural habitat. It is well-known how the insect brain memorizes and recognizes views, and how this recognition can guide their way. However, little is known about the rule that guide spatial learning in the first place. Here we recorded the paths of desert ants navigating in their natural habitat under various displacement conditions. We demonstrate that ants learncontinuouslythe routes they travel and memorize them in one trial, without the need for reward or punishment, and even if these routes are meandering and do not lead to places of interest: a concept called ‘latent learning’, which is typically associated with the formation of map-like representation in vertebrates. Yet, the failure of ants to solve simple artificial navigation tasks -even with the goal being clearly visible- reveals that they relied on egocentric visual memories without map-like representation of the surrounding space. Our results unveil the rules governing the formation and recall of latent memories. A model shows that it can be implemented in the insect’s Mushroom bodies brain area through dynamic interactions between short- and long-lasting memories.
Experimental Investigations of Impact Strength of Structural Wood Available in Northern Himalayas
Authors: Sheikh Ummer Amin , Jameel Azher , Koul Majid Hameed
Published: September 2024

The current paper presents the detailed investigation of impact strength of different wood species available in the northern Himalayan region of India. Wood has always provided a potential structural material for constructing different engineering structures in these hilly areas. Although some studies have been performed to determine the strength of structural wood, but individual mechanical characterization of different wood species available in these areas needs immediate attention to design safe and reliable structures. Seven different wood species that have been traditionally used for constructional purpose in northern Himalayan region of India, have been selected for investigation. Test samples of same species have been collected from different regions of this area for the purpose of experimentation. The test samples selected for experimentation were defect free and were developed in accordance with ASTM: D-143 standards. In the current work, wood samples have been seasoned naturally and it has been made sure that the moisture content of the test specimens remains below the fiber saturation point. Due to the anisotropic behavior of wood, the impact strength has been investigated along both principal loading direction i.e. parallel and perpendicular to grains.
β-catenin localization in the ctenophoreMnemiopsis leidyisuggests an ancestral role in cell adhesion and nuclear function
Authors: Walters Brian M. , Guttieres Lucas J. , Goëb Mayline , Marjenberg Stanley J. , Martindale Mark Q. , Wikramanayake Athula H.
Published: September 2024

The emergence of multicellularity in animals marks a pivotal evolutionary event which was likely enabled by molecular innovations in the way cells adhere and communicate with one another. β-catenin is significant to this transition due to its dual role as both a structural component in the cadherin-catenin complex and as a transcriptional coactivator involved in the Wnt/β-catenin signaling pathway. However, our knowledge of how this protein functions in ctenophores, one of the earliest diverging metazoans, is limited. To study β-catenin function in the ctenophoreMnemiopsis leidyi, we generated affinity-purified polyclonal antibodies targetingMlβ-catenin. We then used this tool to observe β-catenin protein localization in developingMnemiopsisembryos. In this article we provide evidence of consistent β-catenin protein enrichment at cell-cell interfaces inMnemiopsisembryos, suggesting thatMlβ-catenin had an ancestral role in cell adhesion. Additionally, we found β-catenin enrichment in some nuclei, particularly restricted to the oral pole around the time of gastrulation, suggestingMlβ-catenin may have a nuclear function inMnemiopsisembryos. TheMlβ-catenin affinity-purified antibodies now provide us with a powerful reagent to study the ancestral functions of β-catenin in cell adhesion and transcriptional regulation.
High-speed Intracellular Temperature Mapping Reveals the Existence of Non-Conductive Dissipation of Energy by Heating
Authors: Takarada Masaharu , Shirakashi Ryo , Takinoue Masahiro , Ishida Motohiko , Morita Masamune , Noji Hiroyuki , Tabata Kazuhito V. , Funatsu Takashi , Okabe Kohki
Published: September 2024

