bluuebunny/crossref_metadata_2025 huggingface dataset:
Circ_0007445 inhibits trophoblast cell proliferation, migration and invasion by mediating the miR-4432/HTRA1 axis in preeclampsia
Authors: Shao Wenjia , Cui Jinquan , Wang Wuliang
Published: May 2024

Background

: Circular RNAs (circRNAs) have been shown to be extensively involved in preeclampsia progression. At present, the role of circ_0007445 in preeclampsia progression is not clear.

Methods:

A total of 30 preeclampsia patients and 30 normal pregnant women were recruited in our study. The function of trophoblast cells was explored to clarify the role and mechanism of circ_0007445 on the preeclampsia progression. The expression of circ_0007445, microRNA (miR)-4432 and high temperature requirement A1 (HTRA1) was analyzed by quantitative real-time PCR. The proliferation, migration and invasion of trophoblast cells were determined by cell counting kit 8 assay, EdU assay, colony formation assay, flow cytometry, and transwell assay. Protein expression was examined by western blot analysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were used to assess RNA interaction relationships.

Results:

Our data suggested that circ_0007445 had increased expression in preeclampsia patients. Knockdown of circ_0007445 enhanced trophoblast cell proliferation, migration and invasion. MiR-4432 was lowly expressed in preeclampsia patients, and it could be sponged by circ_0007445. MiR-4432 inhibitor overturned the promotion effects of circ_0007445 knockdown on trophoblast cell functions. HTRA1 was highly expressed in preeclampsia patients, and it could be targeted by miR-4432. HTRA1 overexpression could also reverse the proliferation, migration and invasion of trophoblast cells promoted by miR-4432 mimic. In addition, circ_0007445 positively regulated HTRA1 through targeting miR-4432.

Conclusion:

:Our results suggested that circ_0007445 facilitated the development of preeclampsia by suppressing trophoblast cell function through miR-4432/HTRA1 axis.
Association between blood pressure variability and risk of kidney function decline in hypertensive patients without chronic kidney disease: a post hoc analysis of Systolic Blood Pressure Intervention Trial study
Authors: Wang Zhiyan , Li Wenjie , Jiang Chao , Wang Jue , Hua Chang , Tang Yangyang , Zhang Hao , Liu Xinru , Wang Yufeng , Gao Mingyang , Lv Qiang , Dong Jianzeng , Ma Changsheng , Du Xin
Published: May 2024

Background:

Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD.

Methods:

A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria.

Results:

A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2–Q4; hazard ratios and 95% confidence interval were 1.81 (1.07–3.04), 1.85 (1.10–3.12) and 1.90 (1.13–3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria (P > 0.05).

Conclusion:

This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups.

Registration:

URL: https://clinicaltrials.gov/, Unique identifier: NCT01206062
Multiple drug intolerance in antihypertensive patients: what is known and what is missing
Authors: Palermiti Alice , Pappaccogli Marco , Rabbia Franco , D’Avolio Antonio , Veglio Franco
Published: May 2024

Drug allergy and intolerance are increasingly recognized as significant public health concerns, leading to adverse reactions in patients undergoing pharmacological treatments. Multiple drug intolerance syndrome (MDIS), characterized by adverse reactions to at least three different drug classes without a clear immunological mechanism, poses a substantial challenge, particularly in hypertensive patients. Despite its link to suboptimal adherence and uncontrolled blood pressure, MDIS in the context of hypertension remains insufficiently explored. This review synthesizes existing literature on MDIS, emphasizing clinical characteristics, pathogenesis, and psychiatric comorbidity. Furthermore, it delves into MDIS in the context of hypertension, highlighting the importance of a multidisciplinary approach in diagnosis and management, including innovative therapeutic strategies such as novel therapeutic algorithms or renal denervation. The review concludes by emphasizing the necessity for further research and clinical trials to enhance our understanding and address MDIS, especially in hypertensive patients.
Maximization of scope of practice and satisfaction among geriatric nurse practitioners in Israel
Authors: Romem Anat , Zalcman Beth G. , Pinchas-Mizrachi Ronit
Published: May 2024

Background:

There is an increasing demand for comprehensive geriatric care. Nurse practitioners (NPs), who undergo specialized training, are situated to provide such care. In Israel, the role of a geriatric nurse practitioner was introduced in the health care system 10 years ago. However, little is known about the rate of professional satisfaction and realization of full potential among these nurses.

Purpose:

The aims of this study are (1) to describe the geriatric NP workforce in Israel, (2) to measure the current geriatric scope of practice, and (3) to measure the geriatric NP satisfaction from their working environment.

Methodology:

For this cross-sectional study, a survey, comprising three sections relating to demographics, professional qualifications and scope of practice, and career satisfaction, was sent to 53 geriatric nurse practitioners in Israel who currently work as geriatric nurse practitioners.

