bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Recent Standing, Moving, or Sitting on Daytime Ambulatory Blood Pressure
Authors: Barone Gibbs Bethany , Muldoon Matthew F. , Conroy Molly B. , Paley Joshua L. , Shimbo Daichi , Perera Subashan
Published: August 2023

Background

There are no recommendations for being seated versus nonseated during ambulatory blood pressure (BP) monitoring (ABPM). The authors examined how recent standing or moving versus sitting affect average daytime BP on ABPM.

Methods and Results

This analysis used baseline assessments from a clinical trial in desk workers with office systolic BP (SBP) 120 to 159 mm Hg or diastolic BP (DBP) 80 to 99 mm Hg. ABPM was measured every 30 minutes with a SunTech Medical Oscar 2 monitor. Concurrent posture (standing or seated) and moving (steps) were measured via a thigh‐worn accelerometer. Linear regression determined within‐person BP variability explained (
R
2
) by standing and steps before ABPM readings. Mean daytime BP and the prevalence of mean daytime BP >135/85 mm Hg from readings after sitting (seated) or after recent standing or moving (nonseated) were compared with all readings. Participants (n=266, 59% women; age, 45.2±11.6 years) provided 32.5±3.9 daytime BP readings. Time standing and steps before readings explained variability up to 17% for daytime SBP and 14% for daytime DBP. Using the 5‐minute prior interval, seated SBP/DBP was lower (130.8/79.7 mm Hg,
P
<0.001) and nonseated SBP/DBP was higher (137.8/84.3 mm Hg,
P
<0.001) than mean daytime SBP/DBP from all readings (133.9/81.6 mm Hg). The prevalence of mean daytime SBP/DBP ≥135/85 mm Hg also differed: 38.7% from seated readings, 70.3% from nonseated readings, and 52.6% from all readings (
P
<0.05).

Conclusions

Daytime BP was systematically higher after standing and moving compared with being seated. Individual variation in activity patterns could influence the diagnosis of high BP using daytime BP readings on ABPM.
Enclosing the Open Fields
Authors: Gehrke Louisa-Dorothea
Published: August 2023

Early modern natural history was both characterized by naturalists collecting jointly on excursions and by the employment of paper technologies in the exchange of information and objects. Evaluating a sample of Matthias Ernst Boretius’s correspondence with Johann Philipp Breyne (Gotha research library) as well as Jacob Breyne’s 1659 herbarium as a gift to Hieronymus van Beverningh (Naturalis Biodiversity Center Leiden), this paper argues that naturalists made creative use of those technologies as substitutes for joint outings. It analyzes the specific characteristics of the letter and the herbarium as instruments for both distance interaction and self-presentation, considering the relationship between sender and addressee, and the aims the authors pursued with their respective media. As the herbarium has not been fully considered before this background yet, the paper contributes to its understanding as a means of naturalist communication.
Differential Forgiveness Perspectives and Their Implications on Bangsamoro-Christian Conflict Resolution
Authors: Labor Paul Danielle P. , Gastardo-Conaco Maria Cecilia C.
Published: August 2023

The article explored intergroup perspectives among Bangsamoro and Christian group members to determine their impact on forgiveness-based peace initiatives and conflict resolution. It adopts a qualitative approach by analyzing thematically four (4) focus group discussions. Bangsamoro participants’ themes on Intergroup Forgiveness as a Process of Negotiation and Pride as Key Factor in the Process of Intergroup Forgiveness stress socio-religious and political leaders’ roles including that of cultural values such as maratabat (honor) and sabar (silent forbearance). Christian participants’ Intergroup Forgiveness as an Outcome through Discussion/Communication theme emphasizes understanding and pride’s impact on the forgiveness process. These findings bring to awareness the complexity of integrating intergroup forgiveness in current peacebuilding interventions.
The Poetics of Persianate Disaffiliation: Recusative Gestures for a Royal Genre
Authors: Hodgkin Samuel
Published: August 2023