Recently, intracellular thermometry has revealed temperature variations within cells. Although the biological significance of intracellular temperature change is recognized, the physical principles of intracellular temperature change remain a mystery. Here, we investigate intracellular heat transfer through intracellular temperature mapping using a fluorescent polymeric thermometer and high-speed fluorescence lifetime imaging microscopy. Through infrared laser irradiation assisted heating, we track changes in temperature distribution to examine the mechanism of intracellular heat dissipation in relation to heat conduction. Continuous heating provokes the significantly slower (second order) relaxation of averaged temperature of single cells compared to liposomes of comparable size, and is affected by intracellular structures and molecules. Furthermore, we reveal the existence of intracellular temperature relaxation independent of heat conduction. Our results may explain the mechanisms of temperature variation in cells that are unresolved based on our current understandings, providing the first step toward unraveling intracellular thermodynamics under non-equilibrium conditions.
Triglyceride/High Density Lipoprotein Cholesterol Index and Future Cardiovascular Events in Diabetic Patients without Known Cardiovascular Disease
Authors: Nakashima Ryosuke , Ikeda Shota , Shinohara Keisuke , Matsumoto Sho , Yoshida Daisuke , Ono Yoshiyasu , Nakashima Hiroka , Miyamoto Ryohei , Matsushima Shouji , Kishimoto Junji , Itoh Hiroshi , Komuro Issei , Tsutsui Hiroyuki , Kinugawa Shintaro , Abe Kohtaro
Published: September 2024

Background

The triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index, calculated as TG levels divided by HDL-C levels, is suggested as a predictor of cardiovascular disease (CVD). We investigated the association between the TG/HDL-C index and initial CVD events in high-risk patients with type 2 diabetes mellitus (T2DM).

Methods

We analyzed the association between the TG/HDL-C index and CVD events in T2DM patients with retinopathy and hyperlipidemia without known CVD enrolled in the EMPATHY study, which compared intensive and standard statin therapy (targeting LDL-C levels <70 mg/dL and ≥100 to <120 mg/dL, respectively).

Results

A total of 4665 patients were divided into high (TG/HDL-C ≥2.5,n=2013) and low (TG/HDL-C <2.5,n=2652) TG/HDL-C index groups. During a median follow-up of 36.8 months, 260 CVD events occurred. The high TG/HDL-C index group had higher CVD risk compared to the low TG/HDL-C index group (HR 1.89, 95% CI 1.45–2.47,p<0.001). This association was consistent across various subgroups. However, a trend toward interaction between the TG/HDL-C index and EMPATHY treatment allocation for CVD risk was observed (pfor interaction=0.062). Intensive statin treatment was associated with reduced CVD risk compared to standard treatment in the high TG/HDL-C index group but not in the low group.

Conclusions

A TG/HDL-C index ≥2.5 was associated with increased CVD risk in T2DM patients with retinopathy and hyperlipidemia without a history of CVD. The TG/HDL-C index may be a predictor of CVD and indicate patients who could benefit from intensive statin treatment.
What Constitutes High Risk for Venous Thromboembolism? Comparing Approaches to Determining an Appropriate Threshold
Authors: Mittman Benjamin G , Hu Bo , Schulte Rebecca , Le Phuc , Pappas Matthew A , Hamilton Aaron , Rothberg Michael B
Published: September 2024

Background

Guidelines recommend pharmacological venous thromboembolism (VTE) prophylaxis only for high-risk patients, but the probability of VTE considered “high-risk” is not specified. Our objective was to define an appropriate probability threshold (or range) for VTE risk stratification and corresponding prophylaxis in medical inpatients.

