bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for hypertension in adults: protocol for evidence reviews to inform a Canadian Task Force on Preventive Health Care guideline update
Authors: Shaver Nicole , Beck Andrew , Bennett Alexandria , Wilson Brenda J. , Garritty Chantelle , Subnath Melissa , Grad Roland , Persaud Navindra , Thériault Guylène , Flemming Jennifer , Thombs Brett D. , LeBlanc John , Kaczorowski Janusz , Liu Peter , Clark Christopher E. , Traversy Gregory , Graham Eva , Feber Janusz , Leenen Frans H. H. , Premji Kamila , Pap Robert , Skidmore Becky , Brouwers Melissa , Moher David , Little Julian
Published: January 2024

Purpose

To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews.

Methods

To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case–control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes.

Discussion

The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older.

Systematic review registration

This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).
The efficacy of tixagevimab/cilgavimab (Evusheld) in prophylaxis and treatment of COVID-19 in immunocompromised patients: a systematic review and meta-analysis
Authors: Glhoom Shaymaa , Fergany Aya , El-Araby Dina , Abdelkhalek Asmaa A. , Gomaa Asmaa , Zayed Eman O. , Abd-ElGwad Mohamed
Published: January 2024

Background

During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efficacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophylaxis for higher-risk individuals to reveal if there is a significant difference in efficacy between those two doses of the drug.

Methods

In this study, electronic databases (PubMed, Web of Science core collection, Scopus, and Cochran) were investigated for articles up to 31/12/2022 in English using a well-established search strategy. We included studies conducted in immunocompromised patients (aged ≥ 12 years) (WHO) received Evusheld as prophylaxis or treatment for COVID-19. After excluding studies inconsistent with the selection criteria, 24 were involved, 22 of which were included in the meta-analysis. We analyzed the data by using RevMan 5.4 program software.

Results

In the double-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed no significant difference in the COVID-19 infection rate, mortality rate, or needed hospitalization rate compared with the dose of 300 mg (p = 0.13, p = 0.29, and p = 0.25, respectively). In the single-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed a significant decrease in the COVID-19 infection rate and the hospitalization rate compared with the dose of 300 mg (p = 0.0001, p = 0.007, respectively). As a treatment, Evusheld showed a significant decrease in the mortality rate over the placebo group (p = 0.01) in COVID-19 patients.

Conclusion

This result indicated that Evusheld was an effective prophylactic and therapeutic drug for COVID-19 infection, especially for immunocompromised patients, but there was no considerable variation between the high and low doses. Further prospective and randomized controlled trials (RCTs) with increased population sizes are necessary to show the valuable benefit of the high dose of Evusheld in COVID-19 prevention and treatment and to compare the difference between the two doses within adverse events.
Cognitive behavioural therapy for social anxiety disorder in people with bipolar disorder: a case series
Authors: Pavlova Barbara , Warnock-Parkes Emma , Alda Martin , Uher Rudolf , Clark David M.
Published: January 2024

Background

Social anxiety disorder increases the likelihood of unfavourable outcomes in people with bipolar disorder. Cognitive behavioural therapy (CBT) is the first-line treatment for social anxiety disorder. However, people with bipolar disorder have been excluded from the studies that this recommendation is based on. 

Method

We completed a case series to obtain initial data on whether CBT is an acceptable, safe, and effective treatment for social anxiety disorder in people with bipolar disorder.

Results

Eleven euthymic participants with bipolar disorder attended up to sixteen treatment and three follow-up sessions of CBT for social anxiety disorder. Participants attended on average 95% of the offered CBT sessions. No adverse events were reported. Participants’ mean score on the Social Phobia Inventory decreased from 46.5 (SD 6.6) before the treatment to 19.8 (SD 11.9) at the end of the sixteen-session intervention and further to 15.8 (SD 10.3) by the end of the 3-month follow-up. This degree of improvement is equivalent to the effect observed in studies of CBT for social anxiety disorder in people without severe mental illness.

Conclusions

This case series provides preliminary evidence that CBT is acceptable, safe, and effective for treating social anxiety disorder in people with bipolar disorder during euthymia. A randomized controlled trial is needed to confirm these findings, and to establish whether treatment for social anxiety disorder improves the course of bipolar disorder.
Falling on deaf ears: interpreters as cultural brokers in mental healthcare
Authors: Bamford Jordan , Abraham Seri , Alachkar Mustafa , Akinola Adeola
Published: January 2024

Communication is the cornerstone of mental healthcare. In the UK, many people who will need access to mental health services do not possess English as their first language. In this editorial, we seek to examine current policy and guidance with respect to interpreting in mental healthcare, and explore the benefits and challenges of interpretation and the ethical implications to consider. We focus on how mental health services could better engage with interpreters as cultural brokers to understand cultural expressions of distress. We conclude by suggesting an education and research agenda which could decrease ethnic disparities in mental healthcare.
Gender differences in prevalence and clinical risk factors of suicide attempts in young adults with first-episode drug-naive major depressive disorder
Authors: Zhu Quanfeng , Lang Xiaoe , Zhang Xiang-Yang
Published: January 2024

Background

Suicide rates in adolescents with major depressive disorder (MDD) change with age and gender. Early adulthood is an important transitional stage between late adolescence and adulthood, in which an individual's mind gradually matures. However, there are fewer studies on prevalence and variables linked to the suicide attempts of young adults with MDD.