Across the Persianate regions of late-nineteenth and early-twentieth-century Eurasia, the discourse of modernization had a deep, perhaps even dominant aesthetic dimension. Apparently disparate anxieties about oriental indolence, homosexuality and unmanliness, flattery and unmeaning speech, and submission to despots all may be understood as elements of a coherent critique of a single literary mode: taghazzul. Insofar as ghazal was a “royal genre” (Ireneusz Opacki), it provided the formal-aesthetic framing for numerous literary and speech genres, and thus for the social and political order. In case studies from across the Persianate zone, this article considers how writers’ refusal of taghazzul, or its excision from their texts, became a recognizable gesture of disaffiliation from the Persianate. In the resulting reordering of the literary field, taghazzul took on new functions in relation to the Western category of lyric.
Bacterial Vaginosis Treatment Patterns, Associated Complications, and Health Care Economic Burden of Women With Medicaid Coverage in the United States
Authors: Watkins Eren , Chow Clifton M. , Lingohr-Smith Melissa , Lin Jay , Yong Candice , Tangirala Krishna , Collins Kevin , Li James , Brooks Roy , Amico Jennifer
Published: August 2023

Background

Bacterial vaginosis (BV) is a highly prevalent vaginal infection.

Objectives

Primary objectives of this study were to examine treatment patterns among female patients with Medicaid coverage who were diagnosed with incident BV, the frequency of BV-associated complications, and health care resource utilization (HCRU) and associated costs of incident BV and its recurrence. Secondary objectives were to identify predictors of total all-cause health care costs and number of treatment courses.

Methods

Female patients aged 12-49 years with an incident vaginitis diagnosis and ≥1 pharmacy claim for a BV medication were selected from the Merative MarketScan Medicaid database (2017-2020). Additional treatment courses were evaluated during a ≥12-month follow-up period, in which new cases of BV-associated complications and HCRU and the associated costs were also measured. Generalized linear models were used to identify baseline predictors of total all-cause health care costs and number of treatment courses.

Results

An incident vaginitis diagnosis and ≥1 BV medication claim were present in 114 313 patients (mean age: 28.4 years; 48.6% black). During the follow-up, 56.6% had 1 treatment course, 24.9% had 2, 10.2% had 3, and 8.3% had ≥4; 43.4% had BV recurrence. Oral metronidazole (88.5%) was the most frequently prescribed medication. Nearly 1 in 5 had a new occurrence of a BV-associated complication; most (76.6%) were sexually transmitted infections (STIs). Total all-cause and BV-related costs averaged $5794 and $300, respectively, per patient; both increased among those with more treatment courses. Older age, pregnancy, comorbidity, any STIs, postprocedural gynecological infection (PGI), and infertility were predictive of higher total all-cause health care costs, while race/ethnicity other than white was predictive of lower costs. Older age, black race, any STIs, pelvic inflammatory disease, and PGI were predictive of >1 treatment courses.

Conclusion and Relevance

The high recurrence of BV represents an unmet need in women’s health care and better treatments are necessary.
The Effect of Asymmetric Intersexual Selection Power Perception on the Choice Deferral Behavior of Men and Women
Authors: Jin Cheng-wen , Chen Rui
Published: August 2023

Consumers always delay their choices, which can cause companies to suffer tremendous losses. One reason for such delay is a lack of confidence. Confidence in consumer decision-making can stem from many sources, including social power. In this research, we find that selection power with regard to choosing a romantic mate increases consumers’ decision confidence and, in turn, decreases choice deferral. We define the concept of intersexual selection power (ISP), and propose certain factors that can induce individuals’ asymmetric ISP. We conducted four studies to explore four factors that could influence consumers’ ISP perceptions (sex, mating cues, sex ratio, and mate value) and the effects of such power perception on choice deferral. The results showed that individuals with high ISP perception have more decision confidence and a lower choice deferral rate than individuals with low ISP perception regardless of the way in which choice deferral is measured.
Identification of CDK gene family and functional analysis of CqCDK15 under drought and salt stress in quinoa
Authors: Wang Wangtian , Liu Wenyu , Wang Baoqiang
Published: August 2023

