bluuebunny/crossref_metadata_2025 huggingface dataset:
STEM-04. BIOBANKING PATIENT-DERIVED MODELS OFFERS A PRECISE SPATIAL AND EPIGENETIC APPROACH TO UNRAVEL THE INITIATION, PROGRESSION, AND THERAPEUTIC RESISTANCE OF PEDIATRIC BRAIN TUMORS
Authors: Deschuyter Marlene , Salmanli Chinar , Wolf Thibaut , Lhermitte Benoit , Reita Damien , Fuchs Quentin , Hubsch Clémence , Foppolo Sophie , Dontenwill Monique , Martin Sophie , Entz-Werlé Natacha
Published: June 2024

BACKGROUND

Aggressive brain cancers represent the most lethal forms of tumors in pediatric population. Their molecular drivers and co-alterations are currently guiding therapeutic strategies. Due to heterogeneous nature of these tumors, they are quickly developing resistance to treatment. Recognizing intrinsic and extrinsic mechanisms underlying therapeutic resistance, international scientific community has recognized an urgent need to create precise models of brain tumors capable of predicting therapeutic responses. So far, patient-derived cell lines (PDCL) remain the most reliable model to estimate and mimic evolving scenarios. The primary challenges lie in derivation methods and in cellular and spatial validation.

METHODS

In the context of the PEDIAMODECAN program, we collected 105 fresh brain tumor samples, including 34 LGG, 24 HGG, 19 ependymomas, 19 medulloblastomas, and 9 other rare entities, to concurrently generate PDCLs and patient-derived xenografts (PDX).

RESULTS

Regarding the derivation process itself, we successfully maintained 80% of samples in 2D and 54% in PDX models. As anticipated, the LGG group showed the higher percentage of PDX failure (90%). Nevertheless, for high-grade subtypes, PDX generation rate increased to 85,7%. No correlation was found between derivation success and a shorter interval between surgical removal and dissociation processes. Histological analysis of PDXs models confirmed the similar microscopic features to those of primary tumors. Next-Generation Sequencing (NGS), methylome assays and spatial transcriptomic analyses of derived models matched those of the original patient tumors. Epigenetic approaches were proved to be the most effective methods for validating models, in addition to spatial transcriptomic analyses that highlighted similar inter-tumor heterogeneity between PDX models and primary tumor counterparts.

CONCLUSIONS

Establishing a systematic PDCL/PDX biobank for all pediatric brain tumors represents one of the most effective approaches to develop models capable of accurately reproducing tumoral heterogeneity, histological and molecular diversity, and facilitating the design predictive screenings for targeted therapies combined with irradiation.
STEM-08. ANGIOGENESIS IN PEDIATRIC CHOROID PLEXUS PAPILLOMAS
Authors: Sulaiman Nurfarhanah Bte Syed , Merchant Khurshid Z , Seow Wan Tew , Ng Lee Ping , Low Sharon Y Y
Published: June 2024

BACKGROUND

Choroid plexus papillomas (CPP) are rare brain tumors that tend to occur in very young children. Although most of them are curative with surgical resection, a subset of them has propensity for tumor recurrence, progression, and metastasis. Moreover, surgery can be technically difficult due to their deep locations and high vascularity. In-depth mechanisms of their biology remain poorly understood. Separately, the process of angiogenesis has been implicated in several cancers. To date, there has been no previous study focused on CPP and angiogenesis. This study aims to explore and ascertain the existence of angiogenesis in CPP.

METHODS

This is a study approved by the hospital ethics review board. Cerebrospinal fluid (CSF) and CPP tumor samples are collected at the time of surgery. A multiplex immunoassay panel is used to measure cytokine concentrations in the CSF samples. Identified cytokines of interest are input into online platforms to assess for protein-protein interaction pathways. Concurrently, patient-derived primary cell cultures and their supernatants are derived from CPP samples. A targeted proteome blot array and HUVEC tubule formation assays are used to validate clinical and in silico findings.

RESULT

CSF profiling showed higher expression of MCP-1, MMP-1, IL-2, TNF-ɑ, TRAIL and CD40-L in CPP patient samples versus non-tumor controls. Next, in silico assessment via STRING and BioGRID platforms report that these cytokines are associated with endothelial cell regulation. This is clinically relevant as we are aware that the endothelium has important functions in the regulation of angiogenesis. Using an angiogenesis-focused approach, CPP-derived cell lines and supernatants showed congruently higher expression of MCP-1, MMP-1 and TNF-ɑ. Next, tubule formation was observed in HUVEC cultures where conditioned CPP cell culture media was added.

CONCLUSIONS

Based on our preliminary findings, this proof-of-concept study demonstrates potential to explore the role of angiogenesis in CPP for better disease understanding.
Plasma Microbial Cell-free DNA Next-generation Sequencing Can Be a Useful Diagnostic Tool in Patients With Osteoarticular Infections
Authors: Petri Francesco , Mahmoud Omar K , Ranganath Nischal , El Zein Said , Abu Saleh Omar , Berbari Elie F , Fida Madiha
Published: June 2024

Background

Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges.

