bluuebunny/crossref_metadata_2025 huggingface dataset:
Real influence: A novel approach to characterize the visibility of journals and publications
Authors: Perianes-Rodríguez Antonio , Mira Bianca S. , Martínez-Ávila Daniel , Grácio Maria Cláudia Cabrini
Published: July 2024

For the last 50 years, the journal impact factor (IF) has been the most prominent of all bibliometric indicators. Since the first Journal Citation Report was launched, the IF has been used, often improperly, to evaluate institutions, publications, and individuals. Its well-known significant technical limitations have not detracted from its popularity, and they contrast with the lack of consensus over the numerous alternatives suggested as complements or replacements. This paper presents a percentile-distribution-based proposal for assessing the influence of scientific journals and publications that corrects several of the IF’s main technical limitations using the same set of documents as is used to calculate the IF. Nearly 400 journals of Library Science and Information Science and Biochemistry and Molecular Biology categories were analyzed for this purpose. The results show that the new indicator retains many of its predecessor’s advantages and adds benefits of its own: It is more accurate, more gaming resistant, more complete, and less influenced by the citation window or extreme observations.
Coccinellidae (Coleoptera: Coccinelloidea) from Colombia: A systematic and illustrated list
Authors: GONZÁLEZ GUILLERMO , KONDO TAKUMASA , GASCA-ÁLVAREZ HÉCTOR JAIME , SANDOVAL-ESPINEL MADELYN KATHERINE , NIÑO-SUÁREZ MAYRA ALEJANDRA , MORENO MAIRA ALEJANDRA ZAMBRANO
Published: July 2024

A synopsis of the family Coccinellidae of Colombia is presented, including an annotated list of the species recorded in the country based on published data, a revision of national and foreign collections, and information obtained from citizen science. The list includes 404 species grouped in 81 genera, 21 tribes and two subfamilies. There are 395 native species recorded (among them 201 considered endemic), and nine introduced. For each species, taxonomic information, background on its biology, its usage in biological control and geographic distribution are included. Images of their habitus, living specimens and distribution maps for Colombia and the Americas are also included. Twenty species were recorded for the first time for Colombia, nine for Ecuador, five for Peru and Venezuela, three for French Guiana, two for Brazil and one for Argentina, Cuba, Paraguay, and Puerto Rico, respectively. The coccinellid fauna of Colombia is compared with other countries in South America in terms of the diversity, endemism, and geographical distribution. Two nomenclatural changes are proposed because of homonymy: Hyperaspis amati González is a new name for Hyperaspis mimica Gordon & González, 2011, and Hyperaspis octomaculata González is a new name for Hyperaspis octonotata Gordon & Canepari, 2008.
Transient Tropopause Waves
Authors: Dörnbrack Andreas
Published: July 2024

Flight-level airborne observations have often detected gravity waves with horizontal wavelengths near the tropopause. Here, in situ and remote sensing aircraft data of these short gravity waves trapped along tropopause inversion layer and collected during a mountain-wave event over southern Scandinavia are analyzed to quantify their spectral energy and energy fluxes and to identify nonstationary modes. A series of three-dimensional numerical simulations are performed to explain the origin of these transient wave modes and to investigate the parameters on which they depend. It turns out that mountain-wave breaking in the middle atmosphere and the subsequent modification of the stratospheric flow are the key factors for the occurrence of trapped modes with . In particular, the intermittent and periodic breaking of mountain waves in the lower stratosphere forms a wave duct directly above the tropopause, in which the short gravity waves are trapped. The characteristics of the trapped, downstream-propagating waves are mainly controlled by the sharpness of the tropopause inversion layer. It could be demonstrated that different settings for optimizing the numerical solver have a significantly smaller influence on the solutions.
Representation of Blowing Snow and Associated Visibility Reduction in an Operational High-Resolution Weather Model
Authors: Corrie Timothy D. , Geerts Bart , Smirnova Tatiana G. , Benjamin Stanley G. , Charnick Michael , Brothers Matthew , He Siwei , Lebo Zachary J. , James Eric P.
Published: July 2024