as one of the oldest cultivated crops in the world, quinoa has been widely valued for its rich nutritional value and green health. In this study, 22 CDK genes (CqCDK01-CqCDK22) were identified from quinoa genome using bioinformatics method. The number of amino acids was 173–811, the molecular weight was 19,554.89 Da-91,375.70 Da, and the isoelectric point was 4.57–9.77. The phylogenetic tree divided 21 CqCDK genes into six subfamilies, the gene structure showed that 12 (54.5%) CqCDK genes (CqCDK03, CqCDK04, CqCDK05, CqCDK06, CqCDK07, CqCDK11, CqCDK14, CqCDK16, CqCDK18, CqCDK19, CqCDK20 and CqCDK21) had UTR regions at 5’ and 3’ ends. Each CDK protein had different motifs (3–9 motifs), but the genes with the same motifs were located in the same branch. Promoter analysis revealed 41 cis-regulatory elements related to plant hormones, abiotic stresses, tissue-specific expression and photoresponse. The results of real-time fluorescence quantitative analysis showed that the expression level of some CDK genes was higher under drought and salt stress, which indicated that CDK genes could help plants to resist adverse environmental effects. Subcellular localization showed that CqCDK15 gene was localized to the nucleus and cytoplasm, and transgenic plants overexpressing CqCDK15 gene showed higher drought and salt tolerance compared to the controls. Therefore, CDK genes are closely related to quinoa stress resistance. In this study, the main functions of quinoa CDK gene family and its expression level in different tissues and organs were analyzed in detail, which provided some theoretical support for quinoa stress-resistant breeding. Meanwhile, this study has important implications for further understanding the function of the CDK gene family in quinoa and our understanding of the CDK family in vascular plant.
Aberrant activation of five embryonic stem cell-specific genes robustly predicts a high risk of relapse in breast cancers
Authors: Jacquet Emmanuelle , Chuffart Florent , Vitte Anne-Laure , Nika Eleni , Mousseau Mireille , Khochbin Saadi , Rousseaux Sophie , Bourova-Flin Ekaterina
Published: August 2023

Background

In breast cancer, as in all cancers, genetic and epigenetic deregulations can result in out-of-context expressions of a set of normally silent tissue-specific genes. The activation of some of these genes in various cancers empowers tumours cells with new properties and drives enhanced proliferation and metastatic activity, leading to a poor survival prognosis.

Results

In this work, we undertook an unprecedented systematic and unbiased analysis of out-of-context activations of a specific set of tissue-specific genes from testis, placenta and embryonic stem cells, not expressed in normal breast tissue as a source of novel prognostic biomarkers. To this end, we combined a strict machine learning framework of transcriptomic data analysis, and successfully created a new robust tool, validated in several independent datasets, which is able to identify patients with a high risk of relapse. This unbiased approach allowed us to identify a panel of five biomarkers, DNMT3B, EXO1, MCM10, CENPF and CENPE, that are robustly and significantly associated with disease-free survival prognosis in breast cancer. Based on these findings, we created a new Gene Expression Classifier (GEC) that stratifies patients. Additionally, thanks to the identified GEC, we were able to paint the specific molecular portraits of the particularly aggressive tumours, which show characteristics of male germ cells, with a particular metabolic gene signature, associated with an enrichment in pro-metastatic and pro-proliferation gene expression.

Conclusions

The GEC classifier is able to reliably identify patients with a high risk of relapse at early stages of the disease. We especially recommend to use the GEC tool for patients with the luminal-A molecular subtype of breast cancer, generally considered of a favourable disease-free survival prognosis, to detect the fraction of patients undergoing a high risk of relapse.
A survey of surgical patients’ perspectives and preferences towards general anesthesia techniques and shared-decision making
Authors: Pennington Bethany R. Tellor , Politi Mary C , Abdallah Arbi Ben , Janda Allison M. , Eshun-Wilsonova Ingrid , deBourbon Nastassjia G. , Siderowf Lilly , Klosterman Heidi , Kheterpal Sachin , Avidan Michael S.
Published: August 2023

Background

The decision about which type of general anesthetic to administer is typically made by the clinical team without patient engagement. This study examined patients’ preferences, experiences, attitudes, beliefs, perceptions, and perceived social norms about anesthesia and about engaging in the decision regarding general anesthetic choice with their clinician.