Results:

Forty-seven nurses participated in the survey. Almost 64% reported that they are satisfied with their position, and 72% reported that they are able to fulfill their full scope of practice. The mean score for scope of practice was 68.31 out of a possible score of 100.

Conclusions:

A number of qualifications were correlated with satisfaction at work, indicating that nurses tend to be more satisfied at work when they are able to fulfill their potential.

Implications:

Ensuring nurse practitioners' ability to realize their full potential should be a goal of the health care system. Interventions should be in place to encourage nurses to perform tasks related to their work, for which they are trained.
Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-Center Study
Authors: Sakurai Yukari , Iwasaki Fuminori , Hirose Ayana , Matsumoto Naoya , Miyagawa Naoyuki , Keino Dai , Yokosuka Tomoko , Hamanoue Satoshi , Yanagimachi Masakatsu , Shiomi Masae , Goto Shoko , Tanaka Mio , Tanaka Yukichi , Nozawa Kumiko , Goto Hiroaki
Published: May 2024

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.
Diagnostic Value of the Pediatric Bleeding Questionnaire in Prediction of Bleeding in Minor Surgery
Authors: Çakil Güzin Ayşe , Oymak Yeşim , Oral Akgün , Vergin Canan
Published: May 2024

Objective:

Preoperative coagulation tests have not been shown to be effective in predicting bleeding complications. The Pediatric Bleeding Questionnaire (PBQ) is a proven and sensitive tool for diagnosing children with a predisposition to bleeding. The aim of this study was to evaluate the usefulness of PBQ as a preoperative screening tool for the prediction of bleeding after minor surgical interventions.

Methods:

Preoperative coagulation tests and PBQ were performed in all patients who underwent minor surgery. The postoperative bleeding status was evaluated and then compared with the coagulation tests and PBQ of the patients.

Results:

Evaluation was made of a total of 706 patients, comprising 91.2% males and 8.8% females, with a mean age of 4.8 years (median: 4 y, QR: 1 to 7 y). Prolongation in coagulation tests was observed in 131 (18.5%) patients. Repeated tests in 116 patients were within the normal range, and 5 patients received treatment. Postoperative bleeding occurred in 4 (0.5%) patients. The relationship between coagulation tests and postoperative bleeding was not significant. PBQ was found to be ≥2 in 14 patients, but none of these patients had postoperative bleeding. No significant relationship was found between postoperative bleeding status and PBQ (p:0.77). The sensitivity, specificity, positive predictive, and negative predictive values of PBQ were 0%, 98%, 0%, and 97.4%, respectively.

Conclusions:

The results of this study demonstrated that neither coagulation tests nor PBQ will be sufficient to predict bleeding after minor surgery, that prolongation in coagulation tests does not always indicate a bleeding tendency, and that bleeding history should also be recorded in detail.
Reducing (Behavioral) Restraint Use Through Simulation at the Bedside
Authors: Miller Olivia , Treseler Jennifer , Pignataro Shelly
Published: May 2024

Hospitals are experiencing an influx of patients in active behavioral crises, leading to restraints as a behavior management strategy. Over 100 staff participated in simulation training designed to manage escalating patient behavior. The training had a direct impact on the reduction of restraint use and increased preparedness and confidence of participants managing escalating patient behavior. Results suggest simulation can be an effective strategy to train medical staff to manage challenging behavior and reduce restraint use.
Escape Rooms in Nursing Education
Authors: Zhao Xue , Brand Gabrielle , Kovach Nicole , Bonnamy James
Published: May 2024

Background:

Escape rooms (ERs) are being increasingly used in nursing education as an active and game-based learning method.

Purpose:

To conduct a systematic review to synthesize evidence on the current use of ERs in nursing education.

Methods:

A mixed methods systematic review was performed to identify and synthesize existing literature. Five databases were searched in July 2023. Descriptive and thematic analysis were used to synthesize quantitative and qualitative data, respectively.

Results:

A total of 333 studies were found after searching 5 databases. After 2 independent reviews, a total of 57 studies were identified across 5 countries. There were 16 qualitative studies, 34 quantitative studies, and 7 mixed methods studies. Four main themes were identified.

Conclusions:

ERs are widely used across different topics and settings in nursing education and are enjoyed by the majority of participants; however, more rigorous research is needed to confirm whether ERs improve learning outcomes.
Prevalence of Genital Herpes and Antiviral Treatment
Authors: Jain Purva , Embry Alan , Arakaki Brent , Estevez Irisdaly , Marcum Zachary A. , Viscidi Emma
Published: May 2024

Background

Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus. Contemporary US population–based epidemiologic data on genital herpes are limited. This study aimed to provide nationally representative estimates of genital herpes prevalence and treatment using a large US health insurance claims database.