Blowing snow is a hazard for motorists because it may rapidly reduce visibility. Numerical weather prediction models in the United States do not capture the movement of snow once it reaches the ground, but visibility reductions due to blowing snow can be diagnosed based on model-predicted land surface and environmental conditions that correlate with blowing snow occurrence. A recently developed diagnostic framework for forecasting blowing snow concentration and the associated visibility reduction is applied to High-Resolution Rapid Refresh (HRRR) and Rapid Refresh Forecast System (RRFS) model output including surface snow conditions to predict surface visibility reduction due to blowing snow. Twelve blowing snow events around Wyoming from 2018 to 2023 are examined. The analysis shows that visibility reductions due to blowing snow tend to be overpredicted, caused by the initial assumption of full driftability of the snowpack. This study refines the aging of the blowing snow reservoir with two methods. The first method estimates driftability based on time-varying snow density from the Rapid Update Cycle land surface model (RUC LSM) used in the HRRR and experimental RRFS models and is evaluated in a real-time context with the RRFS model. The second, complementary method diagnoses snowpack driftability using a process-based approach that requires data for recent snowfall, wind speed, and skin temperature. Compared to the full driftability assumption, this method shows limited improvements in forecasting skill. To improve model-based diagnosis of visibility reduction due to blowing snow, empirical work is needed to determine the relation between snowpack driftability and the recent history of snowfall and other weather conditions.

Significance Statement

Blowing snow presents a significant hazard to motorists and airport operations through sometimes very rapid and intense reductions in visibility, yet little predictive guidance exists for blowing snow. This study aims to improve the prediction of blowing snow occurrence and associated surface visibility reduction using diagnostics from an operational high-resolution weather model. One key challenge regards the question of driftability of the snowpack. This study evaluates two approaches to quantify driftability in terms of visibility reduction due to blowing snow and acknowledges that more measurements are needed to improve the representation of blowing snow physics in NWP models.
Vitamin B12 Deficiency-Induced Neuropathy and Cognitive and Motor Impairment in the Elderly: A Case Study
Authors: Dekker Marieke J. H. J. , Heerdink Gonneke C. , Plattel Clara H. M.
Published: July 2024

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history.
Vitamin B12-Related Biomarkers
Authors: Nexo Ebba , Parkner Tina
Published: July 2024

Background:

Adult vitamin B12 (B12) deficiency may present itself with nonspecific mainly neurological symptoms, and thus plasma biomarkers are often judged to be of major importance in the further diagnostic process. Four biomarkers are of special relevance: total B12, holotranscobalamin (the part of B12 bound to the active transport protein, transcobalamin, also named holoTC or active B12) and the 2 so-called metabolic markers that accumulate if B12 is lacking, methylmalonic acid (MMA) and homocysteine.

Objective:

This article briefly reviews the inherent limitation of biomarkers, discusses its use in establishing the diagnosis and cause of B12 deficiency, and when following or discontinuing treatment with B12.

Methods:

The review is based on published papers, but also on knowledge gained from working within the area.

Conclusion:

It is concluded that a combination of a B12 and a metabolic marker, for example, total B12 and MMA, may prove most useful in daily practice. An unexpectedly high level of total B12 is most often of no clinical importance, though sometimes related to the presence of underlying cancer. Measurement of total B12 is of limited value in patients on treatment with pharmacological doses of B12 but may be helpful if B12 treatment is discontinued.
A Brief Overview of the Diagnosis and Treatment of Cobalamin (B12) Deficiency
Authors: Wolffenbuttel Bruce H. R. , McCaddon Andrew , Ahmadi Kourosh R. , Green Ralph
Published: July 2024

Background:

An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption.

Objective:

This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency.

Methods:

A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency.

Results:

Prevention and early treatment of B12 deficiency is essential to avoid irreversible neurological consequences. Diagnosis is often difficult due to diverse symptoms, marked differences in diagnostic assays' performance and the unreliability of second-line biomarkers, including holo-transcobalamin, methylmalonic acid and total homocysteine. Reduced dietary intake of B12 requires oral supplementation. In B12 malabsorption, oral supplementation is likely insufficient, and parenteral (i.e. intramuscular) supplementation is preferred. There is no consensus on the optimal long-term management of B12 deficiency with intramuscular therapy. According to the British National Formulary guidelines, many individuals with B12 deficiency due to malabsorption can be managed with 1000 µg intramuscular hydroxocobalamin once every two months after the initial loading. Long-term B12 supplementation is effective and safe, but responses to treatment may vary considerably. Clinical and patient experience strongly suggests that up to 50% of individuals require individualized injection regimens with more frequent administration, ranging from daily or twice weekly to every 2-4 weeks, to remain symptom-free and maintain a normal quality of life. ‘Titration’ of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced. There is currently no evidence to support that oral/sublingual supplementation can safely and effectively replace injections.