Methods

We conducted a survey in the United States, sent to a panel of surgical patients through Qualtrics (Qualtrics, Provo, UT) from March 2022 through May 2022. Questions were developed based on the Theory of Planned Behavior and validated measures were used when available. A patient partner who had experienced both intravenous and inhaled anesthesia contributed to the development and refinement of the questions.

Results

A total of 806 patients who received general anesthesia for an elective procedure in the last five years completed the survey. 43% of respondents preferred a patient-led decision making role and 28% preferred to share decision making with their clinical team, yet only 7.8% reported being engaged in full shared decision making about the anesthesia they received. Intraoperative awareness, pain, nausea, vomiting and quickly returning to work and usual household activities were important to respondents. Waking up in the middle of surgery was the most commonly reported concern, despite this experience being reported only 8% of the time. Most patients (65%) who searched for information about general anesthesia noted that it took a lot of effort to find the information, and 53% agreed to feeling frustrated during the search.

Conclusions

Most patients prefer a patient-led or shared decision making process when it comes to their anesthetic care and want to be engaged in the decision. However, only a small percentage of patients reported being fully engaged in the decision. Further studies should inform future shared decision-making tools, informed consent materials, educational materials and framing of anesthetic choices for patients so that they are able to make a choice regarding the anesthetic they receive.
T2-weighted imaging and dynamic contrast‑enhanced imaging in predicting the prognosis in patients with acute-on-chronic liver failure
Authors: Du Yan Ni , Guan Chun Shuang , Lv Zhi Bin , Xue Ming , Xing Yu Xue , Xie Ru Ming
Published: August 2023

Background

Acute-on-chronic liver failure (ACLF) is a syndrome with high 28- and 90-day mortality rates. Magnetic resonance imaging (MRI) has been widely used to diagnose and evaluate liver disease. Our purpose is to determine the value of the imaging features derived from Gd-DTPA-enhanced MRI for predicting the poor outcome of patients with ACLF and develop a clinically practical radiological score.

Methods

This retrospective study comprised 175 ACLF patients who underwent Gd-DTPA-enhanced abdominal MRI from January 2017 to December 2021. The primary end-point was 90-day mortality. Imaging parameters, such as diffuse hyperintense of the liver on T2WI, patchy enhancement of the liver at the arterial phase, uneven enhancement of the liver at the portal vein phase, gallbladder wall edema, periportal edema, ascites, esophageal and gastric varix, umbilical vein patefac, portal vein thrombosis, and splenomegaly were screened. Cox proportional hazard regression models were used to evaluate prognostic factors and develop a prediction model. The accuracy of the model was evaluated by receiver operating characteristic (ROC) curves.

Results

During the follow-up period, 31 of the 175 ACLF patients died within 90 days. In the multivariate analysis, three imaging parameters were independently associated with survival: diffuse hyperintense on T2WI (p = 0.007; HR = 3.53 [1.40–8.89]), patchy enhancement at the arterial phase (p = 0.037; HR = 2.45 [1.06–5.69]), moderate ascites (vs. mild) (p = 0.006; HR = 4.12 [1.49–11.36]), and severe ascites (vs. mild) (p = 0.005; HR = 4.29 [1.57–11.71]). A practical radiological score was proposed, based on the presence of diffuse hyperintense (7 points), patchy enhancement (5 points), and ascites (6, 8, and 8 points for mild, moderate, and severe, respectively). Further analysis showed that a cut-off at 14 points was optimum to distinguish high-risk (score > 14) from the low-risk group (score ≤ 14) for 90-day survival and demonstrated a mean area under the ROC curve of 0.774 in ACLF patients.