Aims

To explore gender differences in the prevalence and risk factors associated with suicide attempts in young adults with first-episode drug-naive MDD.

Method

The Hamilton Rating Scale for Depression (HRSD), Hamilton Rating Scale for Anxiety (HRSA) and Positive Subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess depression, anxiety and psychotic symptoms respectively and various biochemical indicators were assessed.

Results

Among 293 young adults with first-episode drug-naive MDD, the prevalence of suicide attempts was 15.45% (19/123) for males and 14.12% (24/170) for females. Males with suicide attempts had higher levels of thyroid-stimulating hormone (TSH) and higher PANSS Positive Subscale scores, whereas females with suicide attempts had higher TSH, serum total cholesterol, fasting blood glucose and diastolic blood pressure levels and higher scores on the HRSD, HRSA, PANSS Positive Subscale (all Bonferroni corrected P < 0.05). In males, PANSS Positive Subscale score (B = 0.17, P = 0.03, OR = 1.19, 95% CI 1.02–1.38) was a risk factor for suicide attempts.

Conclusions

There were significant gender differences in the risk factors for suicide attempts in young adults with first-episode drug-naive MDD.
Cancer Radiomic and Perfusion Imaging Automated Framework: Validation on Musculoskeletal Tumors
Authors: Sierra Elvis Duran , Valenzuela Raul , Canjirathinkal Mathew A. , Costelloe Colleen M. , Moradi Heerod , Madewell John E. , Murphy William A. , Amini Behrang
Published: January 2024

PURPOSE

Limitations from commercial software applications prevent the implementation of a robust and cost-efficient high-throughput cancer imaging radiomic feature extraction and perfusion analysis workflow. This study aimed to develop and validate a cancer research computational solution using open-source software for vendor- and sequence-neutral high-throughput image processing and feature extraction.

METHODS

The Cancer Radiomic and Perfusion Imaging (CARPI) automated framework is a Python-based software application that is vendor- and sequence-neutral. CARPI uses contour files generated using an application of the user's choice and performs automated radiomic feature extraction and perfusion analysis. This workflow solution was validated using two clinical data sets, one consisted of 40 pelvic chondrosarcomas and 42 sacral chordomas with a total of 82 patients, and a second data set consisted of 26 patients with undifferentiated pleomorphic sarcoma (UPS) imaged at multiple points during presurgical treatment.

RESULTS

Three hundred sixteen volumetric contour files were processed using CARPI. The application automatically extracted 107 radiomic features from multiple magnetic resonance imaging sequences and seven semiquantitative perfusion parameters from time-intensity curves. Statistically significant differences ( P < .00047) were found in 18 of 107 radiomic features in chordoma versus chondrosarcoma, including six first-order and 12 high-order features. In UPS postradiation, the apparent diffusion coefficient mean increased 41% in good responders ( P = .0017), while firstorder_10Percentile ( P = .0312) was statistically significant between good and partial/nonresponders.

CONCLUSION

The CARPI processing of two clinical validation data sets confirmed the software application's ability to differentiate between different types of tumors and help predict patient response to treatment on the basis of radiomic features. Benchmark comparison with five similar open-source solutions demonstrated the advantages of CARPI in the automated perfusion feature extraction, relational database generation, and graphic report export features, although lacking a user-friendly graphical user interface and predictive model building.
Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study
Authors: Zingeta Girum Tessema , Worku Yohannes Tesfaye , Awol Munir , Woldetsadik Edom Seife , Assefa Mathewos , Chama Tsion Zebdios , Feyisa Jilcha Diribi , Bedada Hawi Furgassa , Adem Mohammed Ibrahim , Mengesha Tariku , Wong Rebecca
Published: January 2024

PURPOSE

Head and neck cancers (HNCs) are the third most commonly treated cancer with radiation in Ethiopia. Most patients present with advanced stage and are not candidates for curative treatment. The objective of our study is to assess the outcome of hypofractionated palliative radiotherapy (RT) for advanced HNCs in a resource-limited setting.

MATERIALS AND METHODS

Patients with histology-proven advanced HNC candidates for hypofractionated palliative RT were enrolled. Three regimens were allowed: 44.4 Gy in 12 fractions, 30 Gy in 10 fractions, and 20 Gy in five fractions. Response to treatment was assessed at baseline and at 4 weeks after treatment completion. The Kaplan-Meier curve was used to measure the survival.

