bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary exophytic urothelial carcinoma of the bladder: A case report
Authors: Li Liangliang , Liu Kun , Ma Xueping , Wu Yameng , Wang Changxi , Wang Yangang
Published: August 2024

Rationale:

Bladder urothelial carcinoma (UC) is a common urinary system tumor that is generally diagnosed by cystoscopy combined with pathological biopsy. However, complete exophytic UC of the bladder is very rare and difficult to diagnose. Early diagnosis and accurate identification of such tumors, followed by aggressive surgical treatment, is essential for the management of these patients.

Patient concerns:

An 84-year-old man was admitted to the hospital with dysuria, a poor diet, and significant weight loss.

Diagnosis:

Pelvic computed tomography and magnetic resonance imaging revealed an exteriophytic round mass on the right lateral wall of the bladder. Cystoscopy revealed a necrotic mass on the right lateral wall of the bladder cavity, and no tumor cells were found following the biopsy. The tumor was removed via partial cystectomy, and the pathological result indicated high-grade muscle-invasive UC.

Interventions:

The patient refused radical cystectomy and underwent laparoscopic partial cystectomy plus pelvic lymph node dissection followed by cisplatin plus gemcitabine chemotherapy.

Outcomes:

The patient’s mental state and appetite were significantly improved after the urinary tube was removed 1 week after surgery. His general state was significantly improved after 1 month of follow-up but died of acute cerebral infarction 3 months after surgery.

Lessons:

UC of the bladder may grow completely out of the bladder without symptoms such as gross hematuria; thus, early diagnosis is difficult. For high-risk individuals, regular imaging tests may help to detect tumors early. Partial cystectomy is a reliable surgical modality for bladder preservation in such patients.
The relationship between workplace justice and self-evaluated nonfatal occupational accidents among healthcare employees in Taiwan: An observational study
Authors: Hsieh Ching-Mei , Chen Sheryl , Peng Tsu-Te , Chen Po-Han , Chen Albert , Chen Chieh-Jan
Published: August 2024

The relationship between workplace justice and nonfatal occupational accidents in a single-payer healthcare system has rarely been explored. As countries strive to achieve and sustain universal health coverage, healthcare workers’ occupational safety and health require greater concerns. We used the data from a national survey conducted on randomly sampled Taiwanese workers. One hundred forty eight males and 567 females, with a total of 715 healthcare workers aged 20 to 65, were analyzed. The workplace scale consisted of 4 subcomponents, including distributive justice, interpersonal justice, information justice, and procedural justice, and was dichotomized into low and high groups in each dimension. Logistic regression models examined the relationship between workplace justice and self-evaluated occupational accidents among healthcare employees. The prevalence of self-evaluated occupational accidents in healthcare employees was 15.54% and 11.64% for men and women, respectively. After adjusting variables such as sociodemographic variables, physical job demands, shift work status, work contract, and psychological job demands, regression analyses indicated that health employees with lower distributive justice, interpersonal justice, information justice, and procedural justice were significantly associated with self-evaluated occupational accidents both in males and females. Expanding the study to include healthcare systems in different countries could enhance the generalizability of the findings. Offering specific recommendations for policymakers and healthcare administrators to improve workplace justice and reduce occupational accidents.
Analysis of risk factors affecting postoperative neurological recovery in patients with cervical spine fracture in ankylosing spondylitis
Authors: Wang Can , Li Yang , Wang Liang , Wang Yijin , Gao Zhongya , Lu Xuhua
Published: August 2024

Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease that mainly affects the spine and involves the sacroiliac and peripheral joints. Low-energy trauma can often lead to spinal fractures and spinal cord injuries (SCIs), the treatment of AS is challenging. The prognosis of neurological function in patients with AS cervical fracture and SCI is a major problem that must sought clinician attention on urgent basis. A total of 106 patients with AS cervical fractures who underwent surgical treatment at Shanghai Changzheng Hospital between August 2009 and 2021 were included in this study. All the patients were divided into 2 groups (improved group and the control group) based on their neurological function improvement at 1 year mark after the surgery. The baseline characteristics, perioperative factors, and procedural outcomes of all the patients including injury type, AS drug treatment, the injured segment, ossified anterior longitudinal ligament injury, spinal hypersignal, decompression time window, operation duration, blood loss, preoperative and postoperative American Spinal Injury Association (ASIA) score were recorded and analyzed. Among the 106 patients, 79 demonstrated improved neurological function at 1 year mark after the surgery. Binary univariate logistic regression analysis revealed significant differences in injury type (P = .018), ossified anterior longitudinal ligament injury (P = .01), operation duration (P = .002), spinal hypersignal (P = .001), preoperative ASIA score (P < .001), and prior AS drug treatment (P = .012). No significant differences were observed in the other variables (P > .05). Binary multivariate logistic regression analysis identified spinal hypersignal (OR = 37.185, P = .028), preoperative ASIA score (OR = 0.16, P = .012) and previous AS drug treatment (OR = 0.296, P = .049) as factors associated with postoperative neurological function improvement. The preoperative ASIA score and previous drug treatment of AS were identified as protective factors affecting the improvement of neurological functions in patients with AS cervical fracture after surgery. Preoperative T2-weighted spinal hypersignal was identified as an independent risk factor affecting the improvement of neurological function recovery in patients with AS cervical fracture after the surgery.
A comparison of the clinical efficacy of total hip arthroplasty via direct anterior approach and posterior approach: A meta-analysis
Authors: Wang Hao , Liu Jin-Feng , Wang Fengjing , Yuan Tiange , Jiang Hengduo , Wei Zhuoqi , Zhang Yang , Meng Jiahao
Published: August 2024