Conclusions

Gd-DTPA-enhanced MR imaging features can predict poor outcomes in patients with ACLF, based on which we proposed a clinically practical radiological score allowing stratification of the 90-day survival.
An exploration of health workers’ experiences in providing bereavement care to mothers following a stillbirth: results from a subnational level health system in Uganda
Authors: Ssegujja Eric , Ddumba Isaac , Andipatin Michelle
Published: August 2023

Background

Stillbirth is a profound emotion-laden event to the mothers and health workers who provide care due to its sudden and unexpected occurrence. Health workers offering support in regions shouldering the highest-burden experience providing support to a stillbirth mother in their professional lifetime. However, their experiences seldom get documented as much of the focus is on mothers causing a dissonance between parental and clinical priorities. This study aimed to explore the health worker’s experiences in the provision of bereavement care to mothers following a stillbirth.

Methods

An exploratory cross-sectional qualitative study was undertaken on a purposively selected sample of key informants drawn from frontline health workers and health systems managers providing maternal health services at a subnational level health system in Uganda. An interview guide was used to collect data with the audio-recorded interviews transcribed using Microsoft office word. Atlas. ti a qualitative data management software aided in coding with analysis following a thematic content analysis technique.

Results

There was no specialised bereavement care provided due to inadequate skills, knowledge of content, resources and support supervision for the same. However, health workers improvised within the available resources to comfort mothers upon news of a stillbirth. Disclosure to mothers about the stillbirth loss often took the form of forewarnings, direct and sometimes delayed disclosure. A feeling of unpreparedness to initiate the disclosure process to the mother was common while the whole experience had an emotional effect on the health workers when establishing the cause, particularly for cases without clear risk factors. The emotional breakdown was often a reflexive response from the mothers which equally affected the care providers. Health workers engaged in comforting and rebuilding the mothers to transition through the loss and validate the loss. Efforts to identify the skills and health systems gaps for address were a common response targeted at improving the quality of maternal healthcare services to avert similar occurrences in the future.

Conclusion

Providing care to mothers after stillbirth was an emotional and challenging experience for health workers requiring different approaches to disclosure and provision of emotional support. The aspect of specialised bereavement care was lacking within the current response. Reflection of unpreparedness to handle the tasks demonstrates a deficit in the required skills. It is a critical gap missing hence calling for dedicated efforts to address it. Targeting efforts to improve health workers’ competencies and preparedness to manage grieving mothers is one way to approach it.
“I would not want the mechanic to direct me to an engine repair manual”: a qualitative analysis of provider perspectives on low-intensity treatments for patients on waiting lists
Authors: Peipert Allison , Adams Sydney , Lorenzo-Luaces Lorenzo
Published: August 2023

Background

Low-intensity treatments (LITs), such as bibliotherapy or online self-help, have the potential to reach more individuals than traditional face-to-face care by circumventing many of the common barriers to mental health treatment. Despite substantial research evidence supporting their usability and efficacy across several clinical presentations, prior work suggests that mental health providers rarely recommend LITs for patients waiting for treatment.

Methods

The present study analyzed provider open responses to a prompt asking about perceived barriers, thoughts, and comments related to additional treatment resources for patients on treatment waiting lists. We surveyed 141 practicing mental health providers, 65 of whom responded to an open text box with additional thoughts on using LITs for patients on treatment waiting lists. Responses were qualitatively coded using a thematic coding process.

Results

Qualitative outcomes yielded 11 codes: patient appropriateness, research evidence, feasibility, patient barriers, liability, patient personal contact, additional resources, positive attitudes, trust in programs, systemic problems, and downplaying distress.