Conclusions:

This study highlights the interindividual differences in symptomatology and treatment of people with B12 deficiency. Treatment follows an individualized approach, based on the cause of the deficiency, and tailored to help someone to become and remain symptom-free.
Causes and Risk Factors of Vitamin B12 Deficiency at the Bookends of Life, From Infancy to Old Age
Authors: Green Ralph
Published: July 2024

The causes and risk factors of vitamin B12 deficiency are many and varied. Importantly, they vary considerably across the lifespan, from infancy to old age. The complexity of the physiology of vitamin B12 bespeaks the myriad of possible causes of deficiency and possible disruptions of its functional integrity. These lead ultimately to the pathobiological effects witnessed in deficiency of this fascinating micronutrient. This brief overview of the multiplicity of mechanisms that can result in vitamin B12 deficiency, and the panoply of its manifestations explores the underlying reasons for the protean presentations of the disease. As the human organism progresses through the chronology and milestones of age, various susceptibility factors arise resulting from the interplay of environmental and genetic factors. Acting independently and in concert, these factors produce the common denominator of vitamin B12 deficiency. However, the rate at which such deficiency develops and the way in which it presents clinically vary widely, subject to such influences as genetic variability, end-organ susceptibility, and concomitant micronutrient status. Some examples of unusual cases of vitamin B12 deficiency are described. Much has been learned about the last of the numbered vitamins in almost a century. Much yet remains to be discovered.
Roctavian gene therapy for hemophilia A
Authors: Samelson-Jones Benjamin J. , Small Juliana C. , George Lindsey A.
Published: July 2024

After successful efforts in adeno-associated virus (AAV) gene addition for hemophilia B gene therapy, the development of valoctocogene roxaparvovec (Roctavian; Biomarin) over the past decade represents a potential new hemophilia A (HA) treatment paradigm. Roctavian is the first licensed HA gene therapy that was conditionally approved in Europe in August 2022 and approved in the United States in June 2023. Beyond Roctavian, there are ongoing pivotal trials of additional AAV vectors for HA, others that are progressing through preclinical development or early-phase clinical trial, as well as non-AAV approaches in clinical development. This review focuses on the clinical development of Roctavian for which the collective clinical trials represent the largest body of work thus far available for any licensed AAV product. From this pioneering clinical development, several outstanding questions have emerged for which the answers will undoubtedly be important to the clinical adaptation of Roctavian and future efforts in HA gene therapy. Most notably, unexplained year-over-year declines in factor VIII (FVIII) expression after Roctavian treatment contrast with stable FVIII expression observed in other AAV HA gene therapy clinical trials with more modest initial FVIII expression. This observation has been qualitatively replicated in animal models that may permit mechanistic study. The development and approval of Roctavian is a landmark in HA therapeutics, although next-generation approaches are needed before HA gene therapy fulfills its promise of stable FVIII expression that normalizes hemostasis.
Smoking and vaping alter genes related to mechanisms of SARS-CoV-2 susceptibility and severity: a systematic review and meta-analysis
Authors: Bowsher Rachel , Marczylo Timothy H. , Gooch Karen , Bailey Alexis , Wright Matthew D. , Marczylo Emma L.
Published: July 2024

Background

Evidence for the impact of smoking on coronavirus disease 2019 (COVID-19) is contradictory, and there is little research on vaping. Here we provide greater clarity on mechanisms perturbed by tobacco cigarette, electronic cigarette and nicotine exposures that may impact the risks of infection and/or disease severity.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the Ovid and Web of Science databases were searched. Study design and exposure-induced gene expression changes were extracted. Each study was quality assessed and higher confidence scores were assigned to genes consistently changed across multiple studies following the same exposure. These genes were used to explore pathways significantly altered following exposure.

Results

125 studies provided data on 480 genes altered by exposure to tobacco cigarettes, e-cigarettes, nicotine or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Genes involved in both SARS-CoV-2 viral-entry and inflammation were changed following exposure. Pathway analysis revealed that many of those genes with high confidence scores are involved in common cellular processes relating to hyperinflammatory immune responses.

Conclusion

Exposure to tobacco cigarettes, e-cigarettes or nicotine may therefore impact initial host–pathogen interactions and disease severity. Smokers and vapers of e-cigarettes with nicotine could potentially be at increased risk of SARS-CoV-2 infection, associated cytokine storm, and acute respiratory distress syndrome. However, further research is required, particularly on e-cigarettes, to determine the biological mechanisms involved in perturbation of viral-entry genes and host–pathogen interactions and subsequent responses within the respiratory tract. This will improve our physiological understanding of the impact of smoking and vaping on COVID-19, informing public health advice and providing improved guidance for management of SARS-CoV-2 and other respiratory viruses.
Deep phenotyping of unaffected carriers of pathogenicBMPR2variants screened for pulmonary arterial hypertension
Authors: Tóth Eszter N. , Celant Lucas R. , Niglas Marili , Jansen Samara , Tramper Jelco , Baxan Nicoleta , Ashek Ali , Wessels Jeroen N. , Marcus J. Tim , Meijboom Lilian J. , Houweling Arjan C. , Nossent Esther J. , Aman Jurjan , Grynblat Julien , Perros Frédéric , Montani David , Vonk Noordegraaf Anton , Zhao Lan , de Man Frances S. , Bogaard Harm Jan
Published: July 2024

