bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective cross-sectional study to evaluate outcome of loco-regional flaps in head and neck reconstruction in Sudanese patients
Authors: Yassin Amin M. , Mohamed Momen M.
Published: April 2024

Introduction:

The soft tissue of the head and neck region poses both esthetic and functional aspects and must be retorted simultaneously, as any defect will be easy recognizable and will affect the quality of patient’s life. Reconstruction by local- regional flap still the most popular approach used and outcome also better than other options.

Objectives:

To assess the outcome of loco-regional flaps in head and neck reconstruction in Sudanese patients.

Patients and methods:

Retrospective cross-sectional, multicenteric study (Soba University Hospital, Khartoum North Teaching Hospital and an associated specialized hospital) – Khartoum, Sudan, 84 patients underwent head/neck reconstruction during the period from 2017 up to 2021 were included.

Results:

Out of 84 patients, 47.6% were female and 52.4% were male. The etiology of head and neck defects in the majority (69%) was neoplastic, and in 11.9% it was trauma. According to site of defect, in 23.8% of patients was Cheek unit, 21.4% was nasal site, and 16.7% was neck site. Surgery in 85.7% of patients were primary, while in 14.3 was delayed. Fasciocutaneous flaps were used in 64.3%, followed by myocutaneous flap in 28.6%; functional outcome was excellent in 61.9%, adequate in 35.7%, and was inadequate in only 2.4%. The majority of patients 66.2% did not develop any complications.

Conclusion:

Loco-regional flaps are ideally useful in covering head and neck defects. It has an acceptable esthetic and functional outcome in the majority of cases. It can be considered as a reliable option for reconstruction especially in resource constrained centers.
A Rapid Review on the Management of Constipation for Hospice and Palliative Care Patients
Authors: Gill Virpal , Badrzadeh Houman , Williams Sari , Crouch Nadia Masroor , Buga Sorin , Mooney Stefanie , Fasolino Tracy
Published: April 2024

Constipation is a distressing symptom that has a high prevalence in patients receiving hospice and palliative care services, particularly in cases of opioid use. A thorough assessment, root cause analysis, monitoring, and prophylactic approach are essential for symptom management and quality of life. This rapid review assessed studies published between 2018 and 2023 to identify strategies implemented by health care professionals to prevent and/or mitigate this distressing symptom. We identified 12 articles that addressed constipation in palliative and end-of-life settings and reported on the need for multifactorial management approaches with a focus on patient-centered care that includes the caregiver(s). Bedside nurses play a key role in assessing, identifying, and managing constipation. Proper documentation and communication with the interdisciplinary team help direct earlier intervention and ongoing awareness of constipation issues. Additional research is needed on specific tools and enhanced guidelines to ensure constipation is frequently addressed and preemptively managed.
Evolving Nursing Research Priorities
Authors: Cámpoli Marcela , Mulvey Tanya
Published: April 2024

The American Nurses Association Enterprise (ANA Enterprise) Research Advisory Council plays a vital role in bringing nursing voices together and shaping the dynamic landscape of nursing research. Historically, its priorities have revolved around 4 pivotal research priorities: advancing research capacity, promoting interprofessional collaboration, enhancing data structures and governance, and propelling practice-based nursing research. In a remarkable transition, the 2024 Research Priorities of the ANA Enterprise Research Advisory Council align with the vision and strategic goals of the ANA Enterprise. The Council now places emphasis on the intersection of the research priorities with 5 key areas crucial for “elevating the profession of nursing globally”: workforce development; advancing nurse well-being practices; deepening understanding of diversity, equity, inclusion, and belonging; expanding scope of practice; and measuring the value of nursing. This approach provides clear guidance for nursing research efforts, demonstrating a dedicated effort to harmonize the diverse voices within the nursing community. The objective is to shape a future where nursing research not only serves to inform practice but also enhances the overall value and impact of the nursing profession globally.
A Wake-Up Call to Address Nurse Fatigue
Authors: Weaver Susan H. , Wurmser Theresa A.
Published: April 2024

Research exploring differences in fatigue and sleep quality between day- and night-shift nurses highlights the urgent need for action to mitigate nurse fatigue. Nurses need to prioritize their sleep, and nurse leaders must take proactive measures such as providing education for all doing shiftwork, ensuring completion of job requirements during the shift, and creating a culture where nurses take their scheduled breaks.
Strategies and Interventions to Support Quality Outcomes in the Home Care Setting
Authors: Vleminckx Senne , Van Bogaert Peter , Daneels Katrien , Proost Ann , Sarens Stefaan , Haegdorens Filip
Published: April 2024

BACKGROUND

The relationship between the practice environment, empowerment, and outcomes such as quality of care, job satisfaction, and intent to stay has been extensively studied in healthcare settings, including hospitals and long-term care facilities. Research consistently demonstrates that a positive practice environment, characterized by supportive leadership, adequate resources, and opportunities for professional growth, are associated with better quality of care, increased job satisfaction, and higher intent to stay among healthcare professionals. Limited knowledge exists regarding the specific relationship between the practice environment, empowerment, and these outcomes within home care organizations.

OBJECTIVE

This study assesses the impact of strategies on nurse practice environment, social capital, decision latitude, workload, care quality, job satisfaction, and retention in a Belgian home healthcare organization.