Conclusions

Results suggest providers are predominantly concerned about the potential of suggesting a LIT that would be ultimately inappropriate for their patient due to a lack of assessment of the patient’s needs. Furthermore, providers noted ambiguity around the legal and ethical liability of recommending a LIT to someone who may not yet be a patient. Guidelines and standards for recommending LITs to patients on treatment waiting lists may help address ambiguity regarding their use in routine care.
The generation that lived during/participated in the war and the generation that inherited it: association between veterans PTSD and adult offspring’s emotional regulation strategies and alexithymia levels
Authors: El Moujabber Perla , Homsi Vanessa , Hallit Souheil , Obeid Sahar
Published: August 2023

Background

The long-term repercussions that war can have on both war generations and post-war generations lack in the literature. It is imperative to understand the psychological consequences of the Lebanese Civil War that took place from 1975 to 1990, on the offspring of those who took part in it. Accordingly, the objective of this study was to assess the association between paternal/veterans PTSD and adult offspring’s emotional regulation strategies and alexithymia levels, 30 years after the end of war.

Method

A cross-sectional study was carried out between September 2020 and September 2021 on a sample of 75 fathers of Lebanese former veterans and paramilitary veterans and their adult offspring. For the veterans and paramilitary veterans’ population, the PTSD Checklist was used to assess post-traumatic stress disorder, and the Combat Exposure Scale (CES) was used to measure the level of combat exposure. For the offspring population, the Emotional Regulation Questionnaire (ERQ) was used to assess emotional regulation strategies and the Toronto Alexithymia Scale (TAS) was used to measure the levels of alexithymia.

Results

Paternal PTSD (Beta = 10.19) was associated with higher levels of alexithymia in the offspring population. Regarding emotional regulation strategies, results showed that paternal PTSD (Beta = -3.24) was significantly associated with a decrease in the cognitive reappraisal score in the offspring. Also, paternal PTSD (Beta = 4.57) was significantly associated with an increase in expressive suppression score. Additionally, an older father’s age (Beta = 1.11) was significantly associated with an increased alexithymia score in the offspring. Moreover, results showed that paternal combat injuries (Beta = -4.24) were significantly associated with a decrease in the alexithymia score in the offspring population and an increase in the expressive suppression score (Beta = 3.28).

Conclusion

This study shows that fathers’ traumatic experience of war influences emotion regulation and alexithymia levels in their offspring. Longitudinal studies taking into account the age of the offspring at the time of onset of fathers’ symptoms may provide us with additional information to understand the influence of paternal PTSD on the emotional functioning of offspring during different phases of emotional development.
Using EMPOWER in daily life: a qualitative investigation of implementation experiences
Authors: Allan Stephanie , Beedie Sara , McLeod Hamish J. , Farhall John , Gleeson John , Bradstreet Simon , Morton Emma , Bell Imogen , Wilson-Kay Alison , Whitehill Helen , Matrunola Claire , Thomson David , Clark Andrea , Gumley Andrew
Published: August 2023

Background

Digital self-management tools blended with clinical triage and peer support have the potential to improve access to early warning signs (EWS) based relapse prevention in schizophrenia care. However, the implementation of digital interventions in psychosis can be poor. Traditionally, research focused on understanding how people implement interventions has focused on the perspectives of mental health staff. Digital interventions are becoming more commonly used by patients within the context of daily life, which means there is a need to understand implementation from the perspectives of patients and carers.

Methods

Semi-structured one-on-one interviews with 16 patients who had access to the EMPOWER digital self-management intervention during their participation in a feasibility trial, six mental health staff members who supported the patients and were enrolled in the trial, and one carer participant. Interviews focused on understanding implementation, including barriers and facilitators. Data were coded using thematic analysis.

Results

The intervention was well implemented, and EMPOWER was typically perceived positively by patients, mental health staff and the carer we spoke to. However, some patients reported negative views and reported ideas for intervention improvement. Patients reported valuing that the app afforded them access to things like information or increased social contact from peer support workers that went above and beyond that offered in routine care. Patients seemed motivated to continue implementing EMPOWER in daily life when they perceived it was creating positive change to their wellbeing, but seemed less motivated if this did not occur. Mental health staff and carer views suggest they developed increased confidence patients could self-manage and valued using the fact that people they support were using the EMPOWER intervention to open up conversations about self-management and wellbeing.