Methods

This observational cohort study used administrative claims data from HealthVerity. Crude and age- and sex-standardized prevalence rates of genital herpes and recurrent genital herpes were calculated for the years 2019 to 2021. The distribution of patients with prevalent genital herpes who received episodic or suppressive antiviral therapy was also estimated.

Results

From 2019 to 2021, the standardized prevalence of genital herpes and recurrent genital herpes ranged from 236 to 280 cases per 100,000 person-years and 81 to 98 cases per 100,000 person-years, respectively. The prevalence of genital herpes was highest among those aged 25 to 29 years (prevalence range, 497–582 years), female patients (prevalence range, 348–404 years), and those with a history of HIV infection (prevalence range, 1608–2080 years). The prevalence of recurrent genital herpes was also highest in these groups. From 2019 to 2021, two-thirds of patients (65%–68%) with prevalent genital herpes received antiviral medications; the majority received episodic therapy (80%) rather than suppressive therapy (20%).

Conclusions

The burden of genital herpes and recurrent genital herpes in the United States is substantial, with the highest rates observed in young adults, women, and immunocompromised individuals. About two-thirds receive antiviral treatment each year.
Progress towards achieving national goals for improved quality of life among cis-gender Black women with HIV
Authors: Raiford Jerris L. , Tie Yunfeng , Yuan Xin A. , Byrd Kathy K. , Buchacz Kate A. , Beer Linda
Published: May 2024

Data from the CDC's Medical Monitoring Project indicate that the United States is on track to meet one of five National HIV/AIDS Strategy (NHAS) Quality of Life goals among cisgender Black women, specifically, hunger/food insecurity. Substantial work needs to be done to improve self-rated health and to decrease unmet need for mental health services. Enhanced and coordinated action are necessary to reach all Quality of Life goals in this NHAS priority population.
Risk score prediction for bacteriologically confirmed tuberculosis among adults with HIV on antiretroviral therapy in northwest Ethiopia: prognostic model development
Authors: Derseh Nebiyu Mekonnen , Agimas Muluken Chanie , Tesfie Tigabu Kidie
Published: May 2024

Objective:

This study was aimed at developing a risk score prediction model for bacteriologically confirmed tuberculosis (TB) among adults with HIV receiving antiretroviral therapy in Ethiopia.

Methods:

An institutional-based retrospective follow-up study was conducted among 569 adults with HIV on ART. We used demographic and clinical prognostic factors to develop a risk prediction model. Model performance was evaluated by discrimination and calibration using the area under the receiver operating characteristic (AUROC) curve and calibration plot. Bootstrapping was used for internal validation. A decision curve analysis was used to evaluate the clinical utility.

Results:

Opportunistic infection, functional status, anemia, isoniazid preventive therapy, and WHO clinical stages were used to develop risk prediction. The AUROC curve of the original model was 87.53% [95% confidence interval (CI): 83.88–91.25] and the calibration plot (P-value = 0.51). After internal validation, the AUROC curve of 86.61% (95% CI: 82.92–90.29%) was comparable with the original model, with an optimism coefficient of 0.0096 and good calibration (P-value = 0.10). Our model revealed excellent sensitivity (92.65%) and negative predictive value (NPV) (98.60%) with very good specificity (70.06%) and accuracy (72.76%). After validation, accuracy (74.85%) and specificity (76.27%) were improved, but sensitivity (86.76%) and NPV (97.66%) were relatively reduced. The risk prediction model had a net benefit up to 7.5 threshold probabilities.

Conclusion:

This prognostic model had very good performance. Moreover, it had very good sensitivity and excellent NPV. The model could help clinicians use risk estimation and stratification for early diagnosis and treatment to improve patient outcomes and quality of life.
False-Negative Neuroendocrine Tumor Identified With 68Ga-DOTATOC PET/CT
Authors: Moreau Aurélie , Chaouat Charlotte , Walter Thomas , Dupré Aurélien , Kryza David
Published: May 2024

We report the case of a 25-year-old man who was undergoing follow-up for neurofibromatosis type 1. The man underwent 68Ga-DOTATOC PET/CT for a suspected well-differentiated duodenal neuroendocrine tumor. This examination did not reveal any significant uptake, whereas complementary 18F-FDG PET/CT showed moderate 18F-FDG uptake in the primary tumor as well as the adenopathy. Histology, a well-differentiated duodenal neuroendocrine tumor was confirmed, consistent with the diagnosis of somatostatinoma. Although rare, this well-differentiated neuroendocrine tumor should be kept in mind as a possible source of false-negative somatostatin receptor PET/CT findings.
Ketamine for acute pain after trauma: A pragmatic, randomized clinical trial
Authors: Klugh James M. , Puzio Thaddeus J. , Wandling Michael W. , Guy-Frank Chelsea J. , Green Charles , Sergot Paulina B. , Prater Samuel J. , Balogh Julius , Stephens Christopher T. , Wade Charles E. , Kao Lillian S. , Harvin John A.
Published: May 2024

BACKGROUND

Non-narcotic intravenous medications may be a beneficial adjunct to oral multimodal pain regimens (MMPRs) which reduce but do not eliminate opioid exposure and prescribing after trauma. We hypothesized that the addition of a subdissociative ketamine infusion (KI) to a standardized oral MMPR reduces inpatient opioid exposure.