Introduction

Pathogenic variants in the gene encoding forBMPR2are a major genetic risk factor for heritable pulmonary arterial hypertension. Owing to incomplete penetrance, deep phenotyping of unaffected carriers of a pathogenicBMPR2variant through multimodality screening may aid in early diagnosis and identify susceptibility traits for future development of pulmonary arterial hypertension.

Methods

28 unaffected carriers (44±16 years, 57% female) and 21 healthy controls (44±18 years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging, transthoracic echocardiography, cardiopulmonary exercise testing and right heart catheterisation. Right ventricular pressure–volume loops were constructed to assess load-independent contractility and compared with a healthy control group. A transgenicBmpr2Δ71Ex1/+rat model was employed to validate findings from humans.

Results

Unaffected carriers had lower indexed right ventricular end-diastolic (79.5±17.6 mL·m−2versus62.7±15.3 mL·m−2; p=0.001), end-systolic (34.2±10.5 mL·m−2versus27.1±8.3 mL·m−2; p=0.014) and left ventricular end-diastolic (68.9±14.1 mL·m−2versus58.5±10.7 mL·m−2; p=0.007) volumes than control subjects.Bmpr2Δ71Ex1/+rats were also observed to have smaller cardiac volumes than wild-type rats. Pressure–volume loop analysis showed that unaffected carriers had significantly higher afterload (arterial elastance 0.15±0.06 versus0.27±0.08 mmHg·mL−1; p<0.001) and end-systolic elastance (0.28±0.07 versus0.35±0.10 mmHg·mL−1; p=0.047) in addition to lower right ventricular pulmonary artery coupling (end-systolic elastance/arterial elastance 2.24±1.03versus1.36±0.37; p=0.006). During the 4-year follow-up period, two unaffected carriers developed pulmonary arterial hypertension, with normal N-terminal pro-brain natriuretic peptide and transthoracic echocardiography indices at diagnosis.

Conclusion

UnaffectedBMPR2mutation carriers have an altered cardiac phenotype mimicked inBmpr2Δ71Ex1/+transgenic rats. Future efforts to establish an effective screening protocol for individuals at risk for developing pulmonary arterial hypertension warrant longer follow-up periods.
Medical hypnosis mitigates laboratory dyspnoea in healthy humans: a randomised, controlled experimental trial
Authors: Morélot-Panzini Capucine , Arveiller-Carvallo Cécile , Rivals Isabelle , Wattiez Nicolas , Lavault Sophie , Brion Agnès , Serresse Laure , Straus Christian , Niérat Marie-Cécile , Similowski Thomas
Published: July 2024

Question

Dyspnoea persisting despite treatments of underlying causes requires symptomatic approaches. Medical hypnosis could provide relief without the untoward effects of pharmacological approaches. We addressed this question through experimentally induced dyspnoea in healthy humans (inspiratory threshold loading (excessive inspiratory effort) and carbon dioxide stimulation (air hunger)).

Material and methods

20 volunteers (10 women, aged 21–40 years) were studied on four separate days. The order of the visits was randomised in two steps: firstly, the “inspiratory threshold loading first”versus“carbon dioxide first” group (n=10 in each group); secondly, the “medical hypnosis first”versus“visual distraction first” subgroup (n=5 in each subgroup). Each visit comprised three 5-min periods (reference, intervention, washout) during which participants used visual analogue scales (VAS) to rate the sensory and affective dimensions of dyspnoea, and after which they completed the Multidimensional Dyspnea Profile.

Results

Medical hypnosis reduced both dimensions of dyspnoea significantly more than visual distraction (inspiratory threshold loading: sensory reduction after 5 min 34% of full VASversus8% (p=0.0042), affective reduction 17.6%versus2.4% (p=0.044); carbon dioxide: sensory reduction after 5 min 36.9%versus3% (p=0.0015), affective reduction 29.1%versus8.7% (p=0.0023)). The Multidimensional Dyspnea Profile showed more marked sensory effects during inspiratory threshold loading and more marked affective effects during carbon dioxide stimulation.