METHODS

A longitudinal survey was conducted in a home healthcare organization, with data collected at 3 time points: baseline (T1) (2015), T2 (2018), and T3 (2021).

RESULTS

In T3, respondents reported significantly higher scores for departmental and general management compared with T1. The interventions led to significant improvements in social capital and decision latitude. Self-reported quality of care at the department level showed a significant increase, whereas no significant change was observed for quality of care during the last round.

CONCLUSION

The implementation of strategies and interventions as part of a broader healthcare transformation process had a positive impact. Improvements were observed in nurse-reported quality of care, job satisfaction, and intent to stay in nursing. These findings emphasize the effectiveness of the implemented measures in enhancing nursing practice and creating a positive work environment. Continuous efforts to implement and evaluate such strategies are essential for enhancing the satisfaction and retention of nursing teams within healthcare organizations.
Examining the Effect of Entrepreneurial Leadership on Nursing Team Creativity in New Hospitals
Authors: Zhou Jing , Gong Jing , Suen Lorna Kwai Ping , Yang Binxu , Zhang Xia , Chan Shun , De Jesus David Hali , Tang Jin
Published: April 2024

AIMS

This research examines the relationship between entrepreneurial leadership and nursing team creativity in new hospitals and introduces innovation climate, creative self-efficacy, team psychological safety, and knowledge sharing as mediating variables.

METHODS

This cross-sectional study sampled 833 nurses from 2 new hospitals in Guizhou Province, China. They completed a questionnaire on entrepreneurial leadership, nursing team creativity, innovation climate, creative self-efficacy, team psychological safety, and knowledge sharing. Data were analyzed using structural equation modeling.

RESULTS

Entrepreneurial leadership positively influenced nursing team creativity. Innovation climate, creative self-efficacy, team psychological safety, and knowledge sharing mediated the relationship between entrepreneurial leadership and nursing team creativity in new hospitals.

CONCLUSIONS

This study confirmed the significant role of innovation climate, creative self-efficacy, team psychological safety, and knowledge sharing in mediating the relationship between entrepreneurial leadership and nursing team creativity through empirical analysis.
An Effective Academic Medical Center–Based Strategy to Enhance Diversity Among Nurse Researchers
Authors: Banister Gaurdia , Goldman Julie , Jones Dorothy A. , Looby Sara E.
Published: April 2024

The Connell-Jones Endowed Chair Diversity Nursing Research Scholars Program was created to promote engagement in nursing research and scholarship among nurses of color. Preliminary evaluation suggests that the program was widely beneficial, resulting in enrollment in doctoral education for some. Establishing opportunities that promote exposure and participation in nursing research and scholarship among nurses of color helps cultivate cohorts of diverse nurses armed to address health disparities through the advancement of nursing knowledge.
Delays in sexual health care among patients attending New York City Sexual Health Clinics during the COVID-19 pandemic, March 2020 to February 2021
Authors: Tang Jennifer , Crawley Addie , Jamison Kelly , Wong Athena , Eng Stephen , Zhang Caroline , Navia Isabella , Cubas Carlos , Pathela Preeti
Published: April 2024

Background

Public health emergencies can lead to reduced or suspended services in sexual health clinics (SHCs), raising questions about optimal ways to maintain access to care. We examined changes in sexual behaviors, HIV pre-exposure prophylaxis (PrEP) use, telehealth preference, and correlates of delayed sexual health care among patients attending New York City (NYC) publicly funded SHCs during the COVID-19 pandemic.

Methods

470 patients from four SHCs (July-September 2021) completed a self-administered survey that collected data on access to sexual health care, overall and over three distinct time periods [Spring 2020 (COVID-19 wave 1), Summer 2020, Fall 2020/Winter 2021 (COVID-19 wave 2)]. We used log-binomial models to examine factors associated with delayed sexual health care.

Results

Participants reporting multiple in-person sexual contacts increased from 28% to 57% (P < 0.0001) between the first and second wave. Almost half of participants (35/72) taking HIV PrEP cited decreased use. Over 90% (423/460) of participants preferred in-person clinic visits over telehealth. Overall, delays in routine and urgent sexual health care were reported by 34% (129/375) and 12% (46/373) of participants, respectively. More men who have sex with men (MSM) and transgender/gender non-conforming/nonbinary (TGNCNB) individuals experienced delayed care compared with women [MSM: aPR 1.43 (95% CI, 1.00-2.03); TGNCNB: 1.67 (1.04-2.69)]. Compared with participants who primarily sought sexual health care from private providers, those who primarily used SHCs experienced significantly more delayed care [1.72 (1.14-2.59)].

Conclusions

Delays in sexual health care access can have serious implications for certain patient populations. Additional resources are needed to maintain access to sexual health clinic services.
A Novel Macroglossia Severity Index for Beckwith-Wiedemann Syndrome
Authors: Romeo Dominic J. , Banala Manisha , Wu Meagan , Ng Jinggang J. , Massenburg Benjamin B. , George Andrew , DeMarchis Madison , Liao Eric C. , Kalish Jennifer M. , Taylor Jesse A.
Published: April 2024

Objective/ Summary Background Data:

We propose the first classification scheme for macroglossia in patients with Beckwith-Wiedemann Syndrome (BWS), the BWS Index of macroGlossia (BIG).

Methods:

Patients with molecularly confirmed BWS seen from 2004-2023 were included to develop this system. Relationships among BIG scores, tongue reduction surgery, BWS clinical score, percent mosaicism, and polysomnography findings were examined.

