bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing neurofibromatosis type I and vision impairment in a resource-limited setting: a case study and multidisciplinary approach
Authors: Adhikari Pratik , Bhujel Nabin
Published: August 2024

Background:

Neurofibromatosis type I (NF1) is a genetic disorder characterized by the development of multiple benign tumors along nerves in the skin, brain, and other parts of the body. It is associated with a range of clinical manifestations, including skin lesions, neurofibromas, and ocular abnormalities, which can significantly impact a patient’s quality of life. Management of NF1 is particularly challenging in resource-limited settings due to limited access to diagnostic and therapeutic resources.

Clinical presentation:

A 62-year-old woman with a known history of NF1 presented with progressive visual impairment. Her condition began in childhood with multiple hyperpigmented skin macules, which developed into numerous cutaneous tumors over time. Examination revealed numerous neurofibromas, café-au-lait spots, and axillary freckling. Significant visual impairment was caused by large fibromas on her eyelids. Histological analysis confirmed benign nerve tissue tumors.

Clinical discussion:

The management strategy in this resource-limited setting focused on regular monitoring, patient education, symptomatic treatment, and multidisciplinary care. Despite the limitations, the patient’s condition was managed effectively through these adapted strategies. The importance of genetic testing for confirmation and further management was noted but not performed due to resource constraints.

Conclusion:

This case highlights the complexities of managing NF1 in resource-limited settings, emphasizing the need for adaptable management approaches. Multidisciplinary care and patient education were crucial in improving the patient’s quality of life. This case underscores the importance of early diagnosis and intervention to prevent complications like visual impairment.
Urachal carcinoma initially presenting only as a liver metastasis, a diagnostic and therapeutic challenge: first case in literature
Authors: Bashour George , Hneino George , Zaher Zain Aldin , Dway Ali , Michael Georges , Alshehabi Zuheir
Published: August 2024

Introduction:

Urachal carcinomas are uncommon malignant neoplasms comprising only 0.01% of all adult cancers. Most patients were aged from 58 to 64 years at diagnosis with 60 years being the median. It usually metastasizes to the lungs (22%), bones (22%), and liver (16%).

Presentation:

We report a case of a 71-year-old female patient who initially presented with two large liver masses and a small nodule on the anterior side of the bladder. The symptoms were nonspecific with abdominal discomfort. The final diagnosis of urachal adenocarcinoma was finalized with a biopsy of the bladder mass. The patient initially received six doses of FOLFOX6 without improvement and then Gem-Carbo, showing improvement after six doses. Finally, the patient received two doses of FOLFIRI-B with no response and kept deteriorating and died after 19 months of treatment.

Discussion:

About 90% of patients are symptomatic and hematuria is the most typical presenting symptom at diagnosis. The low incidence and the histopathologic similarities to adenocarcinoma from various sources pose a difficulty in recognizing the tumor. Our study presents the only case of a urachal carcinoma first manifesting with abdominal mass resulting from liver metastasis with no prior symptoms of urological origins. Also, our study presents the first attempt of using FLOFIRI-B to treat metastatic UraC.

Conclusion:

This case highlights the necessity for clinicopathological correlation to make the correct diagnosis and the challenges in the treatment which urges the need for further research to identify more effective treatment strategies for this rare cancer.
Optimizing the methodology for the assessment of bulbar conjunctival lissamine green staining
Authors: Ghorbani-Mojarrad Neema , Vianya-Estopa Marta , Martin Eilidh , Sweeney Laura E. , Terry Louise , Huntjens Byki , Wolffsohn James S. ,   on behalf of the BUCCLE Research Group
Published: August 2024

SIGNIFICANCE

When using lissamine green for bulbar conjunctival evaluation, the most staining was observed with two applications of the same strip in the same eye, wetted with a drop of saline. The first application was 5 seconds after wetting the strip, and the second was 1 minute later, followed by immediate viewing. This suggests that bulbar staining should be viewed before the lid wiper region.

PURPOSE

This study aimed to optimize the assessment of lissamine green staining of the bulbar conjunctiva by investigating the application technique and subsequent observation period.

METHODS

Twenty-two participants with dry eye (as defined by the Tear Film and Ocular Surface Society Dry Eye Workshop II) were recruited to trial five application methods in randomized order: (1) application immediately after wetting a single strip, (2) application 5 seconds after wetting a single strip, (3) application 10 seconds after wetting a single strip, (4) consecutive single application of sodium fluorescein followed by lissamine green 5 seconds after wetting, and (5) two applications using the same lissamine green strip 5 seconds after wetting, 1 minute apart. Slit-lamp photography of the conjunctiva was performed immediately following application and at 30, 60, 90, and 300 seconds after application. Three experienced (masked) practitioners independently quantified the visible punctate spots and graded the staining intensity within the images in a random order.

RESULTS

Values for punctate spot count (F = 6.29, p<0.0001) and lissamine green staining intensity (F = 6.29, p<0.0001) varied significantly between the different application methods. Using two applications of the same lissamine green strip, 1 minute apart, in the same eye resulted in the greatest values for both punctate spot count and lissamine green staining intensity. Lissamine green staining decreased with time for both spot count (F = 18.87, p<0.0001) and lissamine green staining intensity (F = 11.33, p<0.0001), with the most staining found immediately after application followed by a gradual decline. There was no evidence of any interaction effect between time and application method for either measure (p>0.05 for both).