RESULTS

Between January 2022 and January 2023, 52 patients were enrolled and 25 patients were eligible for outcome assessment. Index symptoms include pain, bleeding, dysphagia, respiratory distress, and others in 25, 13, 10, 6, and 17 patients, respectively. Complete relief of the top three symptoms include pain in 52% of patients, hemostasis in 84% of patients, and dysphagia in 30% of patients. Objectively, 64% of patients attained partial response. For 48% of patients, their quality of life (QoL) improved in one parameter of the physical scores. Moreover, 64% of patients showed improvement in three parameters. The global functional score improved in 80% of patients. One patient had grade 3 xerostomia. At the end of the study period, 44% of patients died. The median survival after radiation was 9 months (95% CI, 7.2 to 10.8)

CONCLUSION

All palliative hypofractionated regimens used were effective in terms of symptom control, tumor response rate, and QoL, and were well tolerated. This makes it appropriate for our setup because the majority of patients require palliation.
Effectiveness of Immune Checkpoint Inhibitors in Various Tumor Types Treated by Low, Per-Weight, and Conventional Doses at a Tertiary Care Center in Mumbai
Authors: Patel Amol , Hande Vivek , MR Kaushik , Dange Hemendra , Das Amit Kumar , Murugesan Vigneshwaran , Bhatt Trilok , Shankaran Ramakrishnan
Published: January 2024

PURPOSE

The cost of immune checkpoint inhibitors (ICIs) limits their accessibility to a small number of patients with cancer in low- and middle-income countries. Early-phase clinical trials have shown target inhibition and high activity at doses lower than those registered and evaluated in clinical trials. Here, we report everyday experience of using ICIs in 100 Indian patients, many of whom received lower doses of ICIs.

METHODS

Consecutive patients who received at least one dose of an ICI irrespective of tumor type at a tertiary care hospital in Mumbai, India, that was able to access ICIs for its patients were enrolled. The objectives were to study the doses used over a 3-year time period, and the effectiveness of therapy, assessed primarily by the overall response rate (ORR), overall survival (OS), and progression-free survival were secondary end points.

RESULTS

Twenty-five patients were treated with conventional doses of ICIs, 29 patients received lower doses per body weight, and 46 patients received low-dose treatment. The median number of cycles received was 5 (range, 1-28). Seventy-eight patients received ICIs in a palliative setting. The median follow-up time was 10.2, 9.8, and 3.9 months for those receiving fixed approved dosing, per body weight dosing, and low-dose treatment, respectively. There was a trend with time to prescribe lower doses. Response evaluation was available for 92 patients. Twenty-one (five-adjuvant and 16-palliative) patients received ICIs only. The ORR did not differ statistically among different dosing groups, but comparisons are confounded by inclusion of different ICIs, different tumor sites, and concurrent treatments. The median OS was 6.8 (range, 4.6-9.0) months.

CONCLUSION

Adoption of per-body weight and lower dosing of ICIs appears to give acceptable outcomes. Lower dosing can improve access and timely delivery of ICIs in low- and middle-income countries.
Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study
Authors: Pinto Carmine , Orlandi Armando , Normanno Nicola , Maiello Evaristo , Calegari Maria A. , Antonuzzo Lorenzo , Bordonaro Roberto , Zampino Maria G. , Pini Sara , Bergamo Francesca , Tonini Giuseppe , Avallone Antonio , Latiano Tiziana P. , Rosati Gerardo , Cogoni Alessio Aligi , Ballestrero Alberto , Zaniboni Alberto , Roselli Mario , Tamberi Stefano , Barone Carlo
Published: January 2024

PURPOSE

The intensity of anti-EGFR–based first-line therapy for RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC), once disease control is achieved, is controversial. A de-escalation strategy with anti-EGFR monotherapy represents a potential option to maintain efficacy while reducing cytotoxicity.

METHODS

In this multicenter, open-label, phase III trial, patients with untreated RAS/BRAF wt mCRC were randomly assigned to receive either fluorouracil, leucovorin, and irinotecan/cetuximab (FOLFIRI/Cet) until disease progression (arm A) or FOLFIRI/Cet for eight cycles followed by Cet alone (arm B). The coprimary end points were a noninferior progression-free survival (PFS) in the modified per-protocol (mPP) population (>eight cycles) and a lower incidence of grade (G) 3-4 adverse events (AEs) for arm B compared with arm A.

RESULTS

Overall, 606 patients were randomly assigned, with 300 assigned to arm A and 306 to arm B. The median follow-up was 22.3 months. In the mPP population, 291 events occurred with a PFS of 10 versus 12.2 months for arms B and A, respectively ( P of noninferiority = .43). In the intention-to-treatment (ITT, ≥one cycle) population, 503 events occurred with a PFS of 9 versus 10.7 months ( P = .39). The overall survival was 35.7 versus 30.7 months ( P = .119) and 31.0 versus 25.2 months ( P = .32) in the mPP and ITT population, respectively. Arm B had lower G3-4 AEs during the maintenance period than arm A (20.2% v 35.1%).