Results:

Patients were classified from BIG0 to BIG3. BIG0 includes those without macroglossia; BIG1 includes those with macroglossia not protruding beyond the teeth/alveolus; BIG2 includes those with tongue protrusion past the teeth/alveolus to the lips but that can be contained within the mouth; and BIG3 includes those with tongues that protrude beyond the teeth/alveolus and lips but that cannot be closed within the mouth. Of the 459 patients with molecularly confirmed BWS, 266 (58.0%) patients were scored. One hundred and eleven (41.7%) were BIG0, 44 (16.5%) were BIG1, 90 (33.8%) were BIG2, and 21 (7.9%) were BIG3. As scores increased, patients had an increased incidence of tongue reduction surgery (BIG0: 0% versus BIG1: 20.5% versus BIG2: 51.1% versus BIG3: 100%; r=0.66, P<0.01). Higher BIG scores were associated with elevated BWS clinical scores (r=0.68, P<0.01) and increased tissue mosaicism (r=0.50, P<0.01) as well as trends towards worse obstructive apnea-hypopnea indices (r=0.29, P=0.02) and lower SpO2 nadirs (r=−0.29, P=0.02).

Conclusion:

In this large series of patients with Beckwith-Wiedemann Syndrome, increased BIG score correlates with undergoing tongue reduction surgery and increased phenotypic severity. Adoption of the BIG scoring system may facilitate communication and risk stratification across institutions.
The Relevance of Differential Assessment Between Campimetry Deficit and Neglect in Hospitalized Neurologic Patients
Authors: Garella Paolo , Battaglino Andrea , Gargano Stefano , Alonso-Pérez José Luis , Villafañe Jorge Hugo
Published: April 2024

Background:

This study investigates the clinical impact of visual system diseases and neuropsychological deficits on individualized rehabilitation programs for hospitalized neurologic patients. This study aimed to evaluate the clinical impact of visual system diseases and neuropsychological deficits on individualized rehabilitation programs for hospitalized neurologic patients.

Methods:

An observational study was conducted on adult inpatients with neurologic disorders who were admitted to the neurology ward between February 2022 and January 2023. These patients underwent comprehensive multidisciplinary assessments as well as clinical orthoptic evaluations. We collected data pertaining to demographics, medical history, diagnoses, and rehabilitation reports. All participants met specific eligibility criteria, including age, cognitive status, and clinical stability.

Results:

Initially, 120 patients, 68 ±13 years old, were included in the full cohort. Subsequently, after excluding patients with low interview reliability, those lacking campimetry defects, or those solely presenting neglect, a final cohort of 7 patients remained for qualitative analysis. This final group exhibited a broad age range, predominantly had vascular diagnoses, and experienced prolonged hospital stays. These patients were notable for the presence of campimetry disorders and frequently faced challenges associated with spatial neglect.

Conclusions:

Visual system diseases and neuropsychological deficits significantly impact the planning and execution of rehabilitation programs for hospitalized neurologic patients. A multidisciplinary approach, with the orthoptist's expertise, is essential to address visual impairments, improving the quality of life and functional outcomes of stroke survivors.
Assessing the Influence of Unstable Footwear on Lower Limb Lymphedema
Authors: Robledo-Donascimento Yolanda , López-Mesa Mario Manuel , Rubio-Alonso Margarita , Varela-Donoso Enrique , Abuín-Porras Vanesa , Romero-Morales Carlos , de-la-Cueva-Reguera Mónica , Villafañe Jorge Hugo
Published: April 2024

Introduction:

Unstable shoes may benefit lower limb lymphedema patients by reducing foot volume and relieving symptoms.

Objective:

The objective of this study was to evaluate and compare the effectiveness of unstable shoes versus conventional sports shoes in managing lower limb lymphedema, focusing on changes in foot volume, circumference, and symptom relief.

Methods:

We conducted an 8-week clinical trial, recruiting patients with lower limb lymphedema. Participants were divided into 2 groups: one using unstable shoes and the other using conventional sports shoes. Measurements of foot volume and circumference were taken at the beginning and end of the trial. Additionally, participants were asked to report any changes in leg cramps and paraesthesia during the study period.

Results:

The results indicated a nonstatistically significant tendency toward a decrease in foot volume and circumference in the intervention group using unstable shoes. In contrast, the control group using conventional sports shoes showed a tendency toward an increase in foot volume and a statistically significant increase in foot circumference. Moreover, participants in the unstable shoes group reported a decrease in leg cramps and paraesthesia, indicating potential symptom relief.

Conclusions:

This study suggests that unstable shoes have the potential to offer benefits to individuals with lower limb lymphedema, particularly in terms of foot volume reduction and symptom relief. The use of unstable shoes may be suitable for activities such as walking and extended periods of standing. However, further research is necessary to explore their full potential and effectiveness in managing lymphedema symptoms comprehensively.
Multicomponent Exercise Program to Avoid Productivity Loss Due to COVID-19
Authors: Artiles-Sánchez Justo , Fernández-Carnero Josué , Sánchez-Romero Eleuterio A. , Cuenca-Zaldívar Juan Nicolás , Martínez-Lozano Pedro , Meléndez-Oliva Erika , Alonso-Perez José Luís , Villafañe Jorge Hugo
Published: April 2024

Objective:

To evaluate and quantify the mitigation of productivity deficits in individuals recovering from post-COVID-19 conditions by implementing a multicomponent exercise program (MEP).