Conclusions

The findings from this study suggest peer worker supported digital self-management like EMPOWER has the potential to be implemented. Further evaluations of these interventions are warranted, and conducting qualitative research on the feasibility gives insight into implementation barriers and facilitators, improving the likelihood of interventions being usable. In particular, the views of patients who demonstrated low usage levels would be valuable.
Health aid displacement during a decade of conflict (2011–19) in Syria: an exploratory analysis
Authors: Alkhalil Munzer , Alaref Maher , Ekzayez Abdulkarim , Mkhallalati Hala , El Achi Nassim , Alzoubi Zedoun , Fouad Fouad , Alatraş Muhammed Mansur , Ramadan Abdulhakim , Mazumdar Sumit , Borghi Josephine , Patel Preeti
Published: August 2023

Background

Syria has been in continuous conflict since 2011, resulting in more than 874,000 deaths and 13.7 million internally displaced people (IDPs) and refugees. The health and humanitarian sectors have been severely affected by the protracted, complex conflict and have relied heavily on donor aid in the last decade. This study examines the extent and implications of health aid displacement in Syria during acute humanitarian health crises from 2011 to 2019.

Methods

We conducted a trend analysis on data related to humanitarian and health aid for Syria between 2011 and 2019 from the OECD’s Creditor Reporting System. We linked the data obtained for health aid displacement to four key dimensions of the Syrian conflict. The data were compared with other fragile states. We conducted a workshop in Turkey and key informants with experts, policy makers and aid practitioners involved in the humanitarian and health response in Syria between August and October 2021 to corroborate the quantitative data obtained by analysing aid repository data.

Results

The findings suggest that there was health aid displacement in Syria during key periods of crisis by a few key donors, such as the EU, Germany, Norway and Canada supporting responses to certain humanitarian crises. However, considering that the value of humanitarian aid is 50 times that of health aid, this displacement cannot be considered as critical. Also, there was insufficient evidence of health displacement across all donors.

The results also showed that the value of health aid as a proportion of aggregate health and humanitarian aid is only 2% in Syria, compared to 22% for the combined average of fragile states, which further indicates the predominance of humanitarian aid over health aid in the Syrian crisis context.

Conclusion

This study highlights that in very complex conflict-affected contexts such as Syria, it is difficult to suggest the use of health aid displacement as an effective tool for aid-effectiveness for donors as it does not reflect domestic needs and priorities. Yet there seems to be evidence of slight displacement for individual donors. However, we can suggest that donors vastly prefer to focus their investment in the humanitarian sector rather than the health sector in conflict-affected areas. There is an urgent need to increase donors’ focus on Syria’s health development aid and adopt the humanitarian-development-peace nexus to improve aid effectiveness that aligns with the increasing health needs of local communities, including IDPs, in this protracted conflict.
Long-term follow-up after discharge witnesses a slow decline of insulin autoantibodies in patients with insulin autoimmune syndrome complicated with Grave’s disease: a report of two cases
Authors: Zhao Lili , He Jinzhi , Ye Shandong , Chen Chao , Zhu Jie , Xiao Chunchun , Wu Tingni , Liu Zhicheng
Published: August 2023

Background

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization.

Case presentation

We report two patients with Grave’s disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge.

Conclusions

GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.
Current state of headache training within Canadian Neurology Residency program: a national survey
Authors: Perreault François , Christie Suzanne , Lelli Daniel , Humphrey- Murto Susan
Published: August 2023

Background

Headache disorders are the most common neurological disorders worldwide. Despite their widespread prevalence and importance, the topic of headache is inconsistently taught at both the undergraduate and postgraduate levels. The goal of this study is to establish a better picture of the current state of Headache Medicine (HM) training in Neurology postgraduate programs in Canada and describe the impact of the current pandemic on training in this domain.

Methods

Online surveys were sent to senior residents of adult Neurology programs in Canada. We also conducted telephone interviews with Neurology Program Directors. Descriptive statistics were analyzed, and thematic analysis was used to review free text.