CONCLUSION

The ERMES study did not demonstrate noninferiority of maintenance with Cet alone. Despite a more favorable safety profile, maintenance with single-agent Cet after induction with FOLFIRI/Cet cannot be recommended for all patients but could represent an option in selected cases.
Cancer-Associated Thrombosis: Management of a Patient With an Isolated Calf Deep Vein Thrombosis
Authors: Soff Gerald A.
Published: January 2024

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

Venous thromboembolism occurs frequently in patients with cancer and is the second leading cause of death, after the cancer itself. There is a well-established consensus of the need for anticoagulation in patients with a proximal deep vein thrombosis or pulmonary embolism. But with improved imaging technology and widescale use of contrast imaging for cancer staging, many incidental pulmonary emboli are detected in patients with cancer. Furthermore, many isolated distal deep vein thromboses and subsegmental pulmonary emboli are identified. There have been questions if these small or asymptomatic thromboses require anticoagulation management similar to more proximal or symptomatic thromboses. In this Oncology Grand Rounds, we will review the existing evidence for these situations. We will also review management strategies for cancer-associated thrombosis, reflecting the evolving drugs and evidence over the past 20 years.
Update on Adrenarche—Still a Mystery
Authors: Augsburger Philipp , Liimatta Jani , Flück Christa E
Published: January 2024

Context

Adrenarche marks the timepoint of human adrenal development when the cortex starts secreting androgens in increasing amounts, in healthy children at age 8–9 years, with premature adrenarche (PA) earlier. Because the molecular regulation and significance of adrenarche are unknown, this prepubertal event is characterized descriptively, and PA is a diagnosis by exclusion with unclear long-term consequences.

Evidence Acquisition

We searched the literature of the past 5 years, including original articles, reviews, and meta-analyses from PubMed, ScienceDirect, Web of Science, Embase, and Scopus, using search terms adrenarche, pubarche, DHEAS, steroidogenesis, adrenal, and zona reticularis.

Evidence Synthesis

Numerous studies addressed different topics of adrenarche and PA. Although basic studies on human adrenal development, zonation, and zona reticularis function enhanced our knowledge, the exact mechanism leading to adrenarche remains unsolved. Many regulators seem involved. A promising marker of adrenarche (11-ketotestosterone) was found in the 11-oxy androgen pathway. By current definition, the prevalence of PA can be as high as 9% to 23% in girls and 2% to 10% in boys, but only a subset of these children might face related adverse health outcomes.

Conclusion

New criteria for defining adrenarche and PA are needed to identify children at risk for later disease and to spare children with a normal variation. Further research is therefore required to understand adrenarche. Prospective, long-term studies should characterize prenatal or early postnatal developmental pathways that modulate trajectories of birth size, early postnatal growth, childhood overweight/obesity, adrenarche and puberty onset, and lead to abnormal sexual maturation, fertility, and other adverse outcomes.
Approach to the Peripubertal Patient With Short Stature
Authors: Torres-Santiago Lournaris , Mauras Nelly
Published: January 2024

Context

The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding number of conditions impeding growth are being identified. Among endocrine-related etiologies of short stature amenable to hormonal treatment, defects in the growth hormone (GH)–insulin-like growth factor I axis remain pre-eminent, with a multiplicity of disorders causing decreased secretion or insensitivity to GH action. Sex steroids in puberty increase epiphyseal senescence and eventual growth plate closure. This is mediated mostly via estrogen receptor (ER)α in males and females, effects that can greatly limit time available for growth.

Evidence Acquisition

Extensive literature review through PubMed and other search engines.

Evidence Synthesis

Therapeutic strategies to be considered in peripubertal and pubertal children with disordered growth are here discussed, including daily and weekly GH, low-dose sex steroids, gonadotropin hormone releasing hormone (GnRH) analogues in combination with GH, aromatase inhibitors (AIs) alone and in combination with GH in boys. When used for at least 2 to 3 years, GnRH analogues combined with GH can result in meaningful increases in height. AIs used with GH permit puberty to progress in boys without hindrance, selectively decreasing estrogen, and resulting in taller height. With more than 20 years of cumulative experience in clinical use of these medications, we discuss the safety profile of these treatments.

Conclusion

The approach of growth retardation in the peripubertal and pubertal years must consider the sex steroid milieu and the tempo of bone acceleration. Treatment of affected children in this period must be individualized.
Efficacy and Safety of Denosumab vs Zoledronic Acid in OI Adults: A Prospective, Open-Label, Randomized Study
Authors: Lin Xiaoyun , Hu Jing , Zhou Bingna , Wang Xiaojie , Zhang Qian , Jiang Yan , Wang Ou , Xia Weibo , Xing Xiaoping , Li Mei
Published: January 2024

Context

The comparative effectiveness of denosumab and zoledronic acid for adult patients with osteogenesis imperfecta (OI) has not been established.