Methods:

Thirty-nine post-COVID-19 patients meeting specific criteria participated in a 7-week intervention program involving cycloergometer interval training, strength exercises, and respiratory physiotherapy. Follow-up assessments occurred 2 weeks post-intervention and 23 months later via telephone interviews. The study computed the average avoided loss of productivity to estimate indirect costs.

Results:

Over 2 years, 51.4% had persistent symptoms and 48.7% reported complex issues. Age differences were observed between retired and employed individuals. Multinomial regression revealed a 91.849 times higher likelihood of simple signs in employed individuals and a 1.579 times higher likelihood of being older in retirees. Simple symptoms were associated with a 90 000 times higher likelihood of returning to work. Sensitivity analysis indicated potential productivity gains from €117 955 to €134 004 per patient over a 4-year horizon.

Conclusion:

The MEP is a safe and effective post-COVID recovery intervention, notably aiding workforce reintegration for individuals with simple signs. Patients with such signs were significantly more likely to return to work, highlighting potential productivity gains and emphasizing the need for further research on the program's cost-effectiveness and broader societal benefits.
Variability of pMGA/vlhA sequences among Mycoplasma gallisepticum field strains isolated from laying hens and their deformed eggs.
Authors: Maya-Rodríguez Linda , Gómez-Verduzco Gabriela , Trigo-Tavera Francisco J. , Moreno-Fierros Leticia , Miranda-Morales Rosa Elena
Published: April 2024

Mycoplasmosis, attributed to Mycoplasma gallisepticum, poses a significant challenge to poultry farming, leading to substantial economic losses and persistent infections within flocks. This bacterium harbors various surface proteins that are crucial for the adhesion, transporter activity, and evasion of the host immune response, facilitating its pathogenicity. One such key surface lipoprotein, referred to as pMGA or vlhA hemagglutinin, plays a pivotal role in adhesion processes. In this study, the clonal regions pMGA1.2 and pMGA1.3, as reported by Markham (M83178.1), were investigated to elucidate differences or similarities in the whole DNA sequences of Myc. gallisepticum field strains. The aim was to analyze sequence diversity within this region. Six internal primers were designed to amplify the target sequence, and isolates were obtained from both eggs and chickens sourced from laying hen flocks. Identification revealed 17 strains of Myc. gallisepticum and four strains of Myc. synoviae, which were confirmed through the mgc2 and 16S rRNA genes, respectively. Positive and negative controls were established using the MGS6 and MSWUV1853 strains. Amplification results indicated a higher frequency of amplification proximal to the C-terminal region, with segments 4 (33.3%) and 6 (27.8%) being the most prevalent. Notably, none of the field strains exhibited the same amplification pattern as MGS6, and none of the strains characterized as Myc. synoviae amplified any primer set.
Upon translation, the amino acid sequences from segments 4 and 6 were found to be compatible with conserved sequences within the Myco_haema protein domains of the genus Mycoplasma, specifically corresponding to Q7NAP3_MYCGA VlhA.3.04. The observed homology suggests a potential genetic transfer, while the variability identified in the pMGA or vlhA gene region of the field strains may have significant implications for protection against Myc. gallisepticum infection in chickens.
Effect of motivational interviewing on lifestyle modification among patients with hypertension attending the family medicine clinics of Irrua Specialist Teaching Hospital, Irrua, Nigeria – A randomized controlled trial (MILMAPH Study)
Authors: Oseni Tijani Idris Ahmad , Oku Afiong Oboko , Monye Ifeoma N , Ahmed Sulaiman Dazumi , Duke Roseline Ekanem , Otaigbe Osahon , Udonwa Ndifreke Ekpo
Published: April 2024

Background

Lifestyle modification has been shown to improve blood pressure (BP) control, but its practice is poor among patients with hypertension. Thus, measures that would help patients with hypertension achieve positive lifestyle modification would improve BP control. The study aimed to determine the effect of motivational interviewing on lifestyle modification and blood pressure control among patients with hypertension attending the Family Medicine Clinics of Irrua Specialist Teaching Hospital (ISTH), Irrua, Nigeria.

Methods

The study was a randomised control trial (PACTR202301917477205) of 250 hypertensive adults between 18 and 65 years presenting to the Family Medicine Clinics of ISTH randomised into intervention and control groups. Those in the intervention group were given monthly motivational interviewing (MI) on lifestyle modification in addition to standard care for the management of hypertension while those in the control group got standard care only for 6 months. Both groups were assessed at baseline and 6 months. Data was analysed with Stata version 17 (StataCorp LLC) with level of significance at 0.05. Primary outcome was lifestyle modification while secondary outcome was BP control both at 6 months.

Results

The age of the participants ranged from 24 to 65 years with a mean age of 51.5 ± 10.0 years. The blood pressure control at baseline was 24%. At the end of the six-month study, there was a statistically significant improvement in the lifestyle pattern of the intervention group compared to control except smoking in which the difference was not statistically significant (p=0.150). Blood pressure control significantly improved from 24% at baseline to 48% post-intervention (p=0.014).