CONCLUSIONS

The optimal approach for assessing bulbar conjunctival lissamine green staining involves two applications of a whole infused drop resting on the same strip for 5 seconds, applied 1 minute apart. The ocular surface should be viewed immediately after application to maximize the conjunctival staining observed.
Fatal Moans and Bones in Crohn's
Authors: Opara Joyce , Jarrell Heather , Jackson Nicole R.
Published: August 2024

Heterotopic mesenteric ossification (HMO) represents a rare reactive condition characterized by abnormal bone formation within the mesentery. HMO's etiology remains enigmatic, with proposed triggers including trauma-induced metaplasia or bone fragment dislodgment from other sites during abdominal surgery. With fewer than 100 documented cases in the literature, much about this condition remains unknown. In this report, we present a notable case of HMO in a 43-year-old man with a history of severe Crohn's disease and multiple abdominal surgeries. Following a period of unresponsiveness at home, he was admitted to the intensive care unit, where he received palliative care due to a poor prognosis. An autopsy revealed mature, benign bone fragments within the mesentery, alongside severe dehydration, likely exacerbated by decreased oral intake and medication cessation related to his ostomy. Although antemortem imaging revealed HMO, it was misattributed to contrast versus calcification. This case underscores the importance of clinician awareness regarding HMO, particularly its potential implications in inflammatory bowel disease. Early recognition and interdisciplinary collaboration among radiologists, pathologists, and clinicians are paramount in optimizing patient outcomes. Further research is warranted to elucidate this intriguing pathology's pathogenesis and best management strategies.
Extracorporeal Cardiopulmonary Resuscitation Use Among Children With Cardiac Disease in the ICU: A Meta-Analysis and Meta-Regression of Data Through March 2024
Authors: Sperotto Francesca , Daverio Marco , Amigoni Angela , Gregori Dario , Dorste Anna , Kobayashi Ryan L. , Thiagarajan Ravi R. , Maschietto Nicola , Alexander Peta M.
Published: August 2024

OBJECTIVE:

Epidemiologic data on extracorporeal cardiopulmonary resuscitation (ECPR) use in children with cardiac disease after in-hospital cardiac arrest (IHCA) are lacking. We aimed to investigate trends in ECPR use over time in critically ill children with cardiac disease.

DATA SOURCES:

We performed a secondary analysis of a recent systematic review (PROSPERO CRD42020156247) to investigate trends in ECPR use in children with cardiac disease. PubMed, Web of Science, Embase, and Cumulative Index to Nursing and Allied Health Literature were screened (inception to September 2021). For completeness of this secondary analysis, PubMed was also rescreened (September 2021 to March 2024).

STUDY SELECTION:

Observational studies including epidemiologic data on ECPR use in children with cardiac disease admitted to an ICU.

DATA EXTRACTION:

Data were extracted by two independent investigators. The risk of bias was assessed using the National Heart Lung and Blood Institutes Quality Assessment Tools. Random-effects meta-analysis was used to compute a pooled proportion of subjects undergoing ECPR; meta-regression was used to assess trends in ECPR use over time.

DATA SYNTHESIS:

Of the 2664 studies identified, 9 (17,669 patients) included data on ECPR use in children with cardiac disease. Eight were cohort studies, 1 was a case-control, 8 were retrospective, 1 was prospective, 6 were single-center, and 3 were multicenter. Seven studies were included in the meta-analysis; all were judged of good quality. By meta-analysis, we found that a pooled proportion of 21% (95% CI, 15–29%) of pediatric patients with cardiac disease experiencing IHCA were supported with ECPR. By meta-regression adjusted for category of patients (surgical vs. general cardiac), we found that the use of ECPR in critically ill children with cardiac disease significantly increased over time (p = 0.026).

CONCLUSIONS:

About one-fifth of critically ill pediatric cardiac patients experiencing IHCA were supported with ECPR, and its use significantly increased over time. This may partially explain the increased trends in survival demonstrated for this population.
A Comparison of Telesimulation Using the Virtual Resus Room and In Situ Simulation in Pediatric Emergency Medicine
Authors: Hrdy Michael , Faig Walter , Ren Dennis , Lee Brian , Tay Khoon-Yen , Guttadauria Brittany , Zaveri Pavan , Lavoie Megan , Zhao Xian
Published: August 2024

Objectives

During the COVID-19 pandemic, there was a marked shift toward telesimulation in medical education. Limited studies exist comparing the effectiveness of online and offline simulation education. The goals of this study are to evaluate active learners' perceived effectiveness of telesimulation versus in situ simulation and to identify potential shortcomings of existing online teaching platforms.

Methods

Through participant evaluations after a simulation, we compared telesimulation using the Virtual Resus Room (VRR) to in situ simulation in the domains of (1) self-efficacy, (2) fidelity, (3) educational value, and (4) teaching quality. Study subjects included medical and pharmacy residents and medical students completing their pediatric emergency medicine rotation at two children's hospitals as well as nurses, nurse practitioners, and physician assistants who were recently hired and orienting to their new roles in the emergency department. Learners used a modified Michigan Standard Simulation Experience Scale to evaluate either a telesimulation or in situ simulation case. Survey responses were compared using Wilcoxon rank sum tests with Bonferroni correction for multiple comparisons.

Results

In overall assessment, in situ simulation was rated higher than telesimulation. There were significant differences noted related to perceived realism, utility in training device-related skills, and utility in training team-building skills. All P values were less than 0.0036. There were no significant differences between simulation types in perception of physical examination fidelity, instructor adequacy, or self-efficacy.