Background:

The approach of total hip arthroplasty (THA) has long been controversial, and many studies have compared different approaches. However, there is still a lack of consistent conclusions and comprehensive, systematic comparisons and evaluations.

Methods:

This study retrieved 7 databases: PubMed, Web of Science, Embase, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Database. The search time ranged from the establishment of each database to November 1, 2023. Data analysis was performed using Review Manager 5.4, and outcome was presented as the weighed mean difference for continuous data and risk/odds ratio for dichotomous data. We used the Mantel–Haneszel method and random effects model to obtain the overall effects of the differences in the impact of 2 surgical methods on clinical outcomes in all included studies.

Results:

A total of 33 articles were included in this study, including 14478 participants, 4911 participants in DAA group and 9567 participants in PA group. The visual analogue scale scores of the DAA group at 1 day and 2 days after THA were significantly lower than those of the PA group (mean difference [MD] = −0.56, 95% confidence interval [CI]: −0.83 to −0.30, P < .01) at 1 day and (MD = −0.67, 95% CI: −1.16 to −0.17, P = .01) at 2 days. The risk of intraoperative fracture (odds ratio = 2.18, 95% CI: 1.11–4.29, P = .05) and lateral femoral nerve injury (risk ratio = 7.84, 95% CI: 1.69–36.42, P < .01) in the DAA group was significantly higher than that of the PA group. The number of prostheses in the Lewinnek safe zone of the DAA group was significantly higher than that of the PA group (risk ratio = 1.13, 95% CI: 1.00–1.27, P = .05). The results showed no significant difference between the DAA group and the PA group in the time to stop using walking aids, dislocation rate, groin pain, incision complications, heterotopic ossification, intraoperative blood loss, and acetabular anterior (P > .05).

Conclusion:

Compared with the PA group, patients in the DAA group showed more ideal anatomical and imaging results, shorter hospital stay, and showing advantages in postoperative pain, but with a higher incidence of intraoperative complications.
Looking backward toward the future: A bibliometric analysis of the last 40 years of meningioma global outcomes
Authors: Köse Serdal Kenan , Aydoğdu Gülçin , Demir Emre , Kiraz Murat
Published: August 2024

This study is the first comprehensive bibliometric analysis about meningioma to date. The aim of this study is to identify the most influential publications in this field through citation and co-citation analysis, to examine international collaborations, to identify the conceptual framework of the subject and emerging trending topics through keyword analysis, and to identify the most productive countries, authors and journals. 9619 articles on meningioma published between 1980 and 2023 were downloaded from the Web of Science (WoS) database and statistically analyzed. In this study, various bibliometric techniques were utilized, including trend keyword analysis, thematic evolution analysis, factor analysis, conceptual structure analysis, citation and co-citation analyses. Bibliometric network visualization maps were created to identify trend topics, citation analysis and cross-country collaborations. The Exponential Smoothing estimator was used to predict article productivity in the coming years. The first 3 countries that contributed the most to the literature were respectively; USA (2664, 27.7%), Japan (972, 10.1%), Germany (943, 9.8%). The first three most productive journals were respectively; Journal of Neurosurgery (number of article = 496), World Neurosurgery (399), Acta Neurochirurgica (378). The most productive author was Mcdermott MW (number of article = 88) and the most active institution was the University of California System (number of article = 470). In addition to high-grade meningiomas, the most studied topics from past to present have been magnetic resonance imaging, recurrence, radiation therapy, and skull base. As a result of the analyses to determine trend topics, the subjects studied in recent years were diagnostic and imaging methods, surgical and treatment methods, prognosis and survival, epidemiology and quality of life, and with the advancement of technology, machine learning and prediction models. Scientific collaboration was seen primarily in articles from western countries, especially the USA, European countries, and Canada. However, there was also a not insignificant effect in developing countries such as China, India, and Turkey.
Innovations in transplant techniques for complex anomalies
Authors: Vandendriessche Katrien , Rega Filip , Van De Bruaene Alexander
Published: August 2024

Purpose of review

With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients.