METHODS

Eligible adult trauma patients admitted to the intermediate or intensive care unit were randomized upon admission to our institutional MMPR per usual care (UC) or UC plus subdissociative KI for 24 hours to 72 hours after arrival. The primary outcome was morphine milligram equivalents per day (MME/d) and secondary outcomes included total MME, discharge with an opioid prescription (OP%), and rates of ketamine side effects. Bayesian posterior probabilities (pp) were calculated using neutral priors.

RESULTS

A total of 300 patients were included in the final analysis with 144 randomized to KI and 156 to UC. Baseline characteristics were similar between groups. The Injury Severity Scores for KI were 19 [14, 29] versus UC 22 [14, 29]. The KI group had a lower rate of long-bone fracture (37% vs. 49%) and laparotomy (16% vs. 24%). Patients receiving KI had an absolute reduction of 7 MME/day, 96 total MME, and 5% in OP%. In addition, KI had a relative risk (RR) reduction of 19% in MME/day (RR, 0.81 [0.69–0.95], pp = 99%), 20% in total MME (RR, 0.80 [0.64–0.99], pp = 98%), and 8% in OP% (RR, 0.92 [0.76–1.11], pp = 81%). The KI group had a higher rate of delirium (11% vs. 6%); however, rates of other side effects such as arrythmias and unplanned intubations were similar between groups.

CONCLUSION

Addition of a subdissociative ketamine infusion to an oral MMPR resulted in a decrease in opioid exposure in severely injured patients. Subdissociative ketamine infusions can be used as a safe adjunct to decrease opioid exposure in monitored settings.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level I.
Prophylactic antibiotic use for penetrating trauma in prolonged casualty care: A review of the literature and current guidelines
Authors: Causbie Jacqueline M. , Wisniewski Piotr , Maves Ryan C. , Mount Cristin A.
Published: May 2024

Prolonged casualty care (PCC), previously known as prolonged field care, is a system to provide patient care for extended periods of time when evacuation or mission requirements surpass available capabilities. Current guidelines recommend a 7- to 10-day course of ertapenem or moxifloxacin, with vancomycin if methicillin-resistant Staphylococcus aureus is suspected, for all penetrating trauma in PCC. Data from civilian and military trauma have demonstrated benefit for antibiotic prophylaxis in multiple types of penetrating trauma, but the recommended regimens and durations differ from those used in PCC, with the PCC guidelines generally recommending broader coverage. We present a review of the available civilian and military literature on antibiotic prophylaxis in penetrating trauma to discuss whether a strategy of broader coverage is necessary in the PCC setting, with the goal of optimizing patient outcomes and antibiotic stewardship, while remaining cognizant of the challenges of moving medical material to and through combat zones. Empiric extended gram-negative coverage is unlikely to be necessary for thoracic, maxillofacial, extremity, and central nervous system trauma in most medical settings. However, providing the narrowest appropriate antimicrobial coverage is challenging in PCC because of limited resources, most notably, delay to surgical debridement. Antibiotic prophylaxis regimen must be determined on a case-by-case basis based on individual patient factors while still considering antibiotic stewardship. Narrower regimens, which focus on matching up the site of infection to the antibiotic chosen, may be appropriate based on available resources and expertise of treating providers. When resources permit in PCC, the narrower cefazolin-based regimens (with the addition of metronidazole for esophageal or abdominal involvement, or gross contamination of central nervous system trauma) likely provide adequate coverage. Levofloxacin is appropriate for ocular trauma. Ideally, cefazolin and metronidazole should be carried by medics in addition to first-line antibiotics (moxifloxacin and ertapenem, Literature Synthesis and Expert Opinion; Level V).
Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care
Authors: Duchesne Juan , McLafferty Bryant J. , Broome Jacob M. , Caputo Sydney , Ritondale Joseph P. , Tatum Danielle , Taghavi Sharven , Jackson-Weaver Olan , Tran Sherman , McGrew Patrick , Harrell Kevin N. , Smith Alison , Nichols Emily , Dransfield Thomas , Marino Megan , Piehl Mark
Published: May 2024

BACKGROUND

Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact.