Methods

We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information.

Results

In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P < .001) or OAIs with concomitant presence of endocarditis or endovascular infection (P = .005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result.

Conclusions

In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients.
Innovations in Survey Research
Authors: Cooksey Elizabeth , Herrera Lucia , Hoffman Jenifer , Rusnak Laura
Published: June 2024

A survey panel is a group of people who have been recruited by various means, provided some basic demographic profile data, and agreed to share their opinions when asked to take part in specific surveys. This chapter highlights various panels used by researchers over the past couple of decades to draw samples for their own study surveys. Probability and non-probability samples are distinguished and pros and cons of each are outlined. The American Population Panel (APP) is then described and used to illustrate mechanics underlying panel initiation, growth and maintenance, along with problems encountered in the process (for example, fraud among potential respondents). The ways in which the APP can serve specific research needs such as questionnaire pilot testing, finding specific population subgroups, and following the same respondents over time are discussed.
Tacrolimus personalized therapy based on CYP3A5 genotype in Chinese patients with idiopathic inflammatory myopathies
Authors: Tian Xueke , Liu Lijun , Liu Shengyun , Yang Jing
Published: June 2024

Objective

Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases; in particular, anti-melanoma differentiation-associated gene 5 antibody positive DM (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin)–outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients.

Methods

A total of 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed.

Results

TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all-phase IIM patients (P = 0.001, 0.013, 0.002 and <0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all-phase MDA5+ DM patients (P = 0.007, 0.001, 0.036 and <0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/day to attain the target Cmin, while nonexpressers required 0.046 mg/kg/day (P = 0.019).

Conclusion

TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to a lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM.
The Effort of Repairing a Misperceived Word Can Impair Perception of Following Words, Especially for Listeners With Cochlear Implants
Authors: Winn Matthew B.
Published: June 2024

Objectives:

In clinical and laboratory settings, speech recognition is typically assessed in a way that cannot distinguish accurate auditory perception from misperception that was mentally repaired or inferred from context. Previous work showed that the process of repairing misperceptions elicits greater listening effort, and that this elevated effort lingers well after the sentence is heard. That result suggests that cognitive repair strategies might appear successful when testing a single utterance but fail for everyday continuous conversational speech. The present study tested the hypothesis that the effort of repairing misperceptions has the consequence of carrying over to interfere with perception of later words after the sentence.

Design:

Stimuli were open-set coherent sentences that were presented intact or with a word early in the sentence replaced with noise, forcing the listener to use later context to mentally repair the missing word. Sentences were immediately followed by digit triplets, which served to probe carryover effort from the sentence. Control conditions allowed for the comparison to intact sentences that did not demand mental repair, as well as to listening conditions that removed the need to attend to the post-sentence stimuli, or removed the post-sentence digits altogether. Intelligibility scores for the sentences and digits were accompanied by time-series measurements of pupil dilation to assess cognitive load during the task, as well as subjective rating of effort. Participants included adults with cochlear implants (CIs), as well as an age-matched group and a younger group of listeners with typical hearing for comparison.

Results:

For the CI group, needing to repair a missing word during a sentence resulted in more errors on the digits after the sentence, especially when the repair process did not result in a coherent sensible perception. Sentences that needed repair also contained more errors on the words that were unmasked. All groups showed substantial increase of pupil dilation when sentences required repair, even when the repair was successful. Younger typical hearing listeners showed clear differences in moment-to-moment allocation of effort in the different conditions, while the other groups did not.

Conclusions:

For CI listeners, the effort of needing to repair misperceptions in a sentence can last long enough to interfere with words that follow the sentence. This pattern could pose a serious problem for regular communication but would go overlooked in typical testing with single utterances, where a listener has a chance to repair misperceptions before responding. Carryover effort was not predictable by basic intelligibility scores, but can be revealed in behavioral data when sentences are followed immediately by extra probe words such as digits.
Impact of Spinal Surgery on Intrathecal Nusinersen Injections in Pediatric Spinal Muscular Atrophy
Authors: Aksoy Taha , Ramazanov Rafik , Öz Yildiz Sibel , Demirkiran Gökhan , Haliloğlu Göknur , Yazici Muharrem
Published: June 2024

Background:

Complex spinal deformities necessitate surgical interventions that may intervene with intrathecal injections in patients with spinal muscular atrophy (SMA). This study aimed to determine the effect of spinal deformity correction surgery on nusinersen administration.

Methods:

Pediatric patients with SMA, operated by a single surgeon, either via magnetically controlled growing rod (MCGR) or definitive fusion (DF) with skip instrumentation, were evaluated retrospectively in terms of safety and feasibility of intrathecal injections. Patients’ and their parents’ perspectives were evaluated through a questionnaire regarding any shift in the setting of injections.