Recent findings

The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system – OCS) and hypothermic (hypothermic oxygenated perfusion – HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool.

The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.
Psychosocial Assessment Tool 2.0 and Long-term Mental Health Outcomes in Childhood Cancer
Authors: Karlson Cynthia W. , Barajas Kimberly G. , Erp Lauren S. , Winston Kaysie
Published: August 2024

To identify childhood cancer patients and their families at the greatest risk for psychosocial difficulties, this study examined the predictive validity of the Psychosocial Assessment Tool 2.0 (PAT2.0) on caregiver and patient-reported mental health outcomes at 1-year follow-up. The PAT2.0 was administered to caregivers a median of 0.08 years after cancer diagnosis. A brief psychosocial screening battery (Family Symptom Inventory and PROMIS v1.0 Pediatric Profile-25) was administered to patient-caregiver dyads (n=53) ∼1-year later. Linear regressions support the longitudinal predictive validity of the PAT2.0 for caregiver-reported child and caregiver mental health symptoms and child-reported peer relationships difficulties.
Emerging Nurse Billing and Reimbursement Models
Authors: Welton John M. , Longyear Robert
Published: August 2024

OBJECTIVES

To explore and make recommendations to implement direct billing and reimbursement models for nursing care in the United States.

BACKGROUND

Nurses make up the largest group of healthcare professionals and within hospitals, nurses represent approximately a quarter of all resources and associated costs of patient care. This care is mostly hidden in daily room and board charges.

METHODS

The authors surveyed the recent and historical literature related to costing and billing for nursing care. These results were synthesized and led to the recommendation of several new models to cost, bill, and pay for nursing care provided by nurses who are not currently billing for their services.

RESULTS

Two basic billing models are proposed: the 1st is to remove nursing care out of the current daily room or facility-based charges and allocate nursing care time provided to each patient during each day of stay. The 2nd is to expand existing Current Procedural Terminology codes to bill for specific activities and interventions by nurses in all settings where nursing care is delivered.

CONCLUSIONS

It is feasible to implement the proposed methods to identify patient-level nursing intensity, cost, services, and interventions provided by individual nurses in all healthcare settings.
Postsurgical tactile-evoked pain: a role for brain-derived neurotrophic factor-tropomyosin receptor kinase B–dependent novel tactile corpuscles
Authors: Wilson Kirsten , Sze Ying , Regan Anna , Zhu Chunyi , Mazur Katarzyna , Velichkova Atanaska N. , Torsney Carole
Published: August 2024

Introduction:

Millions of people undergo surgical procedures each year with many developing postsurgical pain. Dynamic allodynia can arise when, for example, clothing brushing close to the surgical site elicits pain. The allodynia circuits that enable crosstalk between afferent tactile inputs and central pain circuits have been studied, but the peripheral tactile drive has not been explored.

Objective:

Investigate the innervation of the skin in the rat plantar hindpaw skin–muscle incision model.

Results:

Incision increased epidermal thickness and cell layers and reduced intraepidermal nerve fibre density, identified with PGP9.5 immunostaining. Strikingly, Collagen IV immunostaining revealed the development of dermal protrusions, oriented towards the incision site, that were reminiscent of the dermal papillae that exist in glabrous footpads. S100 immunostaining for lamellar Schwann cells revealed the presence of novel tactile corpuscles (S100-positive bulb) within incision-induced putative dermal papillae. The occurrence of these novel tactile corpuscles coincided with behavioural observations of dynamic allodynia. Tactile corpuscles require brain-derived neurotrophic factor- tropomyosin receptor kinase B (BDNF-TrkB) signalling to form during development, and an increase in BDNF-immunostaining intensity was observed close to the incision site. Local acute administration of TrkB-Fc, to block BDNF-TrkB signalling, reduced, by approximately 50%, both tactile corpuscle size (S100+ bulb area) and dynamic allodynia.

Conclusion:

Surgery induces the development of novel tactile corpuscles in the incision surround, in a BDNF-TrKB–dependent manner, that contributes to postsurgical tactile-evoked pain.
Longitudinal study of cognitive function in people with HIV and toxoplasmic encephalitis or latent toxoplasma infection
Authors: Diaz Monica M. , McCutchan J. Allen , Crescini Melanie , Tang Bin , Franklin Donald , Letendre Scott L. , Heaton Robert K. , Bharti Ajay R.
Published: August 2024

Background:

Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related central nervous system (CNS) co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on neurocognitive functioning in PWH with TE compared to LTI or no toxoplasmal infection.