Conclusions

Telesimulation using the VRR is comparable to in situ simulation in learners' perception of improvement in self-efficacy and of teaching quality for pediatric emergency medicine topics. However, participants felt less able to practice tactile and communication skills virtually. Further innovation is needed to improve learners' experience with fidelity and educational value.
Septal Extension Spreader Graft Combined With Warped Alar Batten Graft for Improvement of Nasal Tip and Alar Asymmetry in Adult Cleft Lip Nasal Deformity
Authors: Quan Xin , Zhang Yanqun , Zhang Xi , Liu Hengxin , Wang Na , Zeng Xianhui , Wei Siming , Dong Chen , Song Baoqiang , Xiao Bo
Published: August 2024

This paper presents the findings of an observational study involving 38 patients to evaluate the application of a surgical technique utilizing an autologous costal cartilage scaffold for correcting nasal tip and alar asymmetry in unilateral cleft lip-nasal deformity. Nasal septum extension spreader grafts (SEG) and warped alar batten grafts, both made from autologous costal cartilage, were utilized in open rhinoplasty procedures. The warped alar batten graft was fixed to the caudal end of the SEG, with the lower lateral cartilage on the cleft side suspended to the free part of the newly created warped alar batten graft to lift the collapsed nasal alar further. Measurements of nasal tip height, nostril height, and the intersection angle of the nasal sill and alar (α) were taken before and after surgery, comparing the ratios between the normal and cleft sides. Patients were followed up for 2.5 to 5.5 years, with all cases showing successful healing and no complications. Postoperative improvements in nasal tip and nostril asymmetries were significant, with statistically significant changes observed in nasal tip height, nostril height, and the intersection angle of nasal sill and alar (α) (P<0.05). The combined use of SEG and warped alar batten graft, both crafted from autologous costal cartilage, effectively corrected nasal tip and alar asymmetry in adult cleft lip nasal deformity cases.
Ommaya Reservoir–Assisted Treatment for Giant Cystic Solid Craniopharyngioma in Children
Authors: Shao Qiang , Xiao Kai , Xu Hao , Hu Fei , Pan Li , Chen Yang , Zhang Yang Ming , Chen Lang
Published: August 2024

Objective:

In children with giant cystic solid craniopharyngioma (CP), the Ommaya reservoir was implanted in the CP cavity, and the cystic fluid was continuously drained for 5 days before the tumor resection.

Methods:

An 11-year-old male patient was admitted to the hospital due to vision loss for 1 year, intermittent headache, vomiting for 6 months, and frequent urination for 2 months. Besides, magnetic resonance imaging of the head showed cystic solid lesions in the sellar region, suprasellar, and bilateral frontal lobes, with a size of 96.0×82.6×76.0 mm. Before the surgical resection, an Ommaya reservoir was implanted within the tumor cavity. The drainage was continued for 5 days and was 39 to 50 mL (43.80 ± 4.67 mL). Following the tumor shrank, a craniotomy was performed.

Results:

Following surgical treatment, the CP was entirely removed. The child subsequently developed hypothyroidism and hypocortisolism, for which hormone replacement therapy was administered. No tumor recurrence was observed after 3 years of follow-up.

Conclusion:

The treatment of giant cystic solid CP in children is challenging. Preoperative implantation of the Ommaya reservoir, continuous drainage of cystic fluid, shrinkage of the tumor, and reduction of tumor tension are beneficial for tumor resection.
Noninvasive Evaluation of Acupuncture-Induced Cortical Plasticity in Advanced Rehabilitation of Facial Paralysis
Authors: Yu Li-qing , Ma Hao , Cao Lian-ying , Zhou Yu-lu
Published: August 2024

Objective:

Facial paralysis (FP), which resulted from head and neck cancer resection, significantly impacts patients’ quality of life. Traditional assessments rely on subjective evaluations and electromyography, whereas functional magnetic resonance imaging offers a noninvasive alternative for enhanced rehabilitation. Acupuncture has shown promise in promoting cerebral cortex reorganization, yet the precise relationship between acupuncture-induced structural and functional changes remains unclear, necessitating further investigation into therapeutic mechanisms.

Methods:

Fifty-five patients afflicted with FP underwent evaluations using voxel-mirrored homotopic connectivity (VMHC) and tract-based spatial statistics and were divided into the acupuncture intervention group (n = 35) and pseudo intervention group (n = 20). Comparative analyses of metrics pre and postintervention were conducted to delineate therapy-induced modifications in acupuncture intervention. The postacupuncture effect between groups to verify the necessity of accurate positioning for the rehabilitation of FP.

Results:

Patients with FP showed deficits in VMHC in regions of the postcentral, precentral, and parietal areas. Corpus callosum and internal capsule showed significantly increased fractional anisotropy of the white matter skeleton in tract-based spatial statistics after treatment. Comparison postintervention results between groups exhibited deficits in VMHC and increased fractional anisotropy in regions of the corpus callosum in the acupuncture intervention group.