Conclusion

The study found a significant positive association between motivational interviewing and lifestyle modification. The study also found a significant improvement in blood pressure control following motivational interviewing. There is a need to incorporate motivational interviewing into the management of hypertension for better outcomes.
Cytosolic S100A8/A9 promotes Ca2+supply at LFA-1 adhesion clusters during neutrophil recruitment
Authors: Napoli Matteo , Immler Roland , Rohwedder Ina , Lupperger Valerio , Pfabe Johannes , Gonzalez Pisfil Mariano , Yevtushenko Anna , Vogl Thomas , Roth Johannes , Salvermoser Melanie , Dietzel Steffen , Slak Rupnik Marjan , Marr Carsten , Walzog Barbara , Sperandio Markus , Pruenster Monika
Published: April 2024

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions. Mechanistically, genetic deletion of S100A9 in mice (Mrp14−/−, functionalS100a8/a9−/−) caused dysregulated Ca2+signatures in activated neutrophils resulting in reduced Ca2+availability at the formed LFA-1/F-actin clusters with defective β2integrin outside-in signaling during post-arrest modifications. Consequently, we observed impaired cytoskeletal rearrangement, cell polarization and spreading, as well as cell protrusion formation inMrp14−/−compared to WT neutrophils, makingMrp14−/−cells more susceptible to detach under flow, thereby preventing efficient neutrophil recruitment and extravasation into inflamed tissue.

One-sentence summary

intracellular S100A8/A9 is indispensable for firm leukocyte adhesion under flow
Maize stigmas react differently to self-/cross-pollination and fungal invasion
Authors: Begcy Kevin , Mondragón-Palomino Mariana , Zhou Liang-Zi , Seitz Patricia-Lena , Márton Mihaela-Luiza , Dresselhaus Thomas
Published: April 2024

During sexual reproduction in flowering plants, rapid tip-growing pollen tubes travel from the stigma inside the maternal tissues of the pistil towards ovules. In maize, the stigma is highly elongated forming thread-like strands known as silks. Only compatible pollen tubes are supported to penetrate and to grow successfully through the transmitting tract of the silk to reach the ovules. Like pollen, fungal spores germinate at the surface of silks and generate tube-like structures (hyphae) penetrating silk tissue. To elucidate commonalities and differences between silk responses to various invaders, we compared growth behavior of the various invaders as well as the silk transcriptome after self-pollination, cross-pollination and infection using two different fungi. We report that self-pollination triggers especially senescence genes, while incompatible pollination usingTripsacum dactyloidesleads to downregulation of rehydration genes, microtubule and modulation of cell wall-related genes explaining slower pollen tube growth and their arrest. Invasion by the ascomyceteFusarium graminearumtriggers numerous defense responses including the activation of monolignol biosynthesis and NAC as well as WRKY transcription factor genes, while responses to the basidiomyceteUstilago maydisare generally much weaker. Cell wall and phytoalexin biosynthesis pathways were selected as examples to demonstrate usability of the data sets provided.

One sentence summary

Data sets are provided and analyzed to elucidate how maize stigmas (silks) respond to different biotic invaders including own and alien pollen tubes as well as hyphae of two different fungi.
The splicing factor kinase SRPK1 is a therapeutic target for Peripheral Vascular Disease
Authors: Bhalla Sohni Ria , Wahid Mussarat , Amartey Jason O , Zawia Amira , Riu Federica , Gao Yizhuo , Agrawal Jyoti , Lynch Amy P , Machado Maria JC , Hawtrey Tom , Kikuchi Ryosuke , Green Kathryn R , Teboul Lydia , Allen Claire , Blackley Zoe , Rajaji Keerthana , Marsden Daisy , Batson Jennifer , Harper Steven J , Oltean Sebastian , Amoaku Winfried , Benest Andrew V , Morris Jonathan C , Braithwaite Bruce , Bates David O
Published: April 2024

Introduction

In peripheral arterial disease (PAD) anti-angiogenic VEGF-A165b isoform overexpression in monocytes contributes to impaired collateralisation. Serine-arginine protein-kinase-1 (SRPK1) regulates VEGF splicing. To determine whether SRPK1 controlled monocytic VEGF, impairing collateralisation, we investigated SRPK1 inhibition and monocyte-specific knockout in mouse models of and in human monocytes from PAD.

Methods

VEGF-A165b activity was measured by co-culture of PAD patients’ monocytes with endothelial cells with SRPK1 inhibition. Mice with impaired revascularisation due to soluble-frizzled-related-protein-5 knockout (Sfrp5-/-), monocyte-specific Wnt5a gain-of-function (LysM-Wnt5aGOF), or obese mice on a high-fat high-sucrose (HF/HS) diet were subjected to femoral artery ligation and treated with SRPK1 inhibitor. We generated an SRPK1 conditional knockout and crossed it with monocyte-specific (LysM-Cre) driver line to specifically knockout SRPK1 in monocyte lineages. Blood flow was measured by Laser Speckle Imaging before, and for 28 days after surgery.

Results

Monocytes from PAD patients significantly inhibited endothelial cell migration, which was reversed by an anti-VEGF-A165b antibody. Surprisingly, migration was stimulated by SRPK1 inhibition, switching splicing from VEGF-A165b to VEGF-A165a. In Sfrp5-/-, LysM-Wnt5aGOFand HF/HS mouse models of PAD, blood flow was improved by SRPK1 inhibition. Impaired revascularisation in LysM-Wnt5aGOFmice was rescued in LysM-Wnt5aGOF:SRPK1MoKOmice, which had a phenotypic shift towards M2 macrophages. Impaired blood flow recovery was also rescued in obese-SRPK1MoKOmice.