Methods:

PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti-toxoplamic immunoglobulin G (IgG) assay. Participants were classified into one of three groups: TE+ (n = 39), LTI+ (n = 34), LTI− (n = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit.

Results:

The mean age was 48 ± 11 years, mean educational level 13 ± 3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/ml) and had lower absolute CD4+ cell count. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI− participants.

Conclusions:

PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.
Brief Report: Switching to Long-Acting CAB/RPV: Data From an Italian Monocentric Cohort
Authors: Matone Maddalena , Piscaglia Marco , Giacomelli Andrea , Moschese Davide , Capetti Amedeo , Pozza Giacomo , Galli Lucia , Antinori Spinello , Gori Andrea , Rizzardini Giuliano , Cossu Maria Vittoria
Published: August 2024

Background:

Cabotegravir (CAB)/rilpivirine (RPV) is the first long-acting injectable (LAI) antiretroviral therapy approved for virologically suppressed adults with HIV-1.

Setting:

Italian single centre cohort.

Methods:

We conducted a retrospective observational study to assess the durability, adherence to the prescribed injection schedule, and reasons for discontinuation of CAB/RPV LAI administered every 8 weeks (Q8W).

Results:

One hundred thirty-eight patients were included with a median observation period of 43 weeks [interquartile range (IQR) 34–47 weeks]. Of these, 32 (23.2%) were female, and the median age was 51 years (IQR 40–58 years). Twelve patients (8.7%) discontinued CAB/RPV LAI treatment with a median time to discontinuation of 21 weeks (IQR 12–35 weeks), and 92.8% of the injections occurred within the CAB/RPV LAI schedule. The most common reason for discontinuation was injection-related pain (5/12). No confirmed virological failure occurred during the period of observation with 3 individuals who experienced virological blips.

Conclusions:

Our findings showed that CAB/RPV LAI Q8W is tolerated well in clinical practice, with high adherence to the injection schedule and few discontinuations mainly related to injection site–related pain.
The Association of Anemia With Survival Among People With HIV Following Antiretroviral Initiation in the NA-ACCORD 2007–2016
Authors: Lang Raynell , Coburn Sally B. , Gill M. John , Grossman Jennifer , Gebo Kelly A. , Horberg Michael A. , Mayor Angel M. , Justice Amy C. , Bosch Ronald J. , Silverberg Michael J. , Rabkin Charles S. , Sterling Timothy R. , Thorne Jennifer E. , Moore Richard D. , Althoff Keri N. ,   for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
Published: August 2024

Background:

Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America.

Methods:

Within the NA-ACCORD, annual median hemoglobin measurements between January 01, 2007, and December 31, 2016, were categorized using World Health Organization criteria into mild (11.0–12.9 g/dL men, 11.0–11.9 g/dL women), moderate (8.0–10.9 g/dL men/women), and severe (<8.0 g/dL men/women) anemia. Discrete time-to-event analyses using complementary log–log link models estimated mortality hazard ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality.

Results:

Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among men (adjusted hazard ratios = 5.8 [5.4, 6.2]) versus women (adjusted hazard ratios = 4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels decreased significantly in the 4 years before death, with a maximum decrease in the year before death. Macrocytic anemia was associated with an increased mortality risk and microcytic anemia was associated with a decreased mortality risk (vs. normocytic anemia).

Conclusions:

Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased association and microcytic anemia having a decreased association with mortality compared with normocytic anemia.
Materials modelling in the University of Limpopo
Authors: Ngoepe Phuti E. , Chadwick Alan V. , Sithole Happy M. , Mokhele Khotso D. K. , Catlow C. Richard A.
Published: August 2024

This article provides insights into building research capacity in computational modelling of materials at the University of Limpopo (UL), formerly University of the North, in South Africa, through a collaboration with a consortium of universities in the United Kingdom (UK) through the support of the National Research Foundation (NRF), formerly the Foundation for Research and Development, and the Royal Society (RS). A background that led to the choice of building research capacity at historically disadvantaged universities in South Africa, including the UL, is given. The
modus operandi
of the collaboration between the UL and several UK universities on computational modelling of materials is outlined, together with the scientific highlights that were achieved in themes of minerals, energy storage and alloy development. The capacity built in terms of human capital and institutions set up is shared, which is followed by a discussion of the continuing research activities after the formal NRF–RS collaboration ceased with more alignment to industrial applications with national and international support. We conclude by highlighting the success of the project in capacity-building and consolidating the Materials Modelling Centre with developments of high-performance computing in South Africa and the African continent. We comment on the lessons learned regarding successful capacity-building programmes.
An early warning indicator trained on stochastic disease-spreading models with different noises
Authors: Chakraborty Amit K. , Gao Shan , Miry Reza , Ramazi Pouria , Greiner Russell , Lewis Mark A. , Wang Hao
Published: August 2024