Answer to the question

Medical hypnosis was more effective than visual distraction at attenuating the sensory and affective dimensions of experimentally induced dyspnoea. This provides a strong rationale for clinical studies of hypnosis in persistent dyspnoea patients.
Barriers to and enablers of physical activity and its association with daily steps after hospitalisation for a COPD exacerbation: what patients say matters
Authors: Valeiro Beatriz , Rodríguez Esther , Ferrer Jaume , Pasarín Alejandro , Ibañez Jordi , Ramon María Antonia
Published: July 2024

Introduction

Exacerbations of COPD decrease physical activity. Physical activity interventions after these events are desirable but have had mixed results. Understanding the barriers to and enablers of physical activity may help to improve the results of these interventions. We aimed to assess the barriers to and enablers of physical activity after COPD exacerbation and their association with daily steps.

Methods

We carried out a cross-sectional analysis of patients with COPD enrolled during a hospitalisation for an exacerbation. Physical activity was measured with an accelerometer for 7 days after discharge. Patients completed anad hoc6-point Likert scale questionnaire about 13 barriers to and nine enablers of physical activity. We analysed the association between each item and patients’ daily step counts.

Results

46 patients with a mean±sdforced expiratory volume in 1 s of 48.6±15.9% predicted completed the assessments. They were 65±10 years old, spent 8±2 days hospitalised and walked 5633±3314 steps·day−1after discharge. The patients who reported “breathlessness” as a barrier (≥2 out of 6 points on the Likert scale) took statistically fewer daily steps (median (25th–75th centile) 3813 steps·day−1(2664–5639 steps·day−1)versus5549 steps·day−1(3692–9984 steps·day−1), p=0.034). There was a similar finding for those who reported “low mood” as a barrier (≥2 out of 6 points) (3813 steps·day−1(2456–5471 steps·day−1)versus5426 steps·day−1(3612–8942 steps·day−1), p=0.047). If they considered “physical activity as healthy” as an enabler, they walked statistically more (5085 steps·day−1(3538–8703 steps·day−1)versus2760 steps·day−1(2271–5298 steps·day−1), p=0.031).

Conclusion

Some barriers to and enablers of physical activity reported by patients after a COPD exacerbation relate to daily steps. Assessing physical activity barriers and enablers could be useful to improve future physical activity interventions after these events.
Do-not-attempt-resuscitation decision making: physicians’ recommendations differ from the GO-FAR score predictions
Authors: Alao David Olukolade , Abraham Snaha , Dababneh Emad , Roby Roxanne , Farid Mohammed , Mohammed Nada , Rojas-Perilla Natalia , Cevik Arif Alper
Published: July 2024

Background and aim

In-hospital cardiac arrest (IHCA) is a major cause of mortality globally, and over 50% of the survivors will require institutional care as a result of poor neurological outcome. It is important that physicians discuss the likely outcome of resuscitation with patients and families during end-of-life discussions to help them with decisions about cardiopulmonary resuscitation. We aim to compare three consultants’ do-not-resuscitate (DNR) decisions with the GO-FAR score predictions of the probability of survival with good neurological outcomes following in-hospital cardiac arrest (IHCA).

Methods

This is a retrospective study of all patients 18 years or older placed on a DNR order by a consensus of three consultants in a tertiary institution in the United Arab Emirates over 12 months. Patients’ socio-demographics and the GO-FAR variables were abstracted from the electronic medical records. We applied the GO-FAR score and the probability of survival with good neurological outcomes for each patient.

Results

A total of 788 patients received a DNR order, with a median age of 71 years and a majority being males and expatriates. The GO-FAR model categorized 441 (56%) of the patients as having a low or very low probability of survival and 347 (44%) as average or above. There were 219 patients with a primary diagnosis of cancer, of whom 148 (67.6%) were in the average and above-average probability groups. There were more In-hospital deaths among patients in the average and above-average probability of survival group compared with those with very low and low probability (243 (70%) versus 249 (56.5%) (P < 0.0001)). The DNR patients with an average or above average chance of survival by GO-FAR score were more likely to be expatriates, oncology patients, and did not have sepsis.

Conclusions

The GO-FAR score provides a guide for joint decision-making on the possible outcomes of CPR in the event of IHCA. The physicians’ recommendation and the ultimate patient’s resuscitation choice may differ due to more complex contextual medico-social factors.
Emotion-focused therapy for women with premenstrual dysphoric disorder: a randomized clinical controlled trial
Authors: Dehnavi Saeideh Izadi , Mortazavi Seyede Salehe , Ramezani Mohammad Arash , Gharraee Banafshe , Ashouri Ahmad
Published: July 2024

Background

Premenstrual dysphoric disorder (PMDD) is a debilitating condition, affecting women of reproductive age. It is characterized by severe periodic physical and psychological symptoms, which end after the onset of menstruation. This study aimed to evaluate the effectiveness of emotion-focused therapy (EFT) for PMDD patients.