Objective

To evaluate the efficacy and safety of denosumab and zoledronic acid in adult patients with OI.

Methods

This was a prospective, open-label study. Patients were randomized to receive denosumab 60 mg every 6 months or zoledronic acid 5 mg once for 12 months. Pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Percentage changes in the areal bone mineral density (aBMD), trabecular bone score (TBS), and bone turnover biomarkers (BTMs) from baseline to 6 and 12 months of treatment, as well as safety, were evaluated.

Results

A total of 51 adults with OI (denosumab: 25, zoledronic acid: 26) were included, of whom 49 patients had identified pathogenic mutations. At 12 months, aBMD at the lumbar spine and total hip significantly increased by 4.34% (P = .005) and 1.45% (P = .023) in the denosumab group and by 4.92% (P = .006) and 2.02% (P = .016) in the zoledronic acid group, respectively. TBS showed an increasing trend by 1.39% and 2.70% in denosumab and zoledronic acid groups, respectively. Serum levels of β-isomerized carboxy-telopeptide of type I collagen and alkaline phosphatase markedly decreased after denosumab treatment. Percentage changes in aBMD, TBS, and BTMs during the treatment were similar between the 2 groups. Patients with OI with milder phenotypes showed a significantly higher increase in the TBS after 12 months of denosumab treatment than those with more severe phenotypes (P = .030). During the study period, the denosumab group had fewer adverse events than the zoledronic acid group.

Conclusion

Denosumab effectively increases aBMD in adults with OI, with similar efficacy to zoledronic acid. Long-term and large-sample studies are needed to confirm the antifracture efficacy and safety of denosumab in adult patients with OI.
Granulosa Cells Alone, Without Theca Cells, Can Mediate LH-induced Oocyte Meiotic Resumption
Authors: Norris Rachael P , Jaffe Laurinda A
Published: January 2024

Signaling in the granulosa cells of mammalian ovarian follicles is necessary for maintaining prophase arrest in the oocyte and for mediating the resumption of meiosis in response to luteinizing hormone (LH). However, the follicle also includes an outer layer of theca cells, some of which express receptors for LH. To investigate whether theca cells are required for maintaining meiotic arrest and reinitiating meiosis in response to LH, we mechanically separated the granulosa cells and oocyte from the theca and basal lamina. This was accomplished by cutting a slit in the outer surface of isolated follicles such that the mural granulosa cells and cumulus-oocyte complex were extruded from the theca shell, forming a lawn of cells on an organotypic membrane. The remnant of theca cells and basal lamina was then removed. The separation of the granulosa cells from the theca cells and basal lamina was demonstrated by immunofluorescence localization of endomucin (blood vessels of the theca) and laminin gamma (basal lamina). Cells comprising these granulosa cell-oocyte complexes expressed LH receptors and were connected by gap junctions. Oocytes within these granulosa cell complexes maintained meiotic arrest and resumed meiosis in response to LH, showing that the granulosa cells alone, without theca cells, transduce these signals. This semi-intact and mostly 2-dimensional preparation could facilitate imaging studies of follicle physiology.
Face-valid phenotypes in a mouse model of the most common mutation in EEF1A2-related neurodevelopmental disorder
Authors: Marshall Grant F. , Fasol Melissa , Davies Faith C. J. , Le Seelleur Matthew , Fernandez Alvarez Alejandra , Bennett-Ness Cavan , Gonzalez-Sulser Alfredo , Abbott Catherine M.
Published: January 2024

De novo heterozygous missense mutations in EEF1A2, encoding neuromuscular translation-elongation factor eEF1A2, are associated with developmental and epileptic encephalopathies. We used CRISPR/Cas9 to recapitulate the most common mutation, E122K, in mice. Although E122K heterozygotes were not observed to have convulsive seizures, they exhibited frequent electrographic seizures and EEG abnormalities, transient early motor deficits and growth defects. Both E122K homozygotes and Eef1a2-null mice developed progressive motor abnormalities, with E122K homozygotes reaching humane endpoints by P31. The null phenotype is driven by progressive spinal neurodegeneration; however, no signs of neurodegeneration were observed in E122K homozygotes. The E122K protein was relatively stable in neurons yet highly unstable in skeletal myocytes, suggesting that the E122K/E122K phenotype is instead driven by loss of function in muscle. Nevertheless, motor abnormalities emerged far earlier in E122K homozygotes than in nulls, suggesting a toxic gain of function and/or a possible dominant-negative effect. This mouse model represents the first animal model of an EEF1A2 missense mutation with face-valid phenotypes and has provided mechanistic insights needed to inform rational treatment design.
RhoU forms homo-oligomers to regulate cellular responses
Authors: Clayton Natasha S. , Hodge Richard G. , Infante Elvira , Alibhai Dominic , Zhou Felix , Ridley Anne J.
Published: January 2024