Results:

Fourteen patients with 15 spinal surgeries (10 MCGR and 5 DF) were included. Eleven patients received intrathecal treatment both before and after the surgery. Preoperative (n=3) and postoperative (n=9) fluoroscopic guidance was required leading to a shift in the application settings in 6 patients. Of 106 preoperative injections, 15% required fluoroscopy and 2% required anesthesia. Postoperatively, of 88 injections, 73% required fluoroscopy and 26% required anesthesia. No patients discontinued intrathecal injections due to technical difficulties associated with the spinal surgery.

Conclusions:

This study demonstrates that spinal surgery does not prevent safe and successful intrathecal nusinersen injections. In the DF group, the skip instrumentation technique provided access to interlaminal space for intrathecal injections. In either surgical group, no further auxillary approach was required. Modifications in the injection technique require an institutional approach, and concerns of patients and their families should be addressed accordingly.

Level of Evidence:

IV
Menopause and brain fog: how to counsel and treat midlife women
Authors: Maki Pauline M. , Jaff Nicole G.
Published: June 2024

Brain fog, referring to menopause-related subjective cognitive difficulties, is common in midlife women. Longitudinal studies find small but reliable declines in objective memory performance as women transition into perimenopause, and these are not explained by advancing age alone. When memory declines occur, performance levels remain within normal limits for all but a very small number of women. Women’s experience of brain fog extends beyond memory complaints, reflecting the negative effect on a broad range of cognitive abilities. Clinicians can counsel women about how menopause symptoms, estrogen, hormone therapy, and modifiable risk factors (eg, hypertension, sedentary lifestyle) can influence cognitive health.
The Impact of Donor History of Sleep Apnea on Corneal Tissue Evaluation Parameters
Authors: Ramini Abhishek , Zhang Nancy , Lee Megan , Vadakkepattath Indu , Sawant Onkar B. , Bouchard Charles S.
Published: June 2024

Purpose:

The goal of this study was to explore whether the donor history of sleep apnea affects corneal tissue evaluation parameters.

Methods:

This was a retrospective study assessing the impact of donor history of sleep apnea in a dataset obtained from the Eversight Eye Bank. Comparative analysis and multivariate regression were used to assess differences in key parameters including endothelial cell density (ECD) and central corneal thickness.

Results:

Data analyzed consisted of 50,170 tissues from 25,399 donors with no history of sleep apnea and 5473 tissues from 2774 donors with a history of sleep apnea. Tissue from donors with a history of sleep apnea showed lower ECD than those from donors with no history of sleep apnea (−51 cells/mm2, P < 0.001). Multivariate linear regression demonstrated that history of sleep apnea was a predictor of lower ECD by 13.72 cells/mm2 (P = 0.0264). Secondary analysis demonstrated that underweight and obese body mass indexes were significant predictors of increased ECD in donors with no history of sleep apnea (P < 0.0001, P = 0.025, respectively). Body mass index category was not a significant predictor of ECD in donors with a history of sleep apnea. In a smaller subset of 10,756 tissues, sleep apnea was not a significant predictor of central corneal thickness.

Conclusions:

This is the first study to demonstrate that a donor's history of sleep apnea is associated with a lower ECD in a large eye bank dataset. Future studies are needed to investigate whether history of sleep apnea affects posttransplantation outcomes.
The effects of a Teddybear Hospital project on prescool childrens’ knowledge and medical students’ professionalism: a prospective cohort study
Authors: Mildenberger Julia E. , Cámara Rafael , Muensterer Oliver J.
Published: June 2024

Background:

The Teddybear Hospital (TH) Project is an effort to increase children’s knowledge and decrease their anxiety. It is also intended to improve medical students’ pediatric communication skills. This study evaluated the educational effects on participating preschool children and medical students.

Methods:

Preschool children were offered to bring their stuffed toys to the TH at our tertiary academic medical center. Medical students who had completed the pediatric surgery rotation staffed the TH, performed examinations, and interacted with the children. The children’s knowledge of anatomy, medical equipment, and healthy lifestyle, along with their level of anxiety towards hospitalization, was assessed using preinterventional and postinterventional validated survey tools. Preschool peers who did not participate in the TH served as controls. Participating medical students were tested on professionalism and pediatric surgical knowledge during, and 3 weeks after the intervention, and compared to their nonparticipating peers.

Results:

A total of 131 children (63 intervention, 68 control) and 48 medical students (16 intervention, 32 control) participated in the study. Children’s state anxiety decreased by 0.98 points (95% CI: −0.3 to −1.8, P<0.001), while knowledge increased significantly on ‘healthy lifestyle’ by 1.4 points (95% CI: 1.01–1.79, P<0.05), on ‘medical equipment’ by 4.5 points (95% CI: 3.8–5.2, P<0.0001), and on ‘anatomy’ by 5.05 points (95% CI: 4.73–5.73, P<0.01). No changes were detected in any of the outcome measures in the control group. Medical students’ objective professionalism increased by 4.2 points (95% CI: 1.58–6.80, P<0.01) compared to nonparticipant medical students. The tests did not show an increase in the medical students’ pediatric surgical knowledge.