Methods

A total of 48 PMDD women, in the age range of 18–44 years, were randomly assigned to two intervention and control groups. The intervention group participated in 16 weeks of EFT treatment, while the control group was selected based on the waiting list (waitlist control group) and followed-up after three months. Forty-four patients finally completed this study. The participants completed the Premenstrual Syndrome Screening Tool (PSST), Difficulties in Emotion Regulation Scale (DERS), and Depression Anxiety Stress Scale-21 (DASS-21) in the first premenstrual period before treatment, the first premenstrual period after treatment, and the premenstrual period three months after treatment.

Results

Based on the repeated measure analysis of variances, the total score of DERS and the total score of PSST decreased significantly (P < 0.05). Also, in DASS-21, the scores of depression and stress subscales reduced significantly (P < 0.05), while there was no significant decrease in the score of anxiety subscale (P > 0.05).

Conclusion

Based on the present results, EFT can be an effective treatment for alleviating the symptoms of PMDD. This treatment can reduce the emotion regulation difficulties of women with PMDD and alleviate the symptoms of depression and stress.

Trial registration

Iranian Registry of Clinical Trials, IRCT ID: IRCT20220920055998N1, Registered on: 12/2/2023.
Collaboration in providing intimate-partner violence services to women with disabilities
Authors: Namatovu Fredinah , Ineland Jens
Published: July 2024

Background

There is a consensus among scholars, policymakers, and implementers that addressing the complex nature of intimate partner violence (IPV) requires a collaborative response. However, there is limited literature on how various professionals work collaboratively to address the needs of women with disabilities who experience IPV. This study combines the perspectives of women with disabilities and those of professionals to understand collaboration in providing IPV services to women with disabilities.

Methods

Twenty-nine in-depth interviews were conducted with 18 IPV service providers and 11 women with disabilities. The data were analyzed using reflective thematic analysis.

Results

The findings are presented under three themes: the first shows a consensus among different IPV service providers and disabled women on the importance of collaboration when supporting victims of IPV with disabilities; the second depicts the common ways in which collaboration occurs when supporting women with disabilities; and the third illuminates the critical elements that boost effective collaboration.

Conclusion

Supporting IPV victims with disabilities requires active collaboration at both an internal and external level. Strengthening collaboration among different actors requires trust, specified roles, and the allocation of adequate resources.
Unravelling factors influencing demand for modern contraception and evaluating coverage progress since 2015 in Ethiopia, Kenya, and Nigeria: insights from multilevel and geostatistical modelling
Authors: Khundi McEwen , Mzembe Themba , Ngwira Tabitha , Mankhwala Chifuniro S , Chifungo Chimwemwe , Peterson Maame B , Vellemu Ruth , Madise Nyovani J , Chipeta Michael G
Published: July 2024

Introduction

The United Nations established the Sustainable Development Goals (SDGs) in 2015 to enhance global development. In this study, we examine an SDG indicator: the percentage of women aged 15–49 whose family planning needs are met by modern contraception (mDFPS). We evaluate both the factors influencing its coverage and its progress since 2015.

Methods

We used nationally representative surveys data (Demographic and Health Surveys (DHS) and Performance Monitoring for Action (PMA)) from Ethiopia, Kenya, and Nigeria. We assessed predictors of mDFPS. We also computed mDFPS coverage across countries and subnational areas, assessing coverage changes from the SDGs onset to the most recent period, using a Bayesian model-based geostatistical approach. We assessed whether the subnational areas exceeded the minimum recommended WHO mDFPS coverage of 75%.

Results

Varied individual and community-level determinants emerged, highlighting the countries’ uniqueness. Factors such as being part of a female-headed household, and low household wealth, lowered the odds of mDFPS, while rural-residence had low odds only in Ethiopia and Nigeria. The results indicate mDFPS stagnation in most administrative areas across the three countries. Geographic disparities persisted over time, favouring affluent regions. The predicted posterior proportion of mDFPS and exceedance probability (EP) for WHO target for Ethiopia was 39.85% (95% CI: [4.51, 83.01], EP = 0.08) in 2016 and 46.28% (95% CI: [7.15, 85.99], EP = 0.13) in 2019. In Kenya, the adjusted predicted proportion for 2014 was 30.19% (95% CI: [2.59, 80.24], EP = 0.06) and 44.16% (95%CI: [9.35, 80.24], EP = 0.13) in 2022. In Nigeria, the predicted posterior proportion of mDFPS was 17.91% (95% CI: [1.24, 61.29], EP = 0.00) in 2013, and it was 23.08% (95% CI: [1.80, 56.24], EP = 0.00) in 2018. None of the sub-national areas in Ethiopia and Nigeria exceeded the WHO target. While 9 out of 47 counties in Kenya in 2022 exceeded the WHO mDFPS target.