Conclusions:

Early acupuncture intervention may suppress cortical hyperactivation and restore interhemispheric inhibition across the corpus callosum to inhibit maladaptive structural plasticity. Precise acupoint localization is crucial for effective therapy, highlighting the potential of postacupuncture cortical space data for refining therapeutic strategies.
Diagnosis and Treatment of an Unusual Maxillary Gingiva Malignant Melanoma Arising Around Dental Implant
Authors: Paka Lubamba Grace , Hua Yufei , Zhang Gaowei , Bao Mingzhe , Zhao Guile , Zhang Zhuoyuan , Wang Guanru , Gao Ning , Zhu Guiquan , Li Chunjie
Published: August 2024

Background:

Oral mucosal malignant melanoma (OMMM) arises from malignant melanocytes, and the most affected age, sex, and site are 20 to 83 years, male, and the mucosa of hard palate and maxillary gingiva, respectively. Despite several cases of OMMM have been published in the literature, cases of malignant melanoma arising around the dental implant are rarely reported.

Case Summary:

A 59-year-old male was admitted to our Department with the complain of gingival black pigmentations following dental implant treatment for 3 years. Intraoral examination revealed a painless black lobulated mass around maxillary gingiva and alveolar fossa of dental implant (first molar). CBCT revealed bone destruction around the implant. Positron emission tomography/computed tomography confirmed the presence of tumoral lesion, which was diagnosed as right maxillary gingiva malignant melanoma (T4aN0M0). Partial maxillectomy+buccal fat pad transfer+free tissue patch repair were carried out. Pathologic analyses confirmed the diagnosis of malignant melanoma. The postoperative course was uneventfully, the patient is undergoing follow-up without any evidence of recurrence.

Conclusion:

Our report showed that an ill-fitting dental implant may cause OMMM. Excisional biopsy with sufficient surgical margins allows complete removal and final diagnosis of OMMM. Early diagnosis and treatment are recommended.
Atypical Presentation of Hypothenar Hammer Syndrome
Authors: Yang Lydia , Al-Hayek Shady
Published: August 2024

Hypothenar hammer syndrome (HHS) is a rare vascular disease caused by repetitive trauma to the hypothenar eminence, leading to thrombi and sometimes aneurysm development in the ulnar artery. This case report presents an atypical presentation of HHS with pathology extending distally into the digital arteries, complicated by an unclear history and unique genetic contributions. The patient, a 58-year-old male with a distant history of jackhammer work, presented with progressive pain in his fourth and fifth digits. CT angiography revealed patchy vascular lesions in the palmar arch. He developed another thrombi despite being treated initially with heparin. Genetic analysis revealed that he was heterozygous for Factor V Leiden with decreased protein C levels. Following surgical intervention, he recovered well. The author report a case of HHS in which medical management was superior to surgical treatment due to combined occupational and genetic predisposition for vascular pathology with findings extending beyond the ulnar artery.
Anxiety and Work Disability in Patients With Immune-Mediated Inflammatory Diseases
Authors: Marcon Thomas , Lorenzon Greta , Zanotti Renzo , Danielis Matteo
Published: August 2024

Immune-mediated inflammatory diseases (IMIDs) are chronic diseases that are associated with an inflammatory process with unclear etiology and occur in genetically predisposed individuals. In this study, inflammatory bowel disease (IBD) and rheumatic disease (RD) were examined. The aim of the research is to evaluate the relationship between IMID and state anxiety and work impairment in patients. A cross-sectional study was conducted in an outpatient clinic for rheumatology and gastroenterology at an Italian university hospital. A total of 476 patients (261 IBD and 215 RD) were considered. Patients diagnosed with IBD demonstrated significantly higher levels of anxiety, encompassing both trait and state anxiety, compared to those with RD (p < .001). While trait anxiety exhibited a modest positive correlation with work productivity loss (r = .163; p = .046), activity impairment showed a positive correlation with both state anxiety (r = .243; p < .001) and trait anxiety (r = .206; p = .002). The impact of anxiety on job performance and daily activities should not be underestimated, as it may elevate the risk of unemployment and absenteeism and lead to increased societal costs.
THE USE OF POLOXAMER 188 IN BURN INJURY TREATMENT: A SYSTEMATIC LITERATURE REVIEW
Authors: Mutore Kevin T. , Koduri Roopa , Alatrash Nagham , Nomellini Vanessa
Published: August 2024

Although there have been numerous advancements in burn wound management, burn injuries are still a major cause of morbidity and mortality in the United States, and novel therapeutics are still needed to improve outcomes. Poloxamer 188 (P188) is a synthetic copolymer with Food and Drug Administration (FDA) approval that has many biological applications. This study aimed to review the literature on P188 in burn injuries and its effects based on burn mechanisms. We employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to complete this systematic literature review. We searched the databases of Google Scholar, PubMed, and SCOPUS using the keywords burn, p188, poloxamer 188, and pluronic F68 in combination. Two reviewers independently screened the articles for inclusion. Articles that were not in English, were book chapters or conference proceedings, or did not evaluate P188 in the setting of burn injuries were excluded. We included a total of 33 full-text articles with both in vivo and in vitro preclinical studies. P188 was found to be beneficial in animal and cell studies evaluating electrical and thermal burn injuries. P188 was also found to be useful in burn wound management. Although its utility may be limited in radiation injuries, P188 may be helpful in delaying the initial damage caused by radiation burns. P188 therefore has the potential to be used as a therapy in both burn wound management and in the treatment of systemic injuries sustained through burns. Future studies should aim to assess the efficacy of P188 in clinical models of burn injury.
ENDOTHELIAL-DEPENDENT VASCULAR REACTIVITY AFTER CARDIOPULMONARY BYPASS IS ASSOCIATED WITH UNIQUE METABOLOMIC SIGNATURES
Authors: Stark Ryan J. , Schrimpe-Rutledge Alexandra C. , Codreanu Simona G. , Sherrod Stacy D. , McLean John A. , Krispinsky Luke T. , Lamb Fred S.
Published: August 2024