Conclusions:

Preschool participation in a TH increased knowledge and decreased anxiety regarding hospitalization and medical personnel. It also helped medical students to playfully acquire medical professionalism.
Racial, ethnic, and sex disparities in the utilization and outcomes of tricuspid valve surgery
Authors: Ismayl Mahmoud , Ahmed Hasaan , Goldsweig Andrew M. , Alkhouli Mohamad , Guerrero Mayra
Published: June 2024

Background:

Data on racial/ethnic and sex disparities in the utilization and outcomes of tricuspid valve surgery (TVS) in the United States are scarce. The authors aimed to evaluate the impact of race/ethnicity and sex on the utilization and outcomes of TVS.

Methods:

The authors analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for TVS. Racial/ethnic and sex disparities in TVS outcomes were determined using logistic regression models.

Results:

Between 2016 and 2020, 19 395 hospitalizations for TVS were identified. The utilization rate (number of surgeries/100,000 hospitalizations) was lower in Black and Hispanic patients compared with White patients for surgical tricuspid valve repair (STVr) (331 versus 493 versus 634, P<0.01) and surgical tricuspid valve replacement (STVR) (312 versus 601 versus 728, P<0.01). Similarly, the utilization rate was lower for women compared with men for STVr (1021 versus 1364, P<0.01) and STVR (930 versus 1,316, P<0.01). Compared to White men undergoing TVS, all women had lower odds of acute kidney injury [adjusted odds ratio (aOR) 0.65, 95% CI 0.55–0.78] and higher odds of blood transfusion (aOR 1.30, 95% CI 1.07–1.59), and Black men had higher odds of blood transfusion (aOR 1.59, 95% CI 1.08–2.35). In-hospital mortality and other surgical complications were similar between all groups (all P>0.05).

Conclusions:

Significant racial/ethnic and sex disparities exist in the utilization of TVS in the United States. Further studies are needed to understand the reasons for these disparities and to identify effective strategies for their mitigation.
Microsurgical lesionectomy for drug-resistant insular cortex epilepsy in focal cortical dysplasia type IIB: a pediatric case report
Authors: Venkatesan Sanjeevi , Scalia Gianluca , Kumar V R Roopesh , Rajendran Adhithyan , Jeyaraj Malcom , Umana Giuseppe Emmanuele , Chaurasia Bipin
Published: June 2024

Introduction and importance:

Focal cortical dysplasia (FCD) is a significant cause of drug-resistant epilepsy, often necessitating surgical intervention. Type IIb FCD poses challenges due to its strong association with drug-resistant seizures. Effective management involves advanced imaging, intraoperative neurophysiological monitoring, and precise surgical techniques. This case study illustrates these strategies in an 11-year-old female with drug-resistant epilepsy attributed to Type IIb FCD.

Case presentation:

The patient, an 11-year-old female, had drug-resistant seizures despite various anticonvulsant treatments. Preoperative 3 Tesla (3T) MRI revealed an ill-defined lesion in the right frontal operculum. The surgical team used neuro-navigation for intraoperative guidance and electrocorticography for lesionectomy. Pathology confirmed Type IIb FCD with rare concentric calcifications.

Clinical discussion:

Drug-resistant seizures in FCD often require surgery when medications fail. This case highlights the importance of comprehensive preoperative evaluations and advanced imaging, such as 3T MRI, to accurately identify lesions. Intraoperative neurophysiological monitoring, including electrocorticography, ensures precise resection of the epileptogenic zone. The unusual finding of concentric calcifications in Type IIb FCD is noteworthy, suggesting the need for further research to understand their impact on the disease.

Conclusion:

Microsurgical lesionectomy is crucial for managing drug-resistant seizures in Type IIb FCD. Combining advanced imaging with intraoperative monitoring improves surgical precision and outcomes. The rare pathological finding of calcifications highlights the diversity of FCD manifestations, warranting further study. These techniques can significantly enhance seizure control and quality of life in patients with drug-resistant epilepsy.
How does combining physical therapy with transcranial direct stimulation improve upper-limb motor functions in patients with stroke? A theory perspective
Authors: Albishi Alaa. M.
Published: June 2024

More than half of stroke survivors suffer from upper-limb dysfunction that persists years after stroke, negatively impacting patients’ independence and, therefore, affecting their quality of life. Intense motor rehabilitation is required after a stroke to facilitate motor recovery. More importantly, finding new ways to maximize patients’ motor recovery is a core goal of stroke rehabilitation. Thus, researchers have explored the potential benefits of combining the effects of non-invasive brain stimulation with physical therapy rehabilitation. Specifically, combining transcranial direct stimulation (tDCS) with neurorehabilitation interventions can boost the brain’s responses to interventions and maximize the effects of rehabilitation to improve upper-limb recovery post-stroke. However, it is still unclear which modes of tDCS are optimal for upper-limb motor recovery in patients with stroke when combined with physical therapy interventions. Here, the authors review the existing literature suggesting combining physical therapy rehabilitation with tDCS can maximize patients’ motor recovery using the Interhemispheric Competition Model in Stroke. The authors focus on two main rehabilitation paradigms, which are constraint-induced movement therapy (CIMT) and Mirror therapy with and without tDCS. The authors also discuss potential studies to elucidate further the benefit of using tDCS adjunct with these upper-limb rehabilitation paradigms and its effectiveness in patients with stroke, with the ultimate goal of maximizing patients’ motor recovery.
TRENDS AND OUTCOMES IN SEPSIS HOSPITALIZATIONS WITH AND WITHOUT ACUTE KIDNEY INJURY: A NATIONWIDE INPATIENT ANALYSIS
Authors: Li Haibo , Yu Ran , Zhou Qi , Song Jiannan , Zhou Qi , Ma Wanli , Wang Jian , Hu Zhanfei , Yang Qinfeng , Chen Keyuan
Published: June 2024