Conclusion

The study unveils demographic, geographic, and socioeconomic mDFPS disparities, signalling progress and stagnation across administrative areas. The findings offer policymakers and governments insights into targeting interventions for enhanced mDFPS coverage. Context-specific strategies can address local needs, aiding SDG attainment.
The impact of sleep quality on emotion regulation difficulties in adolescents: a chained mediation model involving daytime dysfunction, social exclusion, and self-control
Authors: Wang Wenjuan , Zhu Yuqiong , Yu Hang , Wu Chengcong , Li Tiancheng , Ji Chenguang , Jiang Yulian , Ding Dongyan
Published: July 2024

Objective

Previous studies have revealed associations between sleep quality and mental health, yet the comprehensive role of sleep quality, daytime dysfunction, social exclusion, and self-control in difficulties with emotion regulation remains unclear. This study aimed to elucidate how sleep quality affects emotion regulation difficulties among middle school students through pathways involving daytime dysfunction, social exclusion, and self-control, thereby providing a more comprehensive theoretical basis for mental health interventions.

Methods

Utilizing the pittsburgh sleep quality index, the adolescent social exclusion scale, the brief self-control scale, and emotion regulation scale-short form, we assessed 1067 students randomly selected from four middle schools from October to November 2023. After the removal of extreme values (those exceeding 3 standard deviations), 806 students were retained for data analysis.

Results

Our findings indicate that poor sleep quality significantly contributes to increased daytime dysfunction(β = 0.86, SE = 0.07, p < .001), which in turn affects social exclusion(β = 0.60, SE = 0.16, p < 0 0.001), self-control abilities(β = 1.27, SE = 0.16, p < .001) and emotion regulation difficulties(β = 1.56, SE = 0.30, p < .001). Social exclusion mediates the relationship between sleep quality and emotion regulation difficulties(Estimate = 0.11, SE = 0.04, 95% CI [0.04, 0.20] ).

Conclusion

The aim of this study is to provide new insights into the development of effective intervention measures to improve sleep and mental health in adolescents.
Administration of the American Board of Anesthesiology’s virtual APPLIED Examination: successes, challenges, and lessons learned
Authors: Keegan Mark T. , Harman Ann E. , McLoughlin Thomas M. , Macario Alex , Deiner Stacie G. , Gaiser Robert R. , Warner David O. , Suresh Santhanam , Sun Huaping
Published: July 2024

In response to the COVID-19 pandemic, the American Board of Anesthesiology transitioned from in-person to virtual administration of its APPLIED Examination, assessing more than 3000 candidates for certification purposes remotely in 2021. Four hundred examiners were involved in delivering and scoring Standardized Oral Examinations (SOEs) and Objective Structured Clinical Examinations (OSCEs). More than 80% of candidates started their exams on time and stayed connected throughout the exam without any problems. Only 74 (2.5%) SOE and 45 (1.5%) OSCE candidates required rescheduling due to technical difficulties. Of those who experienced “significant issues”, concerns with OSCE technical stations (interpretation of monitors and interpretation of echocardiograms) were reported most frequently (6% of candidates). In contrast, 23% of examiners “sometimes” lost connectivity during their multiple exam sessions, on a continuum from minor inconvenience to inability to continue. 84% of SOE candidates and 89% of OSCE candidates described “smooth” interactions with examiners and standardized patients/standardized clinicians, respectively. However, only 71% of SOE candidates and 75% of OSCE candidates considered themselves to be able to demonstrate their knowledge and skills without obstacles. When compared with their in-person experiences, approximately 40% of SOE examiners considered virtual evaluation to be more difficult than in-person evaluation and believed the remote format negatively affected their development as an examiner. The virtual format was considered to be less secure by 56% and 40% of SOE and OSCE examiners, respectively. The retirement of exam materials used virtually due to concern for compromise had implications for subsequent exam development. The return to in-person exams in 2022 was prompted by multiple factors, especially concerns regarding standardization and security. The technology is not yet perfect, especially for testing in-person communication skills and displaying dynamic exam materials. Nevertheless, the American Board of Anesthesiology’s experience demonstrated the feasibility of conducting large-scale, high-stakes oral and performance exams in a virtual format and highlighted the adaptability and dedication of candidates, examiners, and administering board staff.
Dual inhibition of SUMOylation and MEK conquers MYC-expressing KRAS-mutant cancers by accumulating DNA damage
Authors: Kotani Hiroshi , Oshima Hiroko , Boucher Justin C. , Yamano Tomoyoshi , Sakaguchi Hiroyuki , Sato Shigeki , Fukuda Koji , Nishiyama Akihiro , Yamashita Kaname , Ohtsubo Koushiro , Takeuchi Shinji , Nishiuchi Takumi , Oshima Masanobu , Davila Marco L. , Yano Seiji
Published: July 2024