Cardiopulmonary bypass (CPB), an extracorporeal method necessary for the surgical correction of complex congenital heart defects, incites significant inflammation that affects vascular function. These changes are associated with alterations in cellular metabolism that promote energy production to deal with this stress. Utilizing laser Doppler perfusion monitoring coupled with iontophoresis in patients undergoing corrective heart surgery, we hypothesized that temporal, untargeted metabolomics could be performed to assess the link between metabolism and vascular function. Globally, we found 2,404 unique features in the plasma of patients undergoing CPB. Metabolites related to arginine biosynthesis were the most altered by CPB. Correlation of metabolic profiles with endothelial-dependent (acetylcholine [ACh]) or endothelial-independent (sodium nitroprusside [SNP]) vascular reactivity identified purine metabolism being most consistently associated with either vascular response. Concerning ACh-mediated responses, acetylcarnitine levels were most strongly associated, while glutamine levels were associated with both ACh and SNP responsiveness. These data provide insight into the metabolic landscape of children undergoing CPB for corrective heart surgery and provide detail into how these metabolites relate to physiological aberrations in vascular function.
A NOVEL OPSONIC EXTRACELLULAR CIRP INHIBITOR MOP3 ALLEVIATES GUT ISCHEMIA/REPERFUSION INJURY
Authors: Hollis Russell , Li Jingsong , Lee Yongchan , Jin Hui , Zhou Mian , Nofi Colleen P. , Sfakianos Maria , Coppa Gene , Aziz Monowar , Wang Ping
Published: August 2024

Introduction: Gut ischemia and reperfusion (I/R) injury promotes the release of damage-associated molecular patterns (DAMPs) such as extracellular cold-inducible RNA-binding protein (eCIRP). Gut I/R often leads to acute lung injury (ALI), a major contributor to mortality. Milk fat globule-epidermal growth factor–factor VIII–derived oligopeptide-3 (MOP3) is a novel peptide that attenuates sepsis by opsonizing eCIRP and facilitating its phagocytic clearance. We hypothesized that MOP3 reduces inflammation, mitigates gut and lung injury, and improves survival in gut I/R injury. Methods: Phagocytosis of FITC-labeled eCIRP by intestinal epithelial cells was determined by confocal microscopy, and the cell supernatant was evaluated for cytokine expression by ELISA. Adult C57BL/6 mice underwent 60 min of gut ischemia via superior mesenteric artery occlusion followed by reperfusion. Mice were treated with MOP3 or vehicle via retro-orbital injection at the time of reperfusion. At 4 h post-I/R, blood, gut, and lungs were harvested for further assay. In additional mice, 36-h survival was assessed. Plasma levels of injury and inflammatory markers were measured with colorimetry and ELISA, respectively. Tissue mRNA expression was measured with qPCR. Myeloperoxidase (MPO), TUNEL, histologic injury, and ZO-1 immunohistochemistry assessments were performed. Results: MOP3 significantly increased eCIRP phagocytosis by intestinal epithelial cells (P < 0.01) and decreased IL-6 release (P < 0.001). Gut I/R caused elevated plasma eCIRP levels. MOP3 treatment significantly reduced plasma levels of IL-1β (P < 0.01), IL-6 (P < 0.05), and lactate dehydrogenase (P < 0.05) along with a significant decrease in gut (P < 0.05) and lung (P < 0.001) injury scores as well as gut cell death (P < 0.05). Moreover, MOP3 reduced pulmonary levels of chemokines and the granulocyte activation marker MPO after gut I/R. Mechanistically, ZO-1 expression in the gut was decreased following gut I/R injury, whereas MOP3 significantly reversed the decrease in ZO-1 mRNA expression (P < 0.001). Finally, mice treated with MOP3 exhibited a significant decrease in mortality (P < 0.05). Conclusions: Treatment with MOP3 effectively mitigates organ injury induced by gut I/R. This beneficial effect is attributed to the facilitation of eCIRP clearance, directing the potential of MOP3 as an innovative therapeutic approach for this critical and often fatal condition.
A single night in hypoxia either with or without ketone ester ingestion reduces sleep quality without impacting next day exercise performance
Authors: Stalmans Myrthe , Tominec Domen , Ruben Robberechts , Lauriks Wout , Ramaekers Monique , Debevec Tadej , Poffé Chiel
Published: August 2024

Background

Sleeping at (simulated) altitude is highly common in athletes as an integral part of altitude training camps or sport competitions. However, it is also often feared due to proclaimed negative effects on sleep quality, thereby potentially hampering exercise recovery and next-day exercise performance. We recently showed that ketone ester (KE) ingestion beneficially impacted sleep following strenuous, late evening exercise in normoxia, and alleviated hypoxemia. Therefore, we hypothesized that KE ingestion may be an effective strategy to attenuate hypox(em)ia-induced sleep dysregulations.

Methods

Eleven healthy, male participants completed three experimental sessions including normoxic training and subsequent sleep in normoxia or at a simulated altitude of 3,000m while receiving either KE or placebo post-exercise and pre-sleep. Sleep was evaluated using polysomnography, while next-day exercise performance was assessed through a 30-min all-out time trial (TT30’). Physiological measurements included oxygen status, heart rate variability, ventilatory parameters, blood acid-base balance and capillary blood gases.