Background: Despite rapid advances in treatment, sepsis currently remains a major public health challenge worldwide. Over the past several years, there has been an increase in the clinical incidence of sepsis, as well as an increase in hospitalization rates, which bear the majority of the economic burden associated with sepsis. Sepsis is a public health burden due to the high fatality rates and accompanying morbidity. However, the sepsis-related mortality rates have fallen steadily over the years. One of the most common organs to fail in patients with sepsis is the kidney, and acute kidney injury (AKI) is associated with high mortality rates. This study's primary goal was to assess the impact of AKI on the evolution and outcome of hospitalization of patients with sepsis. Methods: Adults (≥18 years) hospitalized for sepsis in the United States between 2010 and 2019 were retrospectively analyzed using the nationally representative Nationwide Inpatient Sample database. Sepsis and AKI were defined using the codes of the International Classification of Diseases, Ninth Revision, Clinical Modification and the International Classification of Diseases, Tenth Revision, Clinical Modification. Results: Of the 4,258,360 outcomes, 3,946,048 met the inclusion criteria. The prevalence of AKI among sepsis inpatients increased from 39.10% in 2010 to 41% in 2019, but the impact of AKI on mortality declined over time, with in-hospital mortality from AKI among sepsis inpatients decreasing from 26.30% in 2010 to 16.30% in 2019. Hospitalizations linked to AKI were substantially more likely to involve infection sites such as the urinary tract, gastrointestinal tract, and endocarditis. Numerous pathogenic floras, including Escherichia coli, Staphylococcus aureus, Streptococcal, Enterococcus, and Pseudomonas, had greater rates among sepsis-related contacts with AKI. Furthermore, compared to hospitalization without comorbid AKI, the median total hospital charges and length of stay days for sepsis hospitalization with comorbid AKI were greater. Conclusion: With time, patients with sepsis have a higher frequency of AKI and a corresponding decline in mortality.
EVALUATION OF VASOPRESSOR INFLECTION POINT FOR SHORT-TERM PROGNOSIS OF PATIENTS WITH SEPTIC SHOCK
Authors: Yang Mei , Chen Shao-Gui
Published: June 2024

Objective: The goal of this study is to investigate the clinical value of vasopressor inflection points in the evaluation of short-term prognosis among individuals afflicted with septic shock. Methods: A retrospective analysis was conducted on a cohort comprising 56 patients diagnosed with septic shock and receiving treatment at the department of critical care medicine of the hospital between January 2021 and March 2023. These patients were divided into two groups based on the prognostic outcome: a survival group consisting of 34 patients and a death group consisting of 22 patients. The determination of vasopressor inflection time and procalcitonin (PCT) inflection time of each patient was undertaken with the initiation of vasopressor therapy serving as the reference point. The vasopressor inflection point was defined as the time when the dosage of vasopressors commenced decreasing, while the PCT inflection point denoted the time when PCT levels began to decline. The incidence of patients reaching the vasopressor and PCT inflection points on the 2nd, 3rd, and 4th days following the initiation of vasopressor therapy was tabulated for both groups. The comparison of inflection points between the two groups at each time point was conducted using Fisher’s exact test. Furthermore, logistic regression analysis was employed for univariate prognostic assessment. The diagnostic performance of vasopressor and PCT inflection point was assessed using the four-table method. The discrepancy and consistency between the two methods were evaluated through paired chi-squared test and Kappa consistency test. Results: The vasopressor inflection point demonstrates promising utility in the assessment of short-term prognosis among patients with septic shock, exhibiting sensitivities of 76.4%, 88.2%, and 100%, specificities of 90.9%, 90.9%, and 86.4%, positive predictive values of 92.9%, 93.8%, and 91.9%, and negative predictive values of 71.4% on the 2nd, 3rd, and 4th day, respectively. Correspondingly, the Youden indices were calculated as 0.673, 0.791, and 0.864 on these respective days. Notably, all metrics at comparable intervals surpassed those of the PCT inflection point. Conclusion: The vasopressor inflection point presents as a robust prognostic tool for the short-term outcomes in patients with septic shock and exhibits superiority over PCT in prognostic assessment.
Modelling the dynamic vaccination game with evolutionary feedback: exploring pairwise interactions and vaccine strategies
Authors: Nabi Khondoker Nazmoon , Kabir K. M. Ariful
Published: June 2024