Methods

Patients were adults admitted to any of 10 Cleveland Clinic Health System hospitals between December 2020 and August 2021 (N = 41,036). Hospital medicine physicians and internal medicine residents from included hospitals were surveyed between June and November 2023 (N = 214). We compared five approaches to determining a threshold: decision analysis, maximizing the sensitivity and specificity of a logistic regression model, deriving a probability from a point-based model, surveying physicians’ understanding of VTE risk, and deriving a probability from physician behavior. For each approach, we determined the probability threshold above which a patient would be considered high-risk for VTE. We applied each threshold to the Cleveland Clinic VTE risk assessment model (CCM) and calculated the percentage of the 41,036 patients in our cohort who would be considered eligible for prophylaxis due to their high-risk status. We compared these hypothetical prophylaxis rates with physicians’ observed prophylaxis rates.

Results

The different approaches yielded thresholds ranging from 0.3% to 5.4%, corresponding inversely with hypothetical prophylaxis rates of 0.2% to 75%. Multiple thresholds clustered between 0.52% to 0.55%, suggesting an average hypothetical prophylaxis rate of approximately 30%, whereas physicians’ observed prophylaxis rates ranged from 48% to 76%.

Conclusions

Multiple approaches to determining a probability threshold for VTE prophylaxis converged to suggest an optimal threshold of approximately 0.5%. Other approaches yielded extreme thresholds that are unrealistic for clinical practice. Physicians prescribed prophylaxis much more frequently than the suggested rate of 30%, indicating opportunity to reduce unnecessary prophylaxis. To aid in these efforts, guidelines should explicitly quantify high-risk.
Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial maturity
Authors: O'Loughlin Evan , Zhang Youwen , Chiasson-MacKenzie Christine , Dave Preshita , Rheinbay Esther , Stott Shannon L , McClatchey Andrea I
Published: September 2024

Epithelial cancers disrupt tissue architecture and are often driven by mutations in genes that normally play important roles in epithelial morphogenesis. The intrahepatic biliary system is an epithelial tubular network that forms within the developing liver via the de novo initiation and expansion of apical lumens. Intrahepatic biliary tumors are often driven by different types of mutations in the FGFR2 receptor tyrosine kinase which plays important roles in epithelial morphogenesis in other developmental settings. Using a physiologic and quantitative 3D model we have found that FGFR signaling is important for biliary morphogenesis and that oncogenic FGFR2 mutants disrupt biliary architecture. Importantly, we found that both the trafficking and signaling of normal FGFR2 and the phenotypic consequences of FGFR2 mutants are influenced by the epithelial state of the cell. Unexpectedly, we found that different tumor-driving FGFR2 mutants disrupt biliary morphogenesis in completely different and clinically relevant ways, informing our understanding of morphogenesis and tumorigenesis and highlighting the importance of convergent studies of both.
Convergent and lineage-specific genomic changes contribute to adaptations in sugar-consuming birds
Authors: Osipova Ekaterina , Ko Meng-Ching , Petricek Konstantin M. , Yung Wa Sin Simon , Brown Thomas , Winkler Sylke , PIppel Martin , Jarrells Julia , Weiche Susanne , Mosbech Mai-Britt , Taborsak-Lines Fanny , Wang Chuan , Contreras-Lopez Orlando , Olsen Remi-Andre , Ewels Phil , Mendez Aranda Daniel , Gaede Andrea , Sadanandan Keren , Weijie Low Gabriel , Monte Amanda , Ballerstaedt Ninon , Adreani Nicolas M. , Mentesana Lucia , von Bayern Auguste , Rico-Guevara Alejandro , Edwards Scott , Altshuler Douglas , Buttemer William A. , Frankl-Vilches Carolina , Kuhl Heiner , Bakker Antje , Gahr Manfred , Schupp Michael , Baldwin Maude W. , Hiller Michael , Sackton Timothy B.
Published: September 2024