Results

Hypoxia caused a ∼3% drop in sleep efficiency, established through a doubled wakefulness after sleep onset and a ∼22% reduction in slow wave sleep. KE ingestion alleviated the gradual drop in SpO2throughout the first part of the night, but did not alter hypoxia-induced sleep dysregulations. Neither KE, nor nocturnal hypoxia affected TT30’performance, but nocturnal hypoxia hampered heart rate recovery following TT30’.

Conclusion

We observed that sleeping at 3,000m altitude already impairs sleep efficiency. Although this hypoxia-induced sleep disruption was too subtle to limit exercise performance, we for the first time indicate that sleeping at altitude impairs next-day exercise recovery. KE alleviated nocturnal hypoxemia whenever SpO2values dropped below ∼85%, but this did not translate into improved sleep or next-day exercise performance.
Household behaviour change interventions to improve sanitation and hygiene practices in urban settings: a scoping review
Authors: MacLeod Clara , Davies Katherine , Mwenge Mwamba M , Chipungu Jenala , Cumming Oliver , Dreibelbis Robert
Published: August 2024

Introduction

Behaviour change interventions have the potential to improve sanitation and hygiene practices in urban settings. However, the evidence on which behaviour change interventions are effective is unclear. This scoping review assesses the effectiveness of behaviour change interventions on sanitation and hygiene practices in urban settings.

Methods

We performed electronic searches across five databases and one grey literature database to identify relevant studies published between 1 January 1990 and 20 November 2023 in English. Eligible study designs included randomised and non-randomised controlled trials with a concurrent control. Studies were eligible for inclusion if they reported a behaviour change intervention for improving sanitation and/or hygiene practices in an urban setting. Individual behaviour change intervention components were mapped to one of nine intervention functions of the capabilities, opportunities, motivations, and behaviour (COM-B) framework. Risk of bias was assessed for each study using an adapted Newcastle-Ottawa scale.

Results

After de-duplication, 8,249 documents were screened by abstract and title, with 79 documents retrieved for full-text screening. We included 13 studies ranging from low- to high-quality. The behaviour change interventions had mixed effects on sanitation and hygiene practices in urban settings. Specifically, interventions improved latrine quality but not safe child faeces disposal. Interventions often improved handwashing with soap at key times and sometimes increased the presence of soap and water at the handwashing facility. There is limited evidence on the effect on food hygiene practices. Most study outcomes were measured between 6 and 12 months after intervention implementation, which may undermine the sustainability of behaviour change interventions.

Conclusion

Despite mixed effects on sanitation and hygiene outcomes, behaviour change interventions can improve certain practices in urban settings, such as latrine quality improvements and handwashing with soap at the household or compound level. More ambitious behaviour change interventions are needed to reduce disparities in sanitation and hygiene access in urban areas globally.
ERH regulates type II interferon immune signaling through post-transcriptional regulation ofJAK2mRNA
Authors: Soderholm Adrian , Vunjak Milica , De Almeida Melanie , Popitsch Niko , Podvalnaya Nadezda , Araguas-Rodriguez Pablo , Scinicariello Sara , Nischwitz Emily , Butter Falk , Ketting René , Ameres Stefan L. , Müller-McNicoll Michaela , Zuber Johannes , Versteeg Gijs A.
Published: August 2024

Type II interferon (IFNγ) signaling is essential for innate immunity and critical for effective immunological checkpoint blockade in cancer immunotherapy. Genetic screen identification of post-transcriptional regulators of this pathway has been challenging since such factors are often essential for cell viability. Here, we utilize our inducible CRISPR/Cas9 approach to screen for key post-transcriptional regulators of IFNγ signaling, and in this way identify ERH and the ERH-associated splicing and RNA export factors MAGOH, SRSF1, and ALYREF. Loss of these factors impairs post-transcriptional mRNA maturation ofJAK2, a crucial kinase for IFNγ signaling, resulting in abrogated JAK2 protein levels and diminished IFNγ signaling. Further analysis highlights a critical role for ERH in preventing intron retention in AU-rich regions in specific transcripts, such asJAK2. This regulation is markedly different from previously described retention of GC-rich introns. Overall, these findings reveal that post-transcriptionalJAK2processing is a critical rate-limiting step for the IFNγ-driven innate immune response.
Cycling DOF Factor mediated seasonal regulation of sexual reproduction and cold response is not conserved inPhyscomitrium patens
Authors: Freidinger Alexander G. , Woodward Lauren A. , Bùi Jo Trang , Doty Gillian , Ruiz Shawn , Conant Erika , Hicks Karen A.
Published: August 2024