A novel approach rooted in co-evolutionary game theory has been introduced to investigate how the interaction between human decision-making and the dynamics of the epidemic environment can shape vaccine acceptance during disease outbreaks. This innovative framework combines two key game concepts: the cooperation–defection game and the cost–benefit vaccination game. By doing so, it enables us to delve into the various factors that influence the success of a vaccination campaign amid an outbreak. Within this framework, individuals engage in a thorough evaluation of the risks, benefits and incentives associated with either cooperating by getting vaccinated or defecting by refusing the vaccine. Additionally, it involves a careful analysis of the costs and benefits linked to vaccine acceptance. The outcomes of this study stress the importance of two main factors: the effectiveness of the vaccine and the prevalence of a cooperative culture within society. This insight into the strategic interactions between individuals and their decisions about vaccination holds significant implications for public health policymakers. It equips to boost vaccination coverage and address vaccine hesitancy within society ultimately contributing to better public health outcomes during epidemic outbreaks.
Temperature and water availability drive insect seasonality across a temperate and a tropical region
Authors: van Dijk Laura J. A. , Fisher Brian L. , Miraldo Andreia , Goodsell Robert M. , Iwaszkiewicz-Eggebrecht Elzbieta , Raharinjanahary Dimby , Rajoelison Eric Tsiriniaina , Łukasik Piotr , Andersson Anders F. , Ronquist Fredrik , Roslin Tomas , Tack Ayco J. M.
Published: June 2024

The more insects there are, the more food there is for insectivores and the higher the likelihood for insect-associated ecosystem services. Yet, we lack insights into the drivers of insect biomass over space and seasons, for both tropical and temperate zones. We used 245 Malaise traps, managed by 191 volunteers and park guards, to characterize year-round flying insect biomass in a temperate (Sweden) and a tropical (Madagascar) country. Surprisingly, we found that local insect biomass was similar across zones. In Sweden, local insect biomass increased with accumulated heat and varied across habitats, while biomass in Madagascar was unrelated to the environmental predictors measured. Drivers behind seasonality partly converged: In both countries, the seasonality of insect biomass differed between warmer and colder sites, and wetter and drier sites. In Sweden, short-term deviations from expected season-specific biomass were explained by week-to-week fluctuations in accumulated heat, rainfall and soil moisture, whereas in Madagascar, weeks with higher soil moisture had higher insect biomass. Overall, our study identifies key drivers of the seasonal distribution of flying insect biomass in a temperate and a tropical climate. This knowledge is key to understanding the spatial and seasonal availability of insects—as well as predicting future scenarios of insect biomass change.
Nascent transcription reveals regulatory changes in extremophile fishes inhabiting hydrogen sulfide-rich environments
Authors: Perry Blair W. , McGowan Kerry L. , Arias-Rodriguez Lenin , Duttke Sascha H. , Tobler Michael , Kelley Joanna L.
Published: June 2024

Regulating transcription allows organisms to respond to their environment, both within a single generation (plasticity) and across generations (adaptation). We examined transcriptional differences in gill tissues of fishes in the
Poecilia mexicana
species complex (family Poeciliidae), which have colonized toxic springs rich in hydrogen sulfide (H
2
S) in southern Mexico. There are gene expression differences between sulfidic and non-sulfidic populations, yet regulatory mechanisms mediating this gene expression variation remain poorly studied. We combined capped-small RNA sequencing (csRNA-seq), which captures actively transcribed (i.e. nascent) transcripts, and messenger RNA sequencing (mRNA-seq) to examine how variation in transcription, enhancer activity, and associated transcription factor binding sites may facilitate adaptation to extreme environments. csRNA-seq revealed thousands of differentially initiated transcripts between sulfidic and non-sulfidic populations, many of which are involved in H
2
S detoxification and response. Analyses of transcription factor binding sites in promoter and putative enhancer csRNA-seq peaks identified a suite of transcription factors likely involved in regulating H
2
S-specific shifts in gene expression, including several key transcription factors known to respond to hypoxia. Our findings uncover a complex interplay of regulatory processes that reflect the divergence of extremophile populations of
P. mexicana
from their non-sulfidic ancestors and suggest shared responses among evolutionarily independent lineages.
Weak response to selection on stigma–anther distance in a primarily selfing population of yellow monkeyflower
Authors: Tisinai Shelby L. , Busch Jeremiah W.
Published: June 2024