METHODS

This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. Prehospital blood patients were compared with trauma registry controls from an era before prehospital blood utilization (2016–2019). Included were patients with penetrating injury and SBP ≤ 90 mm Hg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest.

RESULTS

A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs. 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs. 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04–1.19).

CONCLUSION

Compared with patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Quantifying the benefit of whole blood on mortality in trauma patients requiring emergent laparotomy
Authors: Lammers Daniel , Betzold Richard , McClellan John , Eckert Matthew , Bingham Jason , Hu Parker , Hurst Stuart , Baird Emily , Hashmi Zain , Kerby Jeffrey , Jansen Jan O. , Holcomb John B.
Published: May 2024

BACKGROUND

Whole blood (WB) transfusions in trauma represent an increasingly utilized resuscitation strategy in trauma patients. Previous reports suggest a probable mortality benefit with incorporating WB into massive transfusion protocols. However, questions surrounding optimal WB practices persist. We sought to assess the association between the proportion of WB transfused during the initial resuscitative period and its impact on early mortality outcomes for traumatically injured patients.

METHODS

We performed a retrospective analysis of severely injured patients requiring emergent laparotomy and ≥3 units of red blood cell containing products (WB or packed red blood cells) within the first hour from an ACS Level I Trauma Center (2019–2022). Patients were evaluated based on the proportion of WB they received compared with packed red blood cells during their initial resuscitation (high ratio cohort ≥50% WB vs. low ratio cohort <50% WB). Multilevel Bayesian regression analyses were performed to calculate the posterior probabilities and risk ratios (RR) associated with a WB predominant resuscitation for early mortality outcomes.

RESULTS

Two hundred sixty-six patients were analyzed (81% male; mean age, 36 years; 61% penetrating injury; mean Injury Severity Score, 30). The mortality was 11% at 4 hours and 14% at 24 hours. The high ratio cohort demonstrated a 99% (RR, 0.12; 95% credible interval, 0.02–0.53) and 99% (RR, 0.22; 95% credible interval, 0.08–0.65) probability of decreased mortality at 4 hours and 24 hours, respectively, compared the low ratio cohort. There was a 94% and 88% probability of at least a 50% mortality relative risk reduction associated with the WB predominate strategy at 4 hours and 24 hours, respectively.

CONCLUSION

Preferential transfusion of WB during the initial resuscitation demonstrated a 99% probability of being superior to component predominant resuscitations with regards to 4-hour and 24-hour mortality suggesting that WB predominant resuscitations may be superior for improving early mortality. Prospective, randomized trials should be sought.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Geographical and economic influences on neuroimaging modality choice
Authors: Duncan Niall W. , Rae Charlotte L.
Published: May 2024

The current neuroimaging literature is unrepresentative of the world’s population due to bias towards particular types of people living in a subset of geographical locations. This is true of both the people running the research and those participating in it. These biases mean we may be missing insights into how the brain works. As neuroimaging research expands out to more of the world, the reality of global economic disparities becomes salient. With economic conditions having an effect on many background conditions for research, we can ask whether they also inﬂuence the neuroimaging research being done. To investigate this, the number of neuroimaging publications originating from a country was used as a proxy for the type of research being done there in terms of imaging modalities employed. This was then related to local economic conditions, as represented by national gross domestic product and research and development spending. National financial metrics were positively associated with neuroimaging output. The imaging modalities used were also found to be associated with local economic conditions, with magnetic resonance imaging (MRI) research positively and electroencephalography (EEG) negatively associated with national research spending. These results suggest that economic conditions may be relevant when planning how neuroimaging research can be expanded globally.
Transmission dynamics of symbiotic protist communities in the termite gut: association with host adult eclosion and dispersal
Authors: Inagaki Tatsuya , Igai Katsura , Takahashi Kazuki , Hongoh Yuichi
Published: May 2024

The fidelity of vertical transmission is a critical factor in maintaining mutualistic associations with microorganisms. The obligate mutualism between termites and intestinal protist communities has been maintained for over 130 million years, suggesting the faithful transmission of diverse protist species across host generations. Although a severe bottleneck can occur when alates disperse with gut protists, how protist communities are maintained during this process remains largely unknown. In this study, we examined the dynamics of intestinal protist communities during adult eclosion and alate dispersal in the termite
Reticulitermes speratus
. We found that the protist community structure in last-instar nymphs differed significantly from that in workers and persisted intact during adult eclosion, whereas all protists disappeared from the gut during moults between worker stages. The number of protists in nymphs and alates was substantially lower than in workers, whereas the proportion of protist species exhibiting low abundance in workers was higher in nymphs and alates. Using a simulation-based approach, we demonstrate that such changes in the protist community composition of nymphs and alates improve the transmission efficiency of whole protist species communities. This study thus provides novel insights into how termites have maintained mutualistic relationships with diverse gut microbiota for generations.
The quest for dynamic consistency: a comparison of OpenSim tools for residual reduction in simulations of human running
Authors: Fox Aaron S.
Published: May 2024