Many land plants have evolved such that the transition from vegetative to reproductive development is synchronized with environmental cues. Examples of reproduction in response to seasonal cues can be found in both vascular and nonvascular species; however, most of our understanding of the molecular events controlling this timing has been worked out in angiosperm model systems. While the organism-level mechanisms of sexual reproduction vary dramatically between vascular and nonvascular plants, phylogenetic and transcriptomic evidence suggest paralogs in nonvascular plants may have conserved function with their vascular counterparts (Holm et al. 2010; Zhao et al. 2019; Genau et al. 2021). Given thatPhyscomitrium patensundergoes sexual reproductive development in response to photoperiodic and cold temperature cues (Hohe et al. 2002), it is well-suited for studying evolutionarily conserved mechanisms of seasonal control of reproduction. Thus, we used publicly available microarray data to identify genes differentially expressed in response to temperature cues (Fernandez-Pozo et al. 2020). We identified twoCDF-like(CDL) genes in theP. patensgenome that are the most like the angiospermArabidopsis thalianaCDFs based on conservation of protein motifs and diurnal expression patterns. In angiosperms, DNA-One Finger Transcription Factors (DOFs) play an important role in regulating photoperiodic flowering, regulating physiological changes in response to seasonal temperature changes, and mediating the cold stress response (Imaizumi et al. 2005; Kloosterman et al. 2013; Fornara et al. 2015; Ridge et al. 2016; Ding et al. 2018; Blair et al. 2022). We created knockout mutations and tested their impact on sexual reproduction and response to cold stress. Unexpectedly, the timing of sexual reproduction in theppcdldouble mutants did not differ significantly from wild type, suggesting that thePpCDLsare not necessary for seasonal regulation of this developmental transition. We also found that there was no change in expression of downstream cold-regulated genes in response to cold stress and no change in freezing tolerance in the knockout mutant plants. Finally, we observed no interaction between PpCDLs and the partial homologs of FKF1, anArabidopsis thalianarepressor of CDFs. This is different from what is observed in angiosperms (Fornara et al. 2009; Corrales et al. 2014; Song et al. 2016, Li et al. 2013; Han et al. 2015, Wang et al. 2023, Li et al. 2009), which suggests that the functions of CDF proteins in angiosperms are not conserved inP. patens.
Lipid- and protein-directed photosensitizer proximity labeling captures the cholesterol interactome
Authors: Becker Andrew P. , Biletch Elijah , Kennelly John Paul , Julio Ashley R. , Villaneuva Miranda , Nagari Rohith T. , Turner Daniel W. , Burton Nikolas R. , Fukuta Tomoyuki , Cui Liujuan , Xiao Xu , Hong Soon-Gook , Mack Julia J. , Tontonoz Peter , Backus Keriann M.
Published: August 2024

The physical properties of cellular membranes, including fluidity and function, are influenced by protein and lipid interactions. In situ labeling chemistries, most notably proximity-labeling interactomics are well suited to characterize these dynamic and often fleeting interactions. Established methods require distinct chemistries for proteins and lipids, which limits the scope of such studies. Here we establish a singlet-oxygen-based photocatalytic proximity labeling platform (POCA) that reports intracellular interactomes for both proteins and lipids with tight spatiotemporal resolution using cell-penetrant photosensitizer reagents. Using both physiologically relevant lipoprotein-complexed probe delivery and genetic manipulation of cellular cholesterol handling machinery, cholesterol-directed POCA captured established and unprecedented cholesterol binding proteins, including protein complexes sensitive to intracellular cholesterol levels and proteins uniquely captured by lipoprotein uptake. Protein-directed POCA accurately mapped known intracellular membrane complexes, defined sterol-dependent changes to the non-vesicular cholesterol transport protein interactome, and captured state-dependent changes in the interactome of the cholesterol transport protein Aster-B. More broadly, we find that POCA is a versatile interactomics platform that is straightforward to implement, using the readily available HaloTag system, and fulfills unmet needs in intracellular singlet oxygen-based proximity labeling proteomics. Thus, we expect widespread utility for POCA across a range of interactome applications, spanning imaging to proteomics.
Gut Commensal Bacteria-Derived Methionine is Required for Host Reproduction by Modulating RNA m6A Methylation of the Insulin Receptor
Authors: Zhang Qiuyuan , Deng ZhuRong , Li Xiaoxue , Qiao Jiao , Li Ziniu , Liu Peipei , Handler Alfred M. , Lemaitre Bruno , Zheng Weiwei , Zhang Hongyu
Published: August 2024

Gut commensal bacteria promote host reproduction by modulating metabolism and nutrition, yet the molecular mechanisms by which microbes modulate reproduction remain unclear. Here, we show that gut commensal bacteria promote host reproduction by providing amino-acid methionine, which controls the RNA m6A modification level ofinsulin receptor(InR) in the ovary of the invasive insectBactrocera dorsalis. RNA m6A levels and S-adenosyl-methionine (SAM) titers in the ovaries were sharply reduced in antibiotic treatedB. dorsaliscompared with untreated insects, resulting in arrested ovarian development and decreased fecundity. The intestinal commensal bacteriaEnterobacter hormaecheior theE. hormaechei-derived metabolite methionine restored the decreased RNA m6A level and the reproductive defects. Notably, knockdown ofMETTL3andMETTL14, two genes encoding the RNA m6A methyltransferases, led to a decrease in the mRNA level ofInRand underdevelopment of ovaries inB. dorsalis,and blocked the promoting effect of methionine on ovarian development and fecundity. Collectively, our study identifies an unrecognized role of RNA m6A methylation modification that underlies microbial control of host reproduction. Our findings further expand the functional landscape of m6A modification to include nutrient-dependent control of ovarian development and highlight the essential role of epigenetic regulation in microbe-host interactions.
Harnessing light heterogeneity to optimise controlled environment agriculture
Authors: Claydon Will , Redmond Ethan J. , Vong Gina YW , Kluczkovski Alana , Thomas Alice , Sutton Phoebe , Denby Katherine , Ezer Daphne
Published: August 2024