The timely detection of disease outbreaks through reliable early warning signals (EWSs) is indispensable for effective public health mitigation strategies. Nevertheless, the intricate dynamics of real-world disease spread, often influenced by diverse sources of noise and limited data in the early stages of outbreaks, pose a significant challenge in developing reliable EWSs, as the performance of existing indicators varies with extrinsic and intrinsic noises. Here, we address the challenge of modelling disease when the measurements are corrupted by additive white noise, multiplicative environmental noise and demographic noise into a standard epidemic mathematical model. To navigate the complexities introduced by these noise sources, we employ a deep learning algorithm that provides EWS in infectious disease outbreaks by training on noise-induced disease-spreading models. The indicator’s effectiveness is demonstrated through its application to real-world COVID-19 cases in Edmonton and simulated time series derived from diverse disease spread models affected by noise. Notably, the indicator captures an impending transition in a time series of disease outbreaks and outperforms existing indicators. This study contributes to advancing early warning capabilities by addressing the intricate dynamics inherent in real-world disease spread, presenting a promising avenue for enhancing public health preparedness and response efforts.
Intracranial Directed Connectivity Links Subregions of the Prefrontal Cortex to Major Depression
Authors: Myers John , Xiao Jiayang , Mathura Raissa , Shofty Ben , Pirtle Victoria , Adkinson Joshua , Allawala Anusha B. , Anand Adrish , Gadot Ron , Najera Ricardo , Rey Hernan G. , Mathew Sanjay J. , Bijanki Kelly , Banks Garrett , Watrous Andrew , Bartoli Eleonora , Heilbronner Sarah R. , Provenza Nicole , Goodman Wayne K. , Pouratian Nader , Hayden Benjamin Y. , Sheth Sameer A.
Published: August 2024

Understanding the neural basis of major depressive disorder (MDD) is vital to guiding neuromodulatory treatments. The available evidence supports the hypothesis that MDD is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neural systems lead to diminished emotion regulation and intrusive ruminations. Recent research also points towards network changes in the brain, especially within the prefrontal cortex (PFC), as primary sources of MDD etiology. However, due to limitations in spatiotemporal resolution and clinical opportunities for intracranial recordings, this hypothesis has not been directly tested. We recorded intracranial EEG from the dorsolateral (dlPFC), orbitofrontal (OFC), and anterior cingulate cortices (ACC) in neurosurgical patients with MDD. We measured daily fluctuations in self-reported depression severity alongside directed connectivity between these PFC subregions. We focused primarily on delta oscillations (1-3 Hz), which have been linked to GABAergic inhibitory control and intracortical communication. Depression symptoms worsened when connectivity within the left vs. right PFC became imbalanced. In the left hemisphere, all directed connectivity towards the ACC, from the dlPFC and OFC, was positively correlated with depression severity. In the right hemisphere, directed connectivity between the OFC and dlPFC increased with depression severity as well. This is the first evidence that delta oscillations flowing between prefrontal subregions transiently increase intensity when people are experiencing more negative mood. These findings support the overarching hypothesis that MDD worsens with prefrontal disinhibition.
Overventilation-induced airspace acidification increases susceptibility to Pseudomonas pneumonia
Authors: Felten Matthias , Tan Chunjiang , Ferencik Sebastian , Li Jingjing , Letsiou Eleftheria , Lienau Jasmin , Müller-Redetzky Holger , Hocke Andreas , Brömel Theresa C. , Gruber Achim D. , Krishnamoorthy Gopinath , Ochs Matthias , Brandenberger Christina , Zhang Qi , Kuebler Wolfgang M. , Witzenrath Martin
Published: August 2024

Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in critically ill patients. Local pH variations affect bacterial growth. Whether airway acidification contributes to the pathogenesis and pathophysiology ofPseudomonas aeruginosa(PA)-induced VAP is currently unknown. This study was undertaken to investigate the role and mechanisms of airspace acidification by mechanical ventilation (MV) in PA-induced VAP.

C57BL/6J mice were subjected to high (HVt: 34 mL/kg) or low (LVt: 9 mL/kg) tidal volume MV for 4 h. PA was instilledviathe tracheal tube, and animals were allowed to recover from sedation and breathe spontaneously for 24 h following extubation. Fluorescence microscopy was applied to determine alveolar pH in ex vivo perfused and ventilated murine lungs. Bacterial growth and adhesion on cyclically stretched A549 and human alveolar epithelial cells was examined.