Conclusion

VEGF splicing in monocytes is regulated differently from VEGF splicing in epithelial or cancer cells suggesting that control of splicing is dependent on cell type and/or environment. SRPK1 inhibition enhances collateralisation in mice, and in humanin vitromodels of monocyte-dependent impaired angiogenesis.

New and Noteworthy

A novel potential treatment for peripheral arterial disease (PAD) is described. Inhibition of SRPK1, or knockout in monocytes, induces angiogenesis by preventing splicing to anti-angiogenic VEGF (VEGF-A165b) in patients and animal models. In PAD, monocyte splicing control is different from other cell types and SRPK1 inhibition by drug like compounds can alter macrophage phenotype and reverse PAD in mice using a new cell specific SRPK1-LoxP mouse.
Outcome of community onset severe sepsis, Sepsis-3 sepsis, and bacteremia in Sweden – a prospective population-based study
Authors: Ljungström Lars , Andersson Rune , Jacobsson Gunnar
Published: April 2024

Background

Register-based studies are common in sepsis epidemiology. Chart review is considered gold standard but is time consuming. This is one of few such studies.

Methods

In a 9-month prospective and consecutive study conducted in 2011-12, chart review was used to investigate outcomes in patients with severe sepsis, Sepsis-3 sepsis, and bacteremia in a population of 256,700 inhabitants in southwest Sweden. All adult patients aged ≥18 years admitted to hospital and given intravenous antibiotic treatment within 48 hours were evaluated, N=2,196. Cohort mortality was calculated up to 10 years after admission.

Results

Among 2,072 adults with any infection, 429 patients had severe sepsis of which 59 had septic shock. The 28-day case fatality rate (CFR) was 25%, 41% in those with septic shock. Sepsis-3 sepsis was diagnosed in 1,299 patients. The 28-day CFR was 12%. Among the 1,299, 393 also had severe sepsis. In 906 patients with Sepsis-3 sepsis but not severe sepsis, the 28-day CFR was 6%. For both sepsis definitions, the 28-day CFR increased 10-fold between the youngest and the oldest age groups. Age >75 years, and renal dysfunction were the strongest independent risk factors for 28-day case fatality. Bacteremia occurred in 283/2,072 (13%) patients. The 28-day CFR was 13% overall, 25% in severe sepsis and 4% in non-severe sepsis. Even 10 years after admission, the mortality rate was higher in sepsis patients by either definition.

Conclusions

The 28-day case fatality rate (CFR) in patients with Sepsis-3 sepsis, 12%, is the result of a large group of patients with a low 28-day CFR, 6%, camouflaging a group with severe sepsis and a high 28-day CFR, 25%. Age >75 years is an independent risk factor for case fatality. The 28-day CFR in patients with bacteremia is a function of severe sepsis, not bacteremiaper se. Even after ten years, mortality is increased in both sepsis groups.
Personality traits vary in their association with brain activity across situations
Authors: Hardikar Samyogita , McKeown Brontë , Turnbull Adam , Xu Ting , Valk Sofie L. , Bernhardt Boris C. , Margulies Daniel S. , Milham Michael P. , Jefferies Elizabeth , Leech Robert , Villringer Arno , Smallwood Jonathan
Published: April 2024

Human cognition supports complex behaviour across a range of situations, and traits (such as personality) influence how we react in these different contexts. Although viewing traits as situationally grounded is common in social sciences it is often overlooked in neuroscience. Often studies focus on linking brain activity to trait descriptions of humans examine brain-trait associations in a single task, or, under passive conditions like wakeful rest. These studies, often referred to as brain wide association studies (BWAS) have recently become the subject of controversy because results are often unreliable even with large sample sizes. Although there are important statistical reasons why BWAS yield inconsistent results, we hypothesised that results are inconsistent because the situation in which brain activity is measured will impact the power in detecting a reliable link to a specific trait. To examine this possibility, we performed a state-space analysis in which tasks from the Human Connectome Project (HCP) were organized into a low-dimensional space based on how they activated different large-scale neural systems. We examined how individuals’ observed brain activity across these different contexts related to their personality. Our analysis found that for multiple personality traits (including Agreeableness, Openness to Experience and Conscientiousness) stronger associations with brain activity emerge in some tasks than others. These data establish that for specific personality traits there are situations in which reliable associations with brain activity can be identified with greater accuracy, highlighting the importance of context-bound views of understanding how brain activity links to trait variation in human behaviour.