Background

KRAS mutations frequently occur in cancers, particularly pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. Although KRASG12C inhibitors have recently been approved, effective precision therapies have not yet been established for all KRAS-mutant cancers. Many treatments for KRAS-mutant cancers, including epigenome-targeted drugs, are currently under investigation. Small ubiquitin-like modifier (SUMO) proteins are a family of small proteins covalently attached to and detached from other proteins in cells via the processes called SUMOylation and de-SUMOylation. We assessed whether SUMOylation inhibition was effective in KRAS-mutant cancer cells.

Methods

The efficacy of the first-in-class SUMO-activating enzyme E inhibitor TAK-981 (subasumstat) was assessed in multiple human and mouse KRAS-mutated cancer cell lines. A gene expression assay using a TaqMan array was used to identify biomarkers of TAK-981 efficacy. The biological roles of SUMOylation inhibition and subsequent regulatory mechanisms were investigated using immunoblot analysis, immunofluorescence assays, and mouse models.

Results

We discovered that TAK-981 downregulated the expression of the currently undruggable MYC and effectively suppressed the growth of MYC-expressing KRAS-mutant cancers across different tissue types. Moreover, TAK-981-resistant cells were sensitized to SUMOylation inhibition via MYC-overexpression. TAK-981 induced proteasomal degradation of MYC by altering the balance between SUMOylation and ubiquitination and promoting the binding of MYC and Fbxw7, a key factor in the ubiquitin–proteasome system. The efficacy of TAK-981 monotherapy in immunocompetent and immunodeficient mouse models using a mouse-derived CMT167 cell line was significant but modest. Since MAPK inhibition of the KRAS downstream pathway is crucial in KRAS-mutant cancer, we expected that co-inhibition of SUMOylation and MEK might be a good option. Surprisingly, combination treatment with TAK-981 and trametinib dramatically induced apoptosis in multiple cell lines and gene-engineered mouse-derived organoids. Moreover, combination therapy resulted in long-term tumor regression in mouse models using cell lines of different tissue types. Finally, we revealed that combination therapy complementally inhibited Rad51 and BRCA1 and accumulated DNA damage.

Conclusions

We found that MYC downregulation occurred via SUMOylation inhibition in KRAS-mutant cancer cells. Our findings indicate that dual inhibition of SUMOylation and MEK may be a promising treatment for MYC-expressing KRAS-mutant cancers by enhancing DNA damage accumulation.
Tezepelumab for refractory eosinophilic granulomatosis with polyangiitis-related asthma
Authors: Vincent-Galtié Nina , Marquant Quentin , Catherinot Emilie , Ackermann Felix , Magnan Antoine , Tcherakian Colas , Groh Matthieu
Published: July 2024

Conventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA.
Targeting CSF1R in myeloid-derived suppressor cells: insights into its immunomodulatory functions in colorectal cancer and therapeutic implications
Authors: Tong Xin , Qiao Shifeng , Dong Zhe , Zhao Xiaohui , Du Xiaxia , Niu Wei
Published: July 2024

Objective

This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination.

Methods

Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses.

Results

CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors.

Conclusion

CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.
Ultrasound-responsive Bi2MoO6-MXene heterojunction as ferroptosis inducers for stimulating immunogenic cell death against ovarian cancer
Authors: Cheng Shuangshuang , Zhou Ting , Luo Yue , Zhang Jun , Dong Kejun , Zhang Qi , Shu Wan , Zhang Tangansu , Zhang Qian , Shi Rui , Yao Yuwei , Wang Hongbo
Published: July 2024

Background

Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis.

Results

In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi2MoO6-MXene) to induce ferroptosis. A Schottky heterojunction between Bi2MoO6 (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron–hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity.

Conclusion

We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway.

Graphical Abstract
Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration
Authors: Lei Haoqi , Sun Jiwei , Dai Zhiyin , Wo Keqi , Zhang Junyuan , Wang Yifan , Zhao Baoying , Fan Wenjie , Wang Jinyu , Shi Yunsong , Yang Cheng , Su Bin , Luo Zhiqiang , Wu Junjie , Chen Lili , Chu Yingying
Published: July 2024

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Graphical Abstract