Using synchronous kinematic and kinetic data in simulations of human running typically leads to dynamic inconsistencies. Minimizing residual forces and moments is subsequently important to ensure plausible model outputs. A variety of approaches suitable for residual reduction are available in OpenSim; however, a detailed comparison is yet to be conducted. This study compared OpenSim tools applicable for residual reduction in simulations of human running. Multiple approaches (i.e. Residual Reduction Algorithm,
MocoTrack
,
AddBiomechanics
) designed to reduce residual forces and moments were examined using an existing dataset of treadmill running at 5.0 ms
−1
. The computational time, residual forces and moments, and joint kinematics and kinetics from each approach were compared. A computational cost to residual reduction trade-off was identified, where lower residuals were achieved using approaches with longer computational times. The
AddBiomechanics
and
MocoTrack
approaches produced variable lower and upper body kinematics, respectively, versus the remaining approaches. Joint kinetics were similar between approaches; however,
MocoTrack
generated noisier upper limb joint torque signals.
MocoTrack
was the best-performing approach for reducing residuals to near-zero levels, at the cost of longer computational times. This study provides OpenSim users with evidence to inform decision-making at the residual reduction step of their workflow.
A Divide-and-Conquer Approach to Large-Scale Evolutionary Analysis of Single-Cell DNA Data
Authors: Liu Yushu , Nakhleh Luay
Published: May 2024

Single-cell sequencing technologies are producing large data sets, often with thousands or even tens of thousands of single-cell genomic data from an individual patient. Evolutionary analyses of these data sets help uncover and order genetic variants in the data as well as elucidate mutation trees and intra-tumor heterogeneity (ITH) in the case of cancer data sets. To enable such large-scale analyses computationally, we propose a divide-and-conquer approach that could be used to scale up computationally intensive inference methods. The approach consists of four steps: 1) partitioning the dataset into subsets, 2) constructing a rooted tree for each subset, 3) computing a representative genotype for each subset by utilizing its inferred tree, and 4) assembling the individual trees using a tree built on the representative genotypes. Besides its flexibility and enabling scalability, this approach also lends itself naturally to ITH analysis, as the clones would be the individual subsets, and the “assembly tree” could be the mutation tree that defines the clones. To demonstrate the effectiveness of our proposed approach, we conducted experiments employing a range of methods at each stage. In particular, as clustering and dimensionality reduction methods are commonly used to tame the complexity of large datasets in this area, we analyzed the performance of a variety of such methods within our approach.
L-Shaped Distributions of the Relative Substitution Rates (c/micro) in SARS-COV-2 with or without Molecular Clocks, Challenging Mainstream Evolutionary Theories
Authors: Wu Chun , Paradis Nicholas J.
Published: May 2024

A definitive test to quantify fitness changes of mutations is required to end a continuing 50-year "neutralist-selectionist" debate in evolutionary biology. Our previous work introduced a substitution-mutation rate ratio c/micro test (c: substitution rate in Translated Region/TR or UnTranslated Region/UTR; micro mutation rate) to quantify the selection pressure and thus the proportions of strictly neutral, nearly neutral, beneficial, and deleterious mutations in a genome. Intriguingly, both a L-shaped probability distribution of c/micro and molecular clock were observed for SARS-COV-2's genome. We found that the proportion of the different mutation types from the distribution is not consistent with the hypotheses of the three existing evolution theories (Kimura's Neutral Theory/KNT, Ohta's Nearly Neutral Theory/ONNT and the Selectionist Theory/ST), and a balance condition explains the molecular clock, thus we proposed a new theory named as Near-Neutral Balanced Selectionist Theory (NNBST). In this study, the c/micro analysis was extended beyond the genome to 26 TRs, 12 UTRs, and 10 TRSs (Transcriptional Regulatory Sequences) of SARS-COV-2. While L-shaped probability distributions of c/micro were observed for all of 49 segments, molecular clocks were observed for only 24 segments, supporting NNBST and Near-Neutral Unbalanced Selectionist Theory (NNUST) to explain the molecular evolution of 24/25 segments with/without molecular clocks. Thus, the Near-Neutral Selectionist Theory (NNST) integrates traditional neutral and selectionist theories to deepen our understanding of how mutation, selection, and genetic drift influence genomic evolution.
Anomalous diffusion analysis reveals cooperative locomotion of adult parasitic nematodes in sex-mixed groups
Authors: Leben Ruth , Rausch Sebastian , Elomaa Laura , Hauser Anja E. , Weinhart Marie , Fischer Sabine C. , Stark Holger , Hartmann Susanne , Niesner Raluca
Published: May 2024