Upon PA infection, HVt mice showed increased alveolo-capillary permeability, elevated lung and blood leukocyte counts, and higher bacterial load in lungs and extrapulmonary organs as compared to LVt controls. HVt MV induced acidification of alveolar lining fluid (ALF) in lungs and decreased pulmonary expression of Na+/H+exchanger 1 (NHE1). Inhibition of NHE1 enhanced PA growthin vitroon alveolar epithelial cells and increased pulmonary bacterial loads in LVt-MV micein vivo.

In a novel murine VAP model, key characteristics of PA-VAP were replicated. HVt MV induced mild VILI with acidification of airway lining fluid, increasing susceptibility to PA pneumonia. NHE1 was identified as critical factor for MV-induced airspace acidification, and thus as potential target to combat PA-VAP.
Temporal changes in surface tension guide the accurate asymmetric division of Arabidopsis zygotes
Authors: Kang Zichen , Nakagawa Sakumi , Matsumoto Hikari , Ishimoto Yukitaka , Nonoyama Tomonobu , Hanaki Yuga , Tsugawa Satoru , Ueda Minako
Published: August 2024

In most plants, the zygote divides asymmetrically to define the body axis. InArabidopsis thaliana, the zygote undergoes polar elongation maintaining a transverse band of cortical microtubules (MTs), and divides asymmetrically forming another MT band, preprophase band (PPB). How the MT band is maintained at the actively growing cell tip and whether it contributes to PPB formation remain elusive. By combining live-cell imaging and mechanical simulation, we show that zygote elongation induces a temporal change (large material derivative) in surface tension at the growing tip to maintain the MT band, which in turn supports polar elongation. The MT band then guides PPB to determine the cell division site. Therefore, autonomous mechanical feedback between cell elongation and MT organization ensures the zygote division asymmetry.
Learning sequence-based regulatory dynamics in single-cell genomics
Authors: Ibarra Ignacio L. , Schneeberger Johanna , Erdogan Ege , Redl Lennart , Martens Laura , Klein Dominik , Aliee Hananeh , Theis Fabian J.
Published: August 2024

Epigenomics assays, such as chromatin accessibility, can identify DNA-sequence-specific regulatory factors. Models that predict read counts from sequence features can explain cell-based readouts using specific DNA patterns (genomic motifs) but do not encode the changes in genomic regulation over time, which is crucial for understanding biological events during cell transitions.

To bridge this gap, we presentmuBind, a deep learning model that accurately predicts genomic counts of single-cell datasets based on DNA sequence features, their cell-based activities, and cell relationships (graphs) in a single architecture, enhancing the interpretability of cell transitions due to the possibility of inspecting motif activities weighted by nearest neighbors.

MuBindshows competitive performance in bulk and single-cell genomics. When complemented with graphs learned from RNA-based dynamical models used as injected priors in our model,muBindenhances through motif-graph interactions the identification of transcriptional regulators explaining cell transition events, including Sox9 in pancreatic endocrinogenesis scATAC-seq, and Gli3/Prdm16 in mouse neurogenesis and human organoids scRNA-seq, both supported by independent evidence, including associations between chromatin and motif activities over pseudotime, TF-gene expression patterns, and biological knowledge of these regulators.

muBindadvances our understanding of cell transitions by revealing regulatory motifs and their interactions, providing valuable insights for genomic research and gene regulatory network dynamics. It is available athttps://github.com/theislab/mubind.
Dihydroxyhexanoic acid biosynthesis controls turgor in pathogenic fungi
Authors: Kumakura Naoyoshi , Motoyama Takayuki , Miyazawa Keisuke , Nogawa Toshihiko , Yonehara Katsuma , Sakai Kaori , Ishihama Nobuaki , Matsumori Kaisei , Gan Pamela , Koshino Hiroyuki , Fukuma Takeshi , O’Connell Richard J. , Shirasu Ken
Published: August 2024

Many plant pathogenic fungi penetrate host surfaces mechanically, using turgor pressure generated by appressoria, specialized infection cells. These appressoria develop semipermeable cell walls and accumulate osmolytes internally to create turgor by osmosis. While melanin is known to be important for turgor generation, the mechanism for wall semipermeability has remained unclear. Here we identifyPKS2andPBG13, by reverse genetics, as crucial for forming the semipermeable barrier in anthracnose and rice blast fungi. These genes encode enzymes that synthesize 3,5-dihydroxyhexanoic acid polymers essential for the cell wall properties. Deleting these enzymes impairs cell wall porosity, abolishing turgor and pathogenicity without affecting melanization. Our findings uncover a novel mechanism of turgor generation, linking enzyme function to pathogen penetration and disease potential, presenting new targets for disease control.
Single-shot impulsive stimulated Brillouin microscopy by tailored ultrashort pulses
Authors: Krause David , Boehm John , Liebig Leon , Koukourakis Nektarios , Czarske Juergen W.
Published: August 2024