RhoU is an atypical member of the Rho family of small G-proteins, which has N- and C-terminal extensions compared to the classic Rho GTPases RhoA, Rac1 and Cdc42, and associates with membranes through C-terminal palmitoylation rather than prenylation. RhoU mRNA expression is upregulated in prostate cancer and is considered a marker for disease progression. Here, we show that RhoU overexpression in prostate cancer cells increases cell migration and invasion. To identify RhoU targets that contribute to its function, we found that RhoU homodimerizes in cells. We map the region involved in this interaction to the C-terminal extension and show that C-terminal palmitoylation is required for self-association. Expression of the isolated C-terminal extension reduces RhoU-induced activation of p21-activated kinases (PAKs), which are known downstream targets for RhoU, and induces cell morphological changes consistent with inhibiting RhoU function. Our results show for the first time that the activity of a Rho family member is stimulated by self-association, and this is important for its activity.
A Ramp versus Step Transition to Constant Work Rate Exercise Decreases Steady-State Oxygen Uptake
Authors: MARINARI GABRIELE , IANNETTA DANILO , HOLASH ROBERT JOHN , TRAMA ROBIN , FARICIER ROBIN , ZAGATTO ALESSANDRO M. , KEIR DANIEL A. , MURIAS JUAN M.
Published: January 2024

Within the initial minutes of square-wave exercise transitions above the moderate-intensity domain, the reliance on the anaerobic energy sources may induce some levels of metabolic instability; however, no study has attempted to limit metabolic instability at exercise onset by manipulating the exercise transition phase to a target work rate (WR).

Purpose

This study aimed to investigate whether a ramp-to-constant WR (rCWR) transition compared with a square-wave-to-constant WR (CWR) transition within the heavy-intensity domain can reduce metabolic instability and decrease the oxygen cost of exercise.

Methods

Fourteen individuals performed (i) a ramp-incremental test to task failure, (ii) a 21-min CWR within the heavy-intensity domain, and (iii) an rCWR to the same WR. Oxygen uptake (V̇O2), lactate concentration ([La−]), and muscle oxygen saturation (SmO2) were measured. V̇O2 and V̇O2 gain (V̇O2-G) during the first 10-min steady-state V̇O2 were analyzed. [La−] before, at, and after steady-state V̇O2 and SmO2 during the entire 21-min steady-state exercise were also examined.

Results

V̇O2 and V̇O2-G during rCWR (2.49 ± 0.58 L·min−1 and 10.7 ± 0.2 mL·min−1·W−1, respectively) were lower (P < 0.001) than CWR (2.57 ± 0.60 L·min−1 and 11.3 ± 0.2 mL·min−1·W−1, respectively). [La−] before and at steady-state V̇O2 during the rCWR condition (1.94 ± 0.60 and 3.52 ± 1.19 mM, respectively) was lower than the CWR condition (3.05 ± 0.82 and 4.15 ± 1.25 mM, respectively) (P < 0.001). [La−] dynamics after steady-state V̇O2 were unstable for the rCWR (P = 0.011). SmO2 was unstable within the CWR condition from minutes 4 to 13 (P < 0.05).

Conclusions

The metabolic disruption caused by the initial minutes of square-wave exercise transitions is a primary contributor to metabolic instability, leading to an increased V̇O2-G compared with the rCWR condition approach. The reduced early reliance on anaerobic energy sources during the rCWR condition may be responsible for the lower V̇O2-G.
Reducing discrimination against service users with psychosis through brief contact-based video interventions: a randomised controlled trial
Authors: Mankiewicz Pawel D , Tan Audrina SY
Published: January 2024

Background/Aims

Internationally, mental health service users, particularly those with psychosis, face discriminatory attitudes and behaviours from the public. It is crucial for mental health services to deliver interventions that alleviate the stigma directed toward their patients. This study evaluates the efficacy of a brief indirect contact-based intervention designed for this purpose in Singapore.

Methods

A randomised controlled trial was conducted among 168 participants, who were allocated to video intervention, transcript intervention and active control groups. Stigmatising behaviour levels were measured at pre-intervention, post-intervention and at a 30-day follow up. Group differences in attitudes were analysed using a 3x3 two-way mixed subjects ANOVA, with significance set at P<0.05.

Results

There were no significant differences in declared discriminatory behaviour between the investigated conditions (P=0.23). The video intervention did not produce superior results to the transcript, while the results of both interventions did not differ significantly from those of the control condition. Additionally, no significant interaction of each condition with time was observed at the post-intervention and follow-up periods (P=0.5).