Parasitic worms are widespread throughout the world and causing agents of chronic infections in humans and animals. The majority of these pathogens parasitize the gut of the infected hosts, however very little is known about the locomotion of the worms dwelling the gut. We studied the movement ofHeligmosomoides bakeri (previouslyHeligmosomoides polygyrus), a natural infection of mice and usually used as animal model to study the roundworm infections. We investigated the locomotion ofH. bakeriin simplified environments mimicking key physical features of the intestinal lumen, i.e. various medium viscosities, and a periodical intestinal villi topography. The non-periodical nematode motion in these settings could be described by anomalous diffusion theory. Fascinatingly, an oriented, super-diffusive locomotion of nematodes in sex-mixed groups were detected, in the sense of a cooperative, but not collective (swarm-like) migration stimulated by mating and reproduction, while individual nematodes moved randomly, following a diffusive motion regime. High mucus-like medium viscosity and villi topography, representing physical constraints of nematode locomotion, slowed down but did not prevent this cooperative migration. Additionally, the mean displacement rate of nematodes in sex-mixed groups of 6·10−4mm/s in viscous mucus-like medium are in good agreement with estimates of nematode migration velocities between 10−4to 10−3mm/s in the gut. Thus, our data indicate the intestinal nematodes motion to be non-periodic and random but triggered to be oriented by kin of the different sex.
MDM2 stabilization of Notch intracellular domain upon DNA damage plays a major role in non-small cell lung carcinoma response to platinum chemotherapy
Authors: Bernardo Sara , Thomas Quentin-Dominique , Mancini Maicol , Santos Alba , Rasamizafy Sylvia Fenosoa , Maacha Amina-Milissa , Giry Anais , Bousquet-Mur Emilie , Papon Laura , Goussard Marion , Fremin Christophe , Pasquier Andrea , Rodríguez María , Travert Camille , Pujol Jean-Louis , Linares Laetitia K , Heron-Milhavet Lisa , Djiane Alexandre , Ferrer Irene , Paz-Ares Luis , Quantin Xavier , Montuenga Luis M , Tourriere Hélène , Maraver Antonio
Published: May 2024

Despite major advances in lung cancer clinical management, majority of patients suffering non-small cell lung carcinoma (NSCLC) are treated in first line with platinum in combination with immune checkpoint inhibitors. Although platinum compounds normally display an initial therapeutic effect, relapse constitutes a major challenge in the clinical management of NSCLC patients. Therefore, it is fundamental to understand the relapse underlying mechanisms to find new therapeutic opportunities to improve patients’ survival. Here, we found that different DNA damage inducers increase the protein levels of Notch Intracellular Domain (NICD), i.e., the active form of NOTCH1. Mechanistically, we unveiled that upon platinum treatment, there was a concomitant increase of MDM2 together with NICD, and we also observed an MDM2-mediated ubiquitination and stabilization of NICD. Of note, using patient-derived xenografts displaying intrinsic carboplatin resistance, we demonstrated that the combination of carboplatin with MDM2 and NICD inhibitors increased survival and reduced tumor growth compared with carboplatin in monotherapy. Moreover, in patients with NSCLC who received platinum chemotherapy, MDM2 expression level in the tumor was correlated with poor progression-free survival, further validating MDM2 key role in the response to platinum compounds. Our findings open a therapeutic opportunity for NSCLC patients, the main lung cancer subtype of the leading cause of death by cancer worldwide.
Microstructural pruning in human prefrontal cortex scaffolds its functional reorganization across development
Authors: Yao Jewelia K. , Yazdani Zachariya , Musa Ruggaya , Gomez Jesse
Published: May 2024

Neural representations in occipitotemporal cortex emerge during development in response to visual experience with ecological stimulus categories, such as faces or words. While similar category-selective representations have also been observed in the frontal lobe, how they emerge across development, whether current models of brain development extend to prefrontal cortex, and the extent to which such high-level representations are anatomically consistent across the lifespan is unknown. Through a combination of functional and quantitative MRI scans, we observe previously undescribed cortical folding patterns in human-specific inferior frontal cortex whose consistency reveals that childhood representations for visual object categories rearrange into stable adulthood patterns. This functional restructuring was distinct from occipitotemporal cortex where adult-like response patterns only scale in magnitude across development. The unique form of functional development in prefrontal cortex was accompanied by restructuring of cortical tissue properties: macromolecules are pruned across adolescence in prefrontal cortex while they proliferate in temporal cortex. These results suggest visual representations in distinct cortical lobes undergo distinct developmental trajectories, and that human-specific prefrontal cortex shows an especially protracted maturational process that necessitates late-stage tissue restructuring detectable in the living brain.
Commonly used organoid culture media prevent ferroptosis
Authors: Eaton John K. , Chatterji Priya , Sweat Yan Y. , Victorio Rachelle A. , Wawer Mathias J. , Viswanathan Vasanthi S.
Published: May 2024