Brillouin microscopy has become an important tool for investigating the mechanical properties of tissue. The recently developed Impulsive stimulated Brillouin Scattering (ISBS) promises a label-free, non-invasive measurements of viscoelastic properties of transparent samples and offers the potential for a high temporal resolution. However, the spatial resolution of ISBS is currently limited, which hinders its transfer to real-world applications. Increasing the spatial resolution of ISBS leads to an increase in the energy density of the pump beams, which requires a balancing of the excitation parameters to stay below the phototoxic threshold. This paper focuses on the influences of different excitation parameters on the spatial, temporal and spectral resolution and their optimal values. Combined with the adoption of a noise suppressing window function, a measurement rate of 20µs/pixel in hydrogel is achieved, which is promising for fast 3D imaging. The presented advanced impulsive stimulated Brillouin microscopy can be applied for fast tissue elastography to-ward disease studies.
Deep learning–based automated prediction of mouse seminiferous tubule stage by using bright-field microscopy
Authors: Tokuoka Yuta , Endo Tsutomu , Morikura Takashi , Hiradate Yuki , Ikawa Masahito , Funahashi Akira
Published: August 2024

Infertility is a global issue, with approximately 50% of cases attributed to defective spermatogenesis. For studies into spermatogenesis and spermatogenic dysfunction, evaluating the seminiferous tubule stage is essential. However, the current method of evaluation involves labor-intensive and time-consuming manual tasks such as staining, observation, and image analysis. Lack of reproducibility is also a problem owing to the subjective nature of visual evaluation by experts. In this study, we propose a deep learning–based method for automatically and objectively evaluating the seminiferous tubule stage. Our approach automatically predicts which of 12 seminiferous tubule stages is represented in bright-field microscopic images of mouse seminiferous tubules stained by hematoxylin-PAS. For training and validation of our model, we created a dataset of 1229 tissue images, each labeled with one of 12 distinct seminiferous tubule stages. The maximum prediction accuracy was 79.58% which rose to 98.33% with allowance for a prediction error of ±1 stage. Remarkably, although the model was not explicitly trained on the patterns of transition between stages, it inferred characteristic structural patterns involved in the process of spermatogenesis. This method not only advances our understanding of spermatogenesis but also holds promise for improving the automated diagnosis of infertility.
Cortisol dynamics and GR-dependent feedback regulation in zebrafish larvae exposed to repeated stress
Authors: Castillo-Ramírez Luis A. , Ryu Soojin , De Marco Rodrigo J.
Published: August 2024

Zebrafish larvae show a rapid increase in cortisol in response to acute stressors, followed by a decline. While these responses are documented, both the duration of the refractory period to repeated stressors and the role of glucocorticoid receptors (GR) in specific phases of the glucocorticoid negative feedback are still being clarified. We explored these questions using water vortices as stressors, combined with GR blockage and measurements of whole-body cortisol in zebrafish larvae subjected to single and repeated stress protocols. Cortisol levels were elevated 10 minutes after stress onset and returned to baseline within 30-40 minutes, depending on the stressor strength. In response to homotypic stress, cortisol levels rose above baseline if the second stressor occurred 60 or 120 minutes after the first, but not with a 30-minute interval. This suggests a rapid cortisol-mediated feedback loop with a refractory period of at least 30 minutes. Treatment with a GR blocker delayed the return to baseline and suppressed the refractory period, indicating GR-dependent early-phase feedback regulation. These findings are consistent with mammalian models and provide a framework for further analyses of early-life cortisol responses and feedback in zebrafish larvae, ideal for non-invasive imaging and high-throughput screening.

Summary statement

This study investigates cortisol responses in zebrafish larvae to acute stress, revealing a rapid feedback loop and the glucocorticoid receptor’s role, offering insights for future research in stress biology.
On the rate-limiting dynamics of force development in muscle
Authors: van der Zee Tim J. , Wong Jeremy D. , Kuo Arthur D.
Published: August 2024