Significance statement

As a species humans act efficiently in many contexts, however, as individuals our personality makes us more specialised in some situations than others. This “if-then” view of personality is widely accepted in the social sciences but is often overlooked in neuroscience. Here we show adopting a situationally bound view of human traits provides more meaningful descriptions of a brain-trait associations than are possible in traditional brain wide association studies (BWAS) that measure brain activity in a single situation. Our results demonstrate multiple personality traits (including Agreeableness, Openness to Experience and Conscientiousness) show stronger associations with brain activity in some tasks than others, explaining why studies focusing on changes in brain activity at rest can lead to weak or contradictory results.
The geometry of prey capture in praying mantis forelegs
Authors: Dan Shu D. , Taylor Danielle S. , Yockey Jaime , Svenson Gavin J. , Martin Joshua P.
Published: April 2024

The form of an animal’s limbs has to balance multiple functions: locomotion, grasping, climbing, and jumping, among others. For cryptic animals, especially those that resemble elements of their habitat like sticks or grasses, the limbs may also be modified to enhance the camouflage. The performance of a limb in one category may require a tradeoff, reducing performance in another category. Praying mantises provide a diverse group of insects who all use their forelegs for one function, capturing prey, while some species use them as part of their camouflage. Here we use a large database of images of mantis species to capture the variation in morphology across the order, and to calculate the largest prey that their forelegs can hold. We find that the length and thickness of the femur and the length of the tibia comprise most of the variability across species. The majority of species have similar foreleg morphology, with two large groups extending into areas of the morphospace with thicker or thinner forelegs. A geometric relationship between dimensions of the foreleg and the optimal prey diameter maps directly onto the variability across species determined by principal components analysis; legs with thinner femurs and shorter tibia can’t hold large prey, and the distribution of the species across the morphospace follows the gradient of optimum prey size. These results suggest that some species trade ability to grasp larger prey for benefits including crypsis, and the praying mantises are an ideal system for studying morphological and functional variation in limbs.
Sex differences in sensitivity to dopamine receptor manipulations of risk-based decision making in rats
Authors: Wheeler Alexa-Rae , Truckenbrod Leah M. , Boehnke Adrian , Orsini Caitlin A.
Published: April 2024

Risky decision making involves the ability to weigh risks and rewards associated with different options to make adaptive choices. Previous work has established a necessary role for the basolateral amygdala (BLA) in mediating effective decision making under risk of punishment, but the mechanisms by which the BLA mediates this process are less clear. Because this form of decision making is profoundly sensitive to dopaminergic (DA) manipulations, we hypothesized that DA receptors in the BLA may be involved in risk-taking behavior. To test this hypothesis, male and female Long-Evans rats were trained in a decision-making task in which rats chose between a small, safe food reward and a larger food reward that was associated with a variable risk of footshock punishment. Once behavioral stability emerged, rats received intra-BLA infusions of ligands targeting distinct dopamine receptor subtypes prior to behavioral testing. Intra-BLA infusions of the dopamine D2 receptor (D2R) agonist quinpirole decreased risk taking in females at all doses, and this reduction in risk taking was accompanied by an increase in sensitivity to punishment. In males, decreased risk taking was only observed at the highest dose of quinpirole. In contrast, intra-BLA manipulations of dopamine D1 or D3 receptors (D1R and D3R, respectively) had no effect on risk taking. Considered together, these data suggest that differential D2R sensitivity in the BLA may contribute to the well-established sex differences in risk taking. Neither D1Rs nor D3Rs, however, appear to contribute to risky decision making in either sex.
Multisensory integration in Anopheles mosquito swarms: The role of visual and acoustic information in mate tracking and collision avoidance
Authors: Gupta Saumya , Cribellier Antoine , Poda Serge B , Roux Olivier , Muijres Florian T , Riffell Jeffrey A
Published: April 2024

Male mosquitoes form aerial aggregations, known as swarms, to attract females and maximize their chances of finding a mate. Within these swarms, individuals must be able to recognize potential mates and navigate the dynamic social environment to successfully intercept a mating partner. Prior research has almost exclusively focused on the role of acoustic cues in mediating the ability of male mosquitoes to recognize and pursue flying females. However, the role of other sensory modalities in this behavior has not been explored. Moreover, how males avoid collisions with one another in the dense swarm while pursuing females remains poorly understood. In this study, we combined free-flight and tethered flight simulator experiments to demonstrate that swarming Anopheles coluzzii mosquitoes integrate visual and acoustic information to track conspecifics and avoid collisions. Our tethered experiments revealed that acoustic stimuli gated mosquito steering responses to visual objects simulating nearby mosquitoes, especially in males that exhibited attraction to visual objects in the presence of female flight tones. Additionally, we observed that visual cues alone could trigger changes in wingbeat amplitude and frequency of mosquitoes. These findings were corroborated by our free-flight experiments, which revealed that mosquitoes modulate their flight responses to nearby conspecifics in a similar manner to tethered animals, allowing for collision avoidance within swarms. Together, these results demonstrate that both males and females integrate multiple sensory inputs to mediate swarming behavior, and for males, the change in flight kinematics in response to multimodal cues allows them to simultaneously track females while avoiding collisions.
Hypoactivation of ventromedial frontal cortex in major depressive disorder: an MEG study of the Reward Positivity
Authors: Pirrung Christopher J.H. , Singh Garima , Hogeveen Jeremy , Quinn Davin , Cavanagh James F.
Published: April 2024

Background

The Reward Positivity (RewP) is sensitive and specific electrophysiological marker of reward receipt. These characteristics make it a compelling candidate marker of dysfunctional reward processing in major depressive disorder. We previously proposed that the RewP is a nexus of multiple aspects of reward variance, and that a diminished RewP in depression might only reflect a deficit in some of this variance. Specifically, we predicted a diminished ventromedial contribution in depression in the context of maintained reward learning.

Methods

Here we collected magnetoencephalographic (MEG) recordings of reward receipt in 43 individuals with major depressive disorder (MDD group) and 38 healthy controls (CTL group). MEG allows effective source estimation due to the absence of volume conduction that compromises electroencephalographic recordings.