Stebbins hypothesized that selfing lineages are evolutionary dead ends because they lack adaptive potential. While selfing populations often possess limited nucleotide variability compared with closely related outcrossers, reductions in the genetic variability of quantitative characters remain unclear, especially for key traits determining selfing rates. Yellow monkeyflower (
Mimulus guttatus
) populations generally outcross and maintain extensive quantitative genetic variation in floral traits. Here, we study the Joy Road population (Bodega Bay, CA, USA) of
M. guttatus
, where individuals exhibit stigma–anther distances (SAD) typical of primarily selfing monkeyflowers. We show that this population is closely related to nearby conspecifics on the Pacific Coast with a modest 33% reduction in genome-wide variation compared with a more highly outcrossing population. A five-generation artificial selection experiment challenged the hypothesis that the Joy Road population harbours comparatively low evolutionary potential in stigma-anther distance, a critical determinant of selfing rate in
Mimulus
. Artificial selection generated a weak phenotypic response, with low realized heritabilities (0.020–0.028) falling 84% below those measured for floral characters in more highly outcrossing
M. guttatus
. These results demonstrate substantial declines in evolutionary potential with a transition toward selfing. Whether these findings explain infrequent reversals to outcrossing or general limits on adaptation in selfers requires further investigation.
Functional adaptation of the infant craniofacial system to mechanical loadings arising from masticatory forces
Authors: Liang Ce , Landi Federica , Çetin Izel Ezgi , Profico Antonio , Buzi Costantino , Dutel Hugo , Khonsari Roman Hossein , O'Higgins Paul , Moazen Mehran
Published: June 2024

The morphology and biomechanics of infant crania undergo significant changes between the pre- and post-weaning phases due to increasing loading of the masticatory system. The aims of this study were to characterize the changes in muscle forces, bite forces and the pattern of mechanical strain and stress arising from the aforementioned forces across crania in the first 48 months of life using imaging and finite element methods. A total of 51 head computed tomography scans of normal individuals were collected and analysed from a larger database of 217 individuals. The estimated mean muscle forces of temporalis, masseter and medial pterygoid increase from 30.9 to 87.0 N, 25.6 to 69.6 N and 23.1 to 58.9 N, respectively (0–48 months). Maximum bite force increases from 90.5 to 184.2 N (3–48 months). There is a change in the pattern of strain and stress from the calvaria to the face during postnatal development. Overall, this study highlights the changes in the mechanics of the craniofacial system during normal development. It further raises questions as to how and what level of changes in the mechanical forces during the development can alter the morphology of the craniofacial system.
Patterns and inferred causes of liana mortality in a tropical forest
Authors: Gora Evan M. , DeFilippis David M. , Schnitzer Stefan A.
Published: June 2024

Lianas are major contributors to tropical forest dynamics, yet we know little about their mortality. Using overlapping censuses of the lianas and trees across a 50 ha stand of moist tropical forest, we contrasted community-wide patterns of liana mortality with relatively well-studied patterns of tree mortality to quantify patterns of liana death and identify contributing factors. Liana mortality rates were 172% higher than tree mortality rates, but species-level mortality rates of lianas were similar to trees with ‘fast’ life-history strategies and both growth forms exhibited similar spatial and size-dependent patterns. The mortality rates of liana saplings (<2.1 cm in diameter), which represent about 50% of liana individuals, decreased with increasing disturbance severity and remained consistently low during post-disturbance stand thinning. In contrast, larger liana individuals and trees of all sizes had elevated mortality rates in response to disturbance and their mortality rates decreased over time since disturbance. Within undisturbed forest patches, liana mortality rates increased with increasing soil fertility in a manner similar to trees. The distinct responses of liana saplings to disturbance appeared to distinguish liana mortality from that of trees, whereas similarities in their patterns of death suggest that there are common drivers of woody plant mortality.
Genome sequence and RNA-seq analysis reveal genetic basis of flower coloration in the giant water lilyVictoria cruziana
Authors: Nowak Melina Sophie , Harder Benjamin , Meckoni Samuel Nestor , Friedhoff Ronja , Wolff Katharina , Pucker Boas
Published: June 2024

Victoria cruziana is well known for its huge floating leaves covered with sharp spines and its night blooming. Reports indicate that white flowers open during the first night and turn light pinkish during the following day and the second night. Here, we set out to unravel the molecular basis and ecological function of the flower color change in V. cruziana. A high quality genome sequence with a N50 of 14.3 Mbp and a total assembly size of 3.54 Gbp was generated as the genetic basis for this study. Comparative transcriptomics revealed the genes required for anthocyanin biosynthesis genes and their transcriptional regulators as differentially expressed between the white and the light pinkish stage of a flower. Structural genes with expression differences between white and light pinkish flower stages include VcrF3'H, VcrF3'5'H, VcrDFR, VcrANS, and VcrarGST. The expression pattern of the corresponding transcription factors VcrMYB123, VcrMYB-SG6_a, VcrMYB-SG6_b, VcrTT8, and VcrTTG1 also showed differences that aligned with the flower color.
Densely sampled stimulus-response map of human cortex with single pulse TMS-EEG and its relation to whole brain neuroimaging measures
Authors: Sun Yinming , Lucas Molly V , Cline Christopher C , Menezes Matthew C , Kim Sanggyun , Badami Faizan S , Narayan Manjari , Wu Wei , Daskalakis Zafiris J , Etkin Amit , Saggar Manish
Published: June 2024