Organoids enable the recreation of organ physiologyin vitroand serve as powerful models for biology in basic life science research and drug discovery and development. However, organoid culture requires complex media formulations that include antioxidants, potentially confounding experimental results sensitive to such conditions. Here we report that the growth conditions used commonly to generate organoid models inhibit ferroptosis, an iron-dependent form of lipid peroxidative cell death with relevance to human disease, thus rendering such models incompatible with ferroptosis research. We identify medium components that diminish or eliminate ferroptosis sensitivity and outline strategies for avoiding anti-ferroptotic culture conditions in organoid and other cell culture applications. These findings provide a roadmap for adapting organoid models for the study of ferroptosis and leveraging their strengths for advancing ferroptosis-modulating therapeutics.
Discovery and Quantification of Long-Range RNA Base Pairs in Coronavirus Genomes with SEARCH-MaP and SEISMIC-RNA
Authors: Allan Matthew F. , Aruda Justin , Plung Jesse S. , Grote Scott L. , Martin des Taillades Yves J. , de Lajarte Albéric A. , Bathe Mark , Rouskin Silvi
Published: May 2024

RNA molecules perform a diversity of essential functions for which their linear sequences must fold into higher-order structures. Techniques including crystallography and cryogenic electron microscopy have revealed 3D structures of ribosomal, transfer, and other well-structured RNAs; while chemical probing with sequencing facilitates secondary structure modeling of any RNAs of interest, even within cells. Ongoing efforts continue increasing the accuracy, resolution, and ability to distinguish coexisting alternative structures. However, no method can discover and quantify alternative structures with base pairs spanning arbitrarily long distances – an obstacle for studying viral, messenger, and long noncoding RNAs, which may form long-range base pairs.

Here, we introduce the method of Structure Ensemble Ablation by Reverse Complement Hybridization with Mutational Profiling (SEARCH-MaP) and software for Structure Ensemble Inference by Sequencing, Mutation Identification, and Clustering of RNA (SEISMIC-RNA). We use SEARCH-MaP and SEISMIC-RNA to discover that the frameshift stimulating element of SARS coronavirus 2 base-pairs with another element 1 kilobase downstream in nearly half of RNA molecules, and that this structure competes with a pseudoknot that stimulates ribosomal frameshifting. Moreover, we identify long-range base pairs involving the frameshift stimulating element in other coronaviruses including SARS coronavirus 1 and transmissible gastroenteritis virus, and model the full genomic secondary structure of the latter. These findings suggest that long-range base pairs are common in coronaviruses and may regulate ribosomal frameshifting, which is essential for viral RNA synthesis. We anticipate that SEARCH-MaP will enable solving many RNA structure ensembles that have eluded characterization, thereby enhancing our general understanding of RNA structures and their functions. SEISMIC-RNA, software for analyzing mutational profiling data at any scale, could power future studies on RNA structure and is available on GitHub and the Python Package Index.
Developmental origins and evolution of pallial cell types and structures in birds
Authors: Zaremba Bastienne , Fallahshahroudi Amir , Schneider Céline , Schmidt Julia , Sarropoulos Ioannis , Leushkin Evgeny , Berki Bianka , Van Poucke Enya , Jensen Per , Senovilla-Ganzo Rodrigo , Hervas-Sotomayor Francisca , Trost Nils , Lamanna Francesco , Sepp Mari , García-Moreno Fernando , Kaessmann Henrik
Published: May 2024

The advanced cognitive abilities of birds rival those of mammals and have been attributed to evolutionary innovations in the pallium. However, a comprehensive cellular characterization of this brain region in birds has been lacking. We scrutinized the structures, cell types and evolutionary origins of the avian pallium based on single-cell and spatial transcriptomics atlases for the adult and developing chicken, and comparisons to corresponding data from mammals and non-avian reptiles. We found that the avian pallium shares most inhibitory neuron types with other amniotes. While excitatory neuron repertoires in the (medial) hippocampal formation show high conservation, they substantially diverged in other pallial regions during avian evolution, defining novel structures like the avian-specific (dorsal) hyperpallium, whose neuronal gene expression identities partly converge during late development with those of the (ventral) nidopallium. Our work also unveils the evolutionary relationships of pallial structures across amniotes, like the previously unknown homology between avian (lateral) mesopallial and mammalian deep layer cortical neurons.

One-Sentence Summary

An avian neural cell type atlas illuminates the developmental origins and evolution of the amniote pallium.