Skeletal muscles produce forces relatively slowly compared to the action potentials that excite them. The dynamics of force production are governed by multiple processes, such as calcium activation, cycling of crossbridges between myofilaments, and contraction against elastic tissues and the body. These processes have been included piecemeal in some muscle models, but not integrated to reveal which are the most rate limiting. We therefore examined their integrative contributions to force development in two conventional types of muscle models—Hill-type and crossbridge. We found that no combination of these processes can self-consistently reproduce classic data such as twitch and tetanus. Rather, additional dynamics are needed following calcium activation and facilitating crossbridge cycling, such as for cooperative myofilament interaction and reconfiguration. We provisionally lump such processes into a simple first-order model of “force facilitation dynamics” that integrate into a crossbridge-type muscle model. The proposed model self-consistently reproduces force development for a range of excitations including twitch and tetanus and electromyography-to-force curves. The model’s step response reveals relatively small timing contributions of calcium activation (3%), crossbridge cycling (3%), and contraction (27%) to overall force development of human quadriceps, with a remainder (67%) explained by force facilitation. The same set of model parameters predicts the change in force magnitude (gain) and timing (phase delay) as a function of excitatory firing rate, or as a function of cyclic contraction frequency. Although experiments are necessary to reveal the dynamics of muscle, integrative models are useful for identifying the main rate-limiting processes.

Summary statement

Muscles produce forces relatively slowly, not explained by conventional muscle processes. Quantitative modeling suggests that an intermediate process facilitating force development may be rate limiting.
scACCorDiON: A clustering approach for explainable patient level cell cell communication graph analysis
Authors: Nagai James S. , Schaub Michael T. , G.Costa Ivan
Published: August 2024

Motivation

The combination of single-cell sequencing with ligand-receptor analysis paves the way for the characterization of cell communication events in complex tissues. In particular, directed weighted graphs stand out as a natural representation of cell-cell communication events. However, current computational methods cannot analyze sample-specific cell-cell communication events, as measured in single-cell data produced in large patient cohorts. Cohort-based cell-cell communication analysis presents many challenges, such as the non-linear nature of cell-cell communication and the high variability presented by the patient-specific single-cell RNAseq datasets.

Results

Here, we present scACCorDiON (single-cell Analysis of Cell-Cell Communication in Disease clusters using Optimal transport in Directed Networks), an optimal transport algorithm exploring node distances on the Markov Chain as the ground metric between directed weighted graphs. Additionally, we derive ak-barycenter algorithm using the Wasserstein-based distance, which is able to cluster directed weighted graphs. We compare our approach with competing methods in several large cohorts of scRNA-seq data. Our results show that scACCorDiON can predict clusters better, matching the disease status of samples. Moreover, we show that barycenters provide a robust and explainable representation of cell cell communication events related to the detected clusters. We also provide a case study of pancreas adenocarcinoma, where scACCorDion detects a sub-cluster of disease samples associated with changes in the tumor microenvironment.

Availability

The code of scACCorDiON is available athttps://scaccordion.readthedocs.io/en/latest

Contact

ivan.costa@rwth-aachen.de
Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: model validation and behavioral effects
Authors: Wen Tong Chun , Corkrum Michelle , Carmel Jason B.
Published: August 2024

Unilateral brain injury in neonates results in largely contralateral hand function in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To validate that the sensory tract injury impairs dexterity, we modeled the most common site of sensory tract injury in neonates by targeting the thalamocortical tract. In the postnatal day 7 rats, we used three types of lesions to the thalamocortical tract: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the thalamocortical tract, while sparing the adjacent corticospinal tract in the internal capsule. To measure the impact on dexterity, the cylinder exploration and pasta handling tests were used to test the changes of forelimb use at 8 weeks after injury when the rats reached maturity. Lesions to the thalamocortical tract were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury. Overall, specific sensory system lesions of the thalamocortical tract impair forelimb use, suggesting a key role for skilled movement.
Stability of cross-sensory input to primary somatosensory cortex across experience
Authors: Kato Daniel D , Bruno Randy M
Published: August 2024

Merging information from across sensory modalities is key to forming robust, disambiguated percepts of the world, yet how the brain achieves this feat remains unclear. Recent observations of cross-modal influences in primary sensory cortical areas have suggested that multisensory integration may occur in the earliest stages of cortical processing, but the role of these responses is still poorly understood. We address these questions by testing several hypotheses about the possible functions served by auditory influences on the barrel field of mouse primary somatosensory cortex (S1) usingin vivo2-photon calcium imaging. We observed sound-evoked spiking activity in a small fraction of cells overall, and moreover that this sparse activity was insufficient to encode auditory stimulus identity; few cells responded preferentially to one sound or another, and a linear classifier trained to decode auditory stimuli from population activity performed barely above chance. Moreover S1 did not encode information about specific audio-tactile feature conjunctions that we tested. Our ability to decode auditory audio-tactile stimuli from neural activity remained unchanged after both passive experience and reinforcement. Collectively, these results suggest that while a primary sensory cortex is highly plastic with regard to its own modality, the influence of other modalities are remarkably stable and play a largely stimulus-non-specific role.