Although high-sugar diets are associated with metabolic diseases in humans, several bird lineages have independently evolved to primarily subsist on simple sugars from flower nectar or fruits. In this study, we address a key question of the repeatability of molecular evolution by investigating the convergent and lineage-specific molecular mechanisms underlying dietary adaptations in four major sugar-consuming bird lineages: hummingbirds, parrots, honeyeaters, and sunbirds. We assembled nine new genomes for sugar-consuming species and their closely related non-sugar feeding outgroup species and generated 90 tissue-specific transcriptomes for six key species. We identified signatures of positive selection in both protein-coding and non-coding regulatory sequences, and found positive selection targets the same genes more frequently in sugar-feeders compared to non-sugar feeding controls, suggesting that adapting to a high-sugar diet requires changes in a limited number of genetic elements. At the functional level, pathways associated with energy homeostasis, carbohydrate metabolism, heart function, and hormonal regulation showed convergent selection signals in both protein-coding and regulatory evolution, while lipid and amino acid metabolism demonstrated mostly regulatory evolution. Notably, we observed striking evidence for convergent adaptation in MLXIPL, a transcription factor regulating sugar and lipid homeostasis, manifesting in both sequence and regulatory changes across all sugar-feeders. With functional assays, we demonstrated that hummingbird MLXIPL enhances sugar-induced transcriptional activity in HEK239 cells, suggesting its central role in the evolution of adaptations to high-sugar diets. Our findings elucidate the main genomic targets in the evolution of sugar-feeding at both molecular and pathway levels.
Architectural Immunity: ants alter their nest networks to fight epidemics
Authors: Leckie Luke , Andon Mischa Sinha , Bruce Katherine , Stroeymeyt Nathalie
Published: September 2024

In animal groups, spatial heterogeneities shape social contact networks, thereby influencing the transmission of infectious diseases. Active modifications to the spatial environment could thus be a potent tool to mitigate epidemic risk. We tested whetherLasius nigerants modify their nest architecture in response to pathogens by introducing controlor pathogen-treated individuals into nest-digging groups, and monitoring three-dimensional nest morphogenesis over time. Pathogen exposure led to an array of architectural changes including faster nest growth, increased spacing between entrances, transmission-inhibitory changes in overall nest network topology, and reduced chamber centrality. Simulations confirmed that these changes reduced disease spread. These results provide evidence for architectural immunity in a social animal and offer insights into how spatial organisation can be leveraged to decrease epidemic susceptibility.
Diel and seasonal rhythmicity in activity and corticosterone in an Arctic migratory herbivore: A multifaceted approach
Authors: de Jong Margje E. , Slettenhaar Annabel J. , Fokkema Rienk W. , Leh Marion , Verhoeven Mo A. , Griffin Larry , Millesi Eva , Moe Børge , Barnreiter Elisabeth , Loonen Maarten J.J.E. , Scheiber Isabella B.R.
Published: September 2024

Birds that migrate from temperate areas to the Arctic to breed lose their strongestZeitgeberof circadian organization when they cross the Arctic circle in spring: the 24h light-dark cycle. Under continuous daylight, diverse behavioural and physiological patterns have been detected in both free-ranging and laboratory animals. To better understand the evolution of plasticity in circadian clocks, it is essential to study behavioural and physiological rhythmicity in the context of a species’ ecology. Employing a multifaceted approach, which included wildlife cameras, accelerometers, and non-invasive sampling of hormone metabolites, we investigated activity patterns and corticosterone rhythmicity in a migratory herbivore, the barnacle goose (Branta leucopsis), during its Arctic breeding season in Svalbard. We found that females showed a combination of both ultradian and diel rhythmicity in nest recesses and sleep during incubation. In both parents, these rhythms in activity continued also during the gosling rearing period. During moult, many geese aligned activity with the tidal rhythm. Barnacle geese showed weak diel rhythmicity in excreted corticosterone metabolites. This suggests that while Arctic geese may adopt an alternativeZeitgeberduring the Arctic summer to maintain a diel rhythm, ultradian rhythmicity remains essential, allowing the geese to flexibly adjust their rhythms to environmental conditions.
Ketone Body Metabolism is Not Required for Improvement of Heart Failure by Ketogenic Diet in Mice
Authors: Foulks Zachary , Weinheimer Carla J. , Kovacs Attila , Michael Jessica , Pyles Kelly D. , Menezes Thiago N. , Cho Kevin , Patti Gary J. , McCommis Kyle S.
Published: September 2024