Results

The MEG RewP analogue was generated by a broad set of cortical areas, yet only right ventromedial and right ventral temporal areas were diminished in MDD. These areas correlated with a principal component of anhedonia derived from multiple questionnaires. Compellingly, BA25 was the frontal region with the largest representation in both of these effects.

Conclusions

These findings not only advance our understanding underlying the computation of the RewP, but they also dovetail with convergent findings from other types of functional source imaging in depression, as well as from deep brain stimulation treatments. Together, these discoveries suggest that the RewP may be a valuable marker for objective assessment of reward affect and its disruption in major depression.
Cytosolic Class I J-domain proteins aid mitochondrial protein import and influence homeostasis inArabidopsis thaliana
Authors: Lal Silviya S. , Neha  , Yadav Yadvendradatta Rajendra Prasad , P. Sreehari , Verma Amit K. , Sahi Chandan
Published: April 2024

Mitochondrial homeostasis heavily relies on import of numerous nuclear encoded proteins. Multiple chaperone machineries operate at the cytosolic and mitochondrial side of the bilayer to ensure the efficacy of this process. While the mechanisms and components involved in translocation of polypeptides into the mitochondria are known in great detail, the cytosolic events of mitochondrial protein import are poorly understood in plants. This study explores the role of two cytosolic Class I J-domain proteins (JDPs), atDjA1 and atDjA2, in mitochondrial homeostasis inArabidopsis thaliana. We show that atDjA1 and atDjA2 uniquely interacted with outer mitochondrial surface receptors, Tom9, Metaxin, and OM64, which guide the import of numerous mitochondrial precursors. Knockout of atDjA1 or atDjA2 impeded seed germination under multiple abiotic stress conditions, with atDjA1 mutant being more sensitive. Both the mutants demonstrated decreased respiratory rates and enhanced accumulation of reactive oxygen species (ROS), indicating compromised mitochondrial function. Further, knockout of atDjA1 resulted in a significant decline in the number of active mitochondria as well as import of MTS-GFP. While atDjA2 mutants did not show a reduction in mitochondrial number, both the mutants had an activated mitochondrial retrograde signaling (MRS) further underscoring compromised mitochondrial homeostasis in these mutants. Our findings suggest that evolutionarily conserved cytosolic Class I JDPs preserve mitochondrial homeostasis by targeting specific receptors on the outer mitochondrial surface, facilitating the import of cytosolically synthesized mitochondrial precursors inArabidopsis thaliana.
Nanodisc reconstitution and characterization of amyloid-β precursor protein C99
Authors: Krishnarjuna Bankala , Sharma Gaurav , Hiiuk Volodymyr M , Struppe Jochem , Nagorny Pavel , Ivanova Magdalena I , Ramamoorthy Ayyalusamy
Published: April 2024

Amyloid precursor protein (APP) plays a pivotal role in the pathology of Alzheimer’s disease. Since the fragmentation of the membrane-bound APP that results in the production of amyloid-beta peptides is the starting point for amyloid toxicity in AD, it is important to investigate the structure and dynamics of APP in a near-native lipid-bilayer environment. However, the reconstitution of APP into a stable/suitable membrane-mimicking lipid environment is a challenging task. In this study, the 99-residue C-terminal domain of APP is successfully reconstituted into polymer nanodiscs and characterized using size-exclusion chromatography, mass spectrometry, solution NMR, and magic-angle spinning solid-state NMR. In addition, the feasibility of using lipid-solubilizing polymers for isolating and characterizing APP in nativeE. colimembrane environment is demonstrated.
Long non-coding RNAs regulate the expression of cell surface receptors in plants
Authors: Bhasin Hemal , Khan Hasna , Kileeg Zachary , Mott G. Adam
Published: April 2024

Plants are exposed to a variety of growth, developmental, and environmental cues during their lifespan. To survive and thrive, plants have developed sophisticated ways of responding to these signals that involve regulation at the transcriptional, post-transcriptional, translational, and post-translational levels. Leucine-rich repeat receptor-like kinases are the largest family of receptor-like kinases in plants and respond to a range of external and internal stimuli. They act as crucial regulators of plant growth, development, and immunity. To fully understand LRR-RLK function, it is essential to understand how their expression is regulated under different conditions. While there have been numerous studies on post-translational regulation of LRR-RLKs through phosphorylation and ubiquitination, there is little known about the mechanisms of transcriptional and post-transcriptional regulation of LRR-RLKs. In this study, we show that natural antisense transcript long non-coding RNAs are central regulators of LRR-RLK expression at the transcriptional and post-transcriptional levels. LRR-RLK genes are almost universally associated with cis-NATs and we confirm cis-NAT expressionin plantausing strand-specific RT-PCR. We leverage several well-studied LRR-RLKs to demonstrate that cis-NATs regulate LRR-RLK expression and function. For cis-NATs to fine-tune LRR-RLK expression, their expression and regulatory activity must be tightly controlled and cell autonomous. Using a combination of GUS reporter assays and tissue-specific promoters, we provide evidence that cis-NATs have these characteristics, positioning them as key regulators of LRR-RLK function. We also demonstrate that the association of LRR-RLK genes with cis-NATs is conserved across much of plant evolution, suggesting that this previously unexplored regulatory mechanism serves an important and ancient purpose.