Yield is impacted by the environmental conditions that plants are exposed to. Controlled environmental agriculture provides growers with an opportunity to fine-tune environmental conditions for optimising yield and crop quality. However, space and time constraints will limit the number of experimental conditions that can be tested, which will in turn limit the resolution to which environmental conditions can be optimised. Here we present an innovative experimental approach that utilises the existing heterogeneity in light quantity and quality across a vertical farm to evaluate hundreds of environmental conditions concurrently. It proposes a three-phase workflow for identifying critical light variables, which can guide targeted improvements in yield and energy use. Using an observational study design, we identify features in light quality that are most predictive of biomass in different microgreens crops (kale, radish and sunflower) that may inform future iterations of lighting technology development for vertical farms. The findings suggest that light quality, rather than just light intensity, plays a crucial role in uniform crop yields and that light sensitivities are variety-specific, highlighting the importance of tailored light recipes for different crops.
Live-tracking of replisomes reveals nutrient-dependent regulation of replication elongation rates inCaulobacter crescentus
Authors: Adhikashreni Inchara S , Joseph Asha Mary , Phadke Sneha , Badrinarayanan Anjana
Published: August 2024

In bacteria, commitment to genome replication (initiation) is intricately linked to nutrient availability. Whether growth conditions affect other stages of replication beyond initiation, remains to be systematically studied. To address this, we assess the replication dynamics ofCaulobacter crescentus, a bacterium that undergoes only single round of replication per cell cycle, by tracking the replisome across various growth phases and nutrient conditions. We find that the replication elongation rates slowdown as cells transition from exponential (high-nutrient) to stationary (low-nutrient) phase, and this contributes significantly to the overall cell cycle delay. While elongation rates are correlated with growth rates, both properties appear to be differentially influenced by nutrient status. This slowdown in replication progression is not associated with increased mutagenesis or upregulation of the DNA damage responses. We conclude that the growth conditions not only dictate the commitment to replication but also the rates of genome duplication. Such regulation appears to be distinct from stress-induced replication slowdown and likely serves as an adaptive mechanism to cope with fluctuations in nutrient availability in the environment.
Analysis of the effects of mating systems on lineage diversification across multiple genera
Authors: Xu Kuangyi
Published: August 2024

The transition from outcrossing to self-fertilization is a major evolutionary trend in plants, with selfing long hypothesized an evolutionary dead end. Recent theories suggest that elevated extinction rates may be restricted to highly selfing rather than mixed-mating populations. Previous analyses of the effects of mating systems on diversification found mixed results, varying by focal clades and potentially suffering from several limitations.

We collected data on three mating-system-related characters. We also collected life form data to indirectly distinguish between mixed mating and highly selfing. We estimated speciation and extinction rates for character states, and state transition rates in 27 genera.

We find that outcrossing lineages diversify at higher rates than selfing lineages, while the impact of mating systems on speciation is not consistent across genera. Among self-compatible lineages, annuals/short-lived exhibit significantly lower diversification rates than perennials. Models incorporating hidden states often provide a better fit than those without.

The results suggest that selfing lineages overall have lower diversification rates. This may be primarily contributed by elevated extinction rates in highly selfing lineages, which may also explain the prevalence of mixed-mating systems. However, the influences of mating systems on diversification may be often driven by other factors correlated with mating system transitions.
Description of Bacterial RNA Transcripts Detected inMycobacterium tuberculosis– Infected Cells from Peripheral Human Granulomas using Single Cell RNA Sequencing
Authors: Moos Philip J. , Carey Allison F. , Joseph Jacklyn , Kialo Stephanie , Norrie Joe , Moyarelce Julie M. , Amof Anthony , Nogua Hans , Lim Albebson L. , Barrows Louis R.
Published: August 2024

Mycobacterium tuberculosis(Mtb) remains a global human health threat and a significant cause of human morbidity and mortality. We document here the capture of Mtb transcripts in libraries designed to amplify eukaryotic mRNA. These reads are often considered spurious or nuisance and are rarely investigated. Because of early literature suggesting the possible presence of polyadenylated transcripts in Mtb RNA, we included the H37Rv Mtb reference genome when assembling scRNA seq libraries from fine needle aspirate samples from patients presenting at the TB clinic, Port Moresby General Hospital, Papua New Guinea. We used 10X Genomics single-cell RNA sequencing transcriptomics pipeline, which initiates mRNA amplification with poly-T primers on ∼30-micron beads designed to capture, in this case, human mRNA associated with individual cells in the clinical samples. Utilizing the 10X Genomics Cell Ranger tool to align sequencing reads, we consistently detected bacterial small and large ribosomal subunit RNA sequences (rrs and rrl, respectively) and other bacterial gene transcripts in the cell culture and patient samples. We interpret Mtb reads associated with the host cell’s unique molecular identifier (UMI) and transcriptome to indicate infection of that individual host cell. The Mtb transcripts detected showed frequent sequence variation from the reference genome, with greater than 90% of the rrs or rrl reads from many clinical samples having at least 1 sequence difference compared to the H37Rv reference genome. The data presented includes only bacterial sequences from patients with TB infections that were confirmed by the hospital pathology lab using acid-fast microscopy and/or GeneXpert analysis. The repeated, non-random nature of the sequence variations detected in Mtb rrs and rrl transcripts from multiple patients, suggests that, even though this appears to be a stochastic process, there is possibly some selective pressure that limits the types and locations of sequence variation allowed. The variation does not appear to be entirely artefactual, and it is hypothesized that it could represent an additional mechanism of adaptation to enhance bacterial fitness against host defenses or chemotherapy.