Large-scale networks underpin brain functions. How such networks respond to focal stimulation can help decipher complex brain processes and optimize brain stimulation treatments. To map such stimulation-response patterns across the brain non-invasively, we recorded concurrent EEG responses from single-pulse transcranial magnetic stimulation (i.e., TMS-EEG) from over 100 cortical regions with two orthogonal coil orientations from one densely-sampled individual. We also acquired Human Connectome Project (HCP)-styled diffusion imaging scans (six), resting-state functional Magnetic Resonance Imaging (fMRI) scans (120 mins), resting-state EEG scans (108 mins), and structural MR scans (T1- and T2-weighted). Using the TMS-EEG data, we applied network science-based community detection to reveal insights about the brain's causal-functional organization from both a stimulation and recording perspective. We also computed structural and functional maps and the electric field of each TMS stimulation condition. Altogether, we hope the release of this densely sampled (n=1) dataset will be a uniquely valuable resource for both basic and clinical neuroscience research.
Crystal structure of tricarbonyl[η4-6-exo-(triphenylphosphino)cyclohepta-2,4-dien-1-one]iron(0) tetrafluoroborate
Authors: Wong Kelsey C. , Reinheimer Eric W. , Nataro Chip , Griffith Daniel R.
Published: June 2024

The molecular structure of tricarbonyl[η4-6-exo-(triphenylphosphino)cyclohepta-2,4-dien-1-one]iron(0) tetrafluoroborate dichloromethane hemisolvate, [Fe(C28H22O4)(CO)3]BF4·0.5CH2Cl2, as determined by single-crystal X-ray diffraction is reported. The two independent tricarbonyl[η4-6-exo-(triphenylphosphino)cyclohepta-2,4-dien-1-one] iron(0) cations and their corresponding anions form dimers, which constitute the asymmetric unit of the structure parallel to the (100) plane. Solid-state stability within that asymmetric unit as well as between neighboring dimeric units is afforded by C—H...O and C—H...F hydrogen bonds and C—H...π and Y—X...π (Y = B, C; X = F, O) interactions, which yield diperiodic sheets and a three-dimensional extended network.
The antecedents, outcomes and mediating role of inclusion at work
Authors: Duong Ngoc S. , Fry Trevor N. , DeChurch Alexander M. , Steelman Lisa A. , Wildman Jessica L.
Published: June 2024

Purpose

The current study heeds prior calls to test the hypothesis that perceptions of inclusion mediate the relationship between inclusive practices and employee outcomes.

Design/methodology/approach

Using responses from 3,367 employees drawn from three time-separated surveys administered between 2020 and 2022 within a large retail fashion chain, structural equation modeling (SEM) was conducted to examine the mediating role of perceptions of inclusion connecting inclusion’s antecedents and outcomes. Exploratory multigroup SEM and relative weights analysis was conducted to examine the relative contribution of each antecedent of perceptions of inclusion across racial/ethnic groups.

Findings

We identified manager support, career support, organizational support, transparency, and employee recognition as antecedents of perceptions of inclusion, as well as work engagement, organizational commitment, and intent to stay as outcomes of perceptions of inclusion. Recognition indirectly relates to employee outcomes via perceptions of inclusion, but we did not find evidence of mediation for the other antecedents. Exploratory analyses suggest that career support and employee recognition are the most predictive antecedents of perceptions of inclusion overall. However, there are racial/ethnic group differences regarding which inclusive practices most contribute to perceptions of inclusion.

Originality/value

Results uncover several directions for future research and suggest that to truly make employees feel both included and unique at work, organizations should focus on supporting employees' career development goals and recognizing their valuable contributions.
Impact of organizational energy on digital transformation in healthcare services: the movement of human resources from inertia to flexibility
Authors: Ghonim Mohamed A. , Goda Abd El-Mohsen A. , Khashaba Nagi M. , Elsotouhy Mohamed M. , Khashan Mohamed A.
Published: June 2024

Purpose

While scholarly studies focus on the role of technology in digital transformation, an important direction of research still requires examining HR-related factors in this regard specifically. This study aims to analyze factors pertaining to human and organizational resources in the context of digital transformation within healthcare enterprises. The study examines the possible impacts of organizational energy (OE) and human resource flexibility (HRF) on digital transformation (DT). The study also seeks to investigate the influence of organizational inertia (OI) on the relationships being examined, according to the theory of change principles.

Design/methodology/approach

The empirical study used a survey method on 355 Mansoura University Hospitals employees, Egypt. The study data were analyzed using structural equations modeling with WarpPLS V. 8.0.

Findings

The results showed that all OE dimensions directly affected DT and HRF dimensions. Through HRF, OE indirectly affected DT. The study also found that all dimensions of OI negatively moderated the OE-DT and HRF-DT relationships. Based on the study's results, theoretical and practical implications were drawn.

Originality/value

This study develops a novel model to empirically investigate the quantitative relationships between OE, HRF, OI, and DT. This study provides an addition to understanding how human resources and organizational mechanisms work in technology-based experiments such as digital transformation and adds contributions in this regard to the health sector in particular.