Failing hearts increasingly metabolize ketone bodies, and enhancing ketosis improves heart failure (HF) remodeling. Circulating ketones are elevated by fasting/starvation, which is mimicked with a high-fat, low-carbohydrate “ketogenic diet” (KD). While speculated that KD improves HF through increased ketone oxidation, some evidence suggests KD paradoxically downregulates cardiac ketone oxidation despite increased ketone delivery. We sought to clarify the significance of cardiac ketone metabolism during KD in HF. Mice were subjected to transverse aortic constriction with apical myocardial infarction (TAC-MI) and fed either low-fat (LF) control or KD. Cardiac-specific mitochondrial pyruvate carrier 2 (csMPC2-/-) mice were used as a second model of heart failure. In both mice, feeding a KD improved HF, determined by echocardiography, heart weights, and gene expression analyses. Although KD increases plasma ketone bodies, gene expression for ketone metabolic genes is decreased in the hearts of KD-fed mice. Cardiac-specific β-hydroxybutyrate dehydrogenase 1 (csBDH1-/-), the first enzyme in ketone catabolism, mice were also studied and crossed with the csMPC2-/-mice to create double knockout (DKO) mice. These mice were aged to 16 weeks and switched to LF or KD, and KD was able to completely normalize the hearts of both csMPC2-/- and DKO mice, suggesting that ketone metabolism is unnecessary for improving heart failure with ketogenic diet. These studies were then repeated, and mice injected with U-13C-β-hydroxybutyrate to evaluate ketone metabolism. KD feeding significantly decreased the enrichment of the TCA cycle from ketone body carbons, as did the BDH1-deletion in DKO mice. Gene expression and respirometry suggests that KD instead increases cardiac fat oxidation. In conclusion, these results suggest that ketogenic diet decreases cardiac ketone metabolism and does not require ketone metabolism to improve heart failure.
Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system
Authors: Hana Tadros A. , Mousa Veronika G. , Lin Alice , Haj-Hussein Rawan N. , Michael Andrew H. , Aziz Madona N. , Kamaridinova Sevinch U. , Basnet Sabita , Ormerod Kiel G.
Published: September 2024

Huntington’s Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed with varying polyQ lengths, non-pathogenic-htt (Q15, NP-htt) and pathogenic-htt (Q138, P-htt), with an N-terminal RFP tag forin vivovisualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 hours post hatching and significant aggregates form in the segmental nerve branches at 48 hours post hatching. Organelle trafficking up-and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.
A Phylogenetic Model of Established and Enabled Biome Shifts
Authors: McHugh Sean W. , Donoghue Michael J. , Landis Michael J.
Published: September 2024

Where each species actually lives is distinct from where it could potentially survive and persist. This suggests that it may be important to distinguish established from enabled biome affinities when considering how ancestral species moved and evolved among major habitat types. We introduce a new phylogenetic method, called RFBS, to model how anagenetic and cladogenetic events cause established and enabled biome affinities (or, more generally, other discrete realized versus fundamental niche states) to shift over evolutionary timescale. We provide practical guidelines for how to assign established and enabled biome affinity states to extant taxa, using the flowering plant clade Viburnum as a case study. Through a battery of simulation experiments, we show that RFBS performs well, even when we have realistically imperfect knowledge of enabled biome affinities for most analyzed species. We also show that RFBS reliably discerns established from enabled affinities, with similar accuracy to standard competing models that ignore the existence of enabled biome affinities. Lastly, we apply RFBS to Viburnum to infer ancestral biomes throughout the tree and to highlight instances where repeated shifts between established affinities for warm and cold temperate forest biomes were enabled by a stable and slowly-evolving enabled affinity for both temperate biomes.