Conclusions

Individual contact-based interventions may not sustainably reduce discrimination towards mental health service users. Services should prioritise strategies to specifically target the societal mechanisms that maintain stigmatising behaviour towards people with psychosis.
Phytochemical Composition, Antimycotic and In Vivo Antiinflammatory Activities of Marine Algae Inhabiting South Jeddah Seashore, Red Sea, Saudi Arabia
Authors: Abusuliman Aghaida M. , Amin Abeer S. , Higo Mona A. , Saddiq Amna A. , Tag Hend M.
Published: January 2024

The Red Sea coastline is known for its diverse range of seaweeds, which have been hypothesized to possess therapeutic attributes. The primary aim of this research was to evaluate the antifungal and anti-inflammatory characteristics of the ethanol crude extract obtained from two types of algae, namely Padina pavonica (P. pavonica) and Laurencia catarinensis (L. catarinensis) from the Red Sea. It was revealed from FTIR analysis of P. pavonica and L. catarinensis ethanolic extracts that the strong band at 3366 cm−1 and 3339 cm−1 corresponds to alcoholic O-H stretching in both extracts. GC-MS phytoconstituent profile of the extract was dominant with a wide range of chemical classes mainly steroids, terpenes, fatty acids, fatty acid esters, retinoid derivatives, alcohols, carotenoids and alkanes. The results of the antifungal activity assay indicate that P. pavonica had the strongest activity against Aspergillus fumigatus, with a mean value of 23.50 ± 0.55 mm. Similarly, L. catarinensis demonstrated significant antifungal activity against Candida albicans, with a mean value of 21.00 ± 2.64 mm. The hemolysis exhibited a positive correlation with the dosage of extracts, with an observed increase in hemolysis as the dosage increased. Besides the antiinflammatory activity of the algal extracts induced by carrageenan demonstrating a dose-dependent relationship between the inhibition of paw edema and the dosage of the extract.
Slow-Chronic Progressive Hydrocephalus as Complication of Microvascular Decompression for Trigeminal Neuralgia: A Case Report
Authors: Niryana* I Wayan , Awyono Steven , Ranuwibawa Made Satriya , Lauren Christopher
Published: January 2024

Microvascular decompression (MVD) is one of the well-established treatment options for trigeminal neuralgia that may include posterior fossa surgery. However, Several complications were noted as being part of posterior fossa surgery and hydrocephalus is very rare to occur, especially the slow-chronic onset type. The pathophysiology is still unclear, but surgeons and patients must be warned about this possible surgical adverse event. Here we report a case of slow-chronic hydrocephalus in a 66-years old male who has a history of MVD procedure due to left trigeminal neuralgia. A shunt procedure was performed, in which after the surgery the patient’s complaints were resolved, and discharged without any morbidity.
The Effect of Hydrothermal Reaction Time on the Antibacterial Activity of Synthesized Manganese Oxide Nanoparticles
Authors: R. Vaideeswaran  , A. Yuvarani  , I. Sophia Rani  , I. Reeta Mary
Published: January 2024

In the context of growing antibiotic resistance and the associated side effects of traditional antibiotics, this research explores the use of nanosized manganese oxide (Mn3O4) as a novel antibacterial agent. This study pioneers the synthesis of Mn3O4 through an eco-friendly hydrothermal method, varying reaction times (2, 4 and 6 hours) at a consistent temperature of 180 °C. Characterization techniques, including X-ray diffraction, Fourier-transform infrared spectroscopy and Scanning electron microscopy, provide insights into their crystallinity, functional groups and morphology. The synthesized Mn3O4 demonstrates remarkable antibacterial efficacy, with larger inhibition zones against both Gram-positive and Gram-negative strains compared to standard antibiotics. This research presents the synthesizing of an eco-friendly, cost-effective antibacterial agent through a straightforward hydrothermal method. Varying reaction times unveil distinctive antibacterial capabilities, making Mn3O4 a promising candidate for future antimicrobial systems and medical applications.
Analysing expert advice on political decisions in times of crisis
Authors: Aagaard Peter , Chatzopoulou Sevasti , Poulsen Birgitte
Published: January 2024

This article analyses the relationship between expert knowledge and political decision-making during the COVID-19 pandemic in Denmark, Greece and the United States. Due to the swift spread of the COVID-19 virus across the globe, the management of the pandemic required urgent government responses. Our empirical findings enabled us to identify a new typology of different types of advice, from naked power to technocracy, including in-between modes of networking and interactions. We also demonstrate how systemic and governance characteristics affect expert-politics responses in the three countries. The findings demonstrate similar responses in Greece and Denmark, by contrast with the United States. We conclude by proposing a new research agenda for expert-politician relations during crises, which focuses on the role of experts in public sensemaking, which is particularly important in an era of recurring and overlapping crises.
Identifying proactive and reactive policy entrepreneurs in collaborative networks in flood risk management
Authors: Becker Per , Sparf Jörgen , Petridou Evangelia
Published: January 2024

A policy entrepreneur is a distinct political actor aiming to affect change. The theoretical narrative regarding policy entrepreneurs is underpinned by their commitment to a policy solution, the multi-dimensional strategies they use to promote that solution, and a suite of attributes and skills facilitating their actions. Policy entrepreneurs reveal themselves through their attempts to transform policy ideas into policy innovations and, hence, disrupt status quo policy arrangements. Indeed, policy entrepreneurs share sensibilities with entrepreneurs in the market, whose conceptualisation serves as a heuristic for their counterparts in policy and politics. The emphasis on change borne out of innovative solutions distinguishes policy entrepreneurs from many other actors who aim to maintain current institutional settings and power relations. The growing scholarship on policy entrepreneurship assumes intentionality as inherent to the policy entrepreneur and their actions, foregrounding the image of the tenacious political actor set on steering their a priori pet policy to a suitable problem. This article draws from the market theory on entrepreneurship, contrasting proactive policy entrepreneurship (entrepreneurship by opportunity) and reactive policy entrepreneurship (entrepreneurship by necessity). We conduct a comparative social network analysis of three municipalities in southern Sweden focused on flood risk mitigation. We demonstrate two different logics of policy entrepreneurship (as a result of seizing opportunities versus as a reaction to vertical pressure), and we explore the consequences for enhancing our understanding of policy entrepreneurship.
Difficult Women and Dangerous Memories: Silenced, Suppressed, and Misrepresented Founders in the History of American Religious Life
Authors: Thompson Margaret Susan
Published: January 2024

Abstract: In this essay, I focus on examples of controversial early members of communities of women religious in the United States, particularly their founders, whose significance (and, in some case, even existence) was deliberately obscured or removed from “approved” or “authorized” congregational histories. There are numerous such examples; here, I focus on four (though others figure briefly): Theresa Maxis Duchemin (Sisters, Servants of the Immaculate Heart of Mary), St. Andrew Feltin (Sisters of Divine Providence), Margaret Anna Cusack (Sisters of St. Joseph of Peace), and Wilhelmina Bleily (Sisters of St. Mary of Oregon). In recounting and analyzing their stories, I hope to explain why so many founders (or, at least, their significance) were silenced or repudiated, even by sisters themselves, and what their “rediscovery” in the past half century or so tells us about religious renewal in the post-Vatican II era. To what extent do their experiences derive from particularized circumstances and contextual factors? To what extent do their stories collectively inform us about important kyriarchal conditions during this formative period in apostolic women’s religious life? Moreover, despite often aggressive efforts to erase their stories or to deny their contributions, why was their influence never completely eradicated? What does this tell us about “official” and “unofficial” history, particularly for what it reveals about women’s responses to patriarchy? These accounts challenge us to see beyond a prescriptive or hagiographic understanding of women’s religious life and to appreciate the complexity of its reality.
Professional Learning in Student Affairs Graduate Preparation
Authors: Hunter Graham F.
Published: January 2024

Abstract: This study explores how students’ professional learning is distributed across and mediated by multiple learning environments during student affairs graduate preparation. Utilizing activity system analysis and qualitative case study, the study reports on the experiences of four second-year Master’s students at a Midwest preparation program. Findings demonstrate how fieldwork experiences shape what graduate students deem as essential or useful knowledge for their practice and, consequently, the value they place on coursework experiences. Participants often rejected formal knowledge when it did not offer clear and immediate solutions to their daily problems. This study raises implications for individuals working with graduate students regarding their professional development, especially faculty members and fieldwork supervisors.
“An Empty Promise”: Experiences of Student Affairs Professionals of Color
Authors: Hutchings Quortne R , Franco Carerra Lillianna , Noriega Cristian
Published: January 2024

Abstract: Student Affairs Professionals of Color (SAPC) serve a critical role in the field of higher education. Using a phenomenological approach, this study gathered data from semi-structured interviews with eight SAPC from various backgrounds and institutions. Findings from this study illuminated how the participating SAPC experienced code-switching, student affairs fatigue, and professional crossroads. This study revealed a trend in which SAPC felt a lack of fulfillment and encountered unmet expectations in the profession. This research offers key recommendations for future exploration and practice to improve the field of student affairs and higher education for SAPC.
Challenge or Support? Exploring Academic Burnout in Residential Learning Communities
Authors: Stoner James C. , Erck Ryan W. , Sriram Rishi , Peña Madeline
Published: January 2024

Abstract: Residential learning communities (RLCs) are on-campus programs aimed at seamlessly blending the in- and out-of-class experiences for college students. Scholars have demonstrated how RLC initiatives are valuable because they build and reinforce an academic environment, and help facilitate related outcomes (e.g., academic transition, GPA, critical thinking). With such an emphasis on aligning academic and residential experiences for students, this article explored if RLC participants were susceptible to higher rates of academic burnout. Using survey data to assess RLC and non-RLC students, we established that participation was not associated with meaningful differences in academic burnout. Conversely, by measuring thriving we also determined that the ways students experience success in RLCs is in fact different than their non-RLC counterparts. Student affairs practitioners can better understand how their students experience burnout when they also understand how their students succeed, as demonstrated in the study’s findings. Recommendations to alleviate burnout while promoting success are discussed in light of RLC participation.