Results

A total of 36 residents, and 3 Program Directors participated in the study. Most of the teaching in HM is done by headache specialists and general neurology faculty. Formal teaching is mainly given during academic half day. Most of the programs expose their residents to Onabotulinum toxin A injections and peripheral nerve blocks, but they don’t offer much formal teaching regarding these procedures. Residents consider HM teaching important and they would like to have more. They don’t feel comfortable performing interventional headache treatments, despite feeling this should be part of the skillset of a general neurologist.

Conclusion

Our study is the first to establish the current state of headache teaching in post-graduate neurology programs as perceived by trainees and program directors in Canada. The current educational offerings leave residents feeling poorly prepared to manage headaches, including procedural interventions. There is a need to diversify the source of teaching, so the educational burden doesn’t lie mostly upon Headache specialists who are already in short supply. Neurology Residency programs need to adapt their curriculum to face the current need in HM.
CCNB1 is a novel prognostic biomarker and promotes proliferation, migration and invasion in Wilms tumor
Authors: Xiang Bin , Chen Mei-Lin , Gao Zhi-Qiang , Mi Tao , Shi Qin-Lin , Dong Jun-Jun , Tian Xiao-Mao , Liu Feng , Wei Guang-Hui
Published: August 2023

Background

Wilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies.

Methods

High-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments.

Results

We initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with ‘cell cycle’, ‘DNA replication’. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients’ overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays.

Conclusion

Our study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target.
Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model
Authors: Kuang Meidan , Chen Yilin , Xing Yue , Du Min , Feng Huazhuo , Yang Qifeng , Wen Dongmei , Li Xuanyi , Yang Kai , Lin Ziying , Lai Ning , Jiang Qian , Liu Shiyun , Zhou Dansha , Hong Wei , Fu Xin , Lu Wenju , Zhao Tengteng , Wang Jian , Chen Yuqin
Published: August 2023

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.
Intravenous ferric carboxymaltose for iron repletion following acute heart failure in patients with and without diabetes: a subgroup analysis of the randomized AFFIRM-AHF trial
Authors: Rosano Giuseppe , Ponikowski Piotr , Vitale Cristiana , Anker Stefan D. , Butler Javed , Fabien Vincent , Filippatos Gerasimos , Kirwan Bridget-Anne , Macdougall Iain C. , Metra Marco , Ruschitzka Frank , Kumpeson Vasuki , Goehring Udo-Michael , van der Meer Peter , Jankowska Ewa A. ,   the AFFIRM-AHF investigators
Published: August 2023

Background

In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients.

Methods

Patients were stratified by diabetes yes/no at baseline. The effects of FCM vs placebo on primary (total HF hospitalizations and CV death) and secondary (total CV hospitalizations and CV death; CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalizations or CV death) endpoints at Week 52 and change vs baseline in disease-specific QoL (12-item Kansas City Cardiomyopathy Questionnaire [KCCQ-12]) at Week 24 were assessed by subgroup. For each endpoint, the interaction between diabetes status and treatment outcome was explored.

Results

Of 1108 AFFIRM-AHF patients, 475 (FCM: 231; placebo: 244) had diabetes and 633 (FCM: 327; placebo: 306) did not have diabetes. Patients with diabetes were more commonly male (61.5% vs 50.9%), with a higher frequency of ischemic HF etiology (57.9% vs 39.0%), prior HF history (77.7% vs 66.5%), and comorbidities (including previous myocardial infarction [49.3% vs 32.9%] and chronic kidney disease [51.4% vs 32.4%]) than those without diabetes. The annualized event rate/100 patient-years with FCM vs placebo for the primary endpoint was 66.9 vs 80.9 in patients with diabetes (rate ratio [RR]: 0.83, 95% CI 0.58–1.81) and 51.3 vs 66.9 in patients without diabetes (RR: 0.77, 95% CI 0.55–1.07), with no significant interaction between diabetes status and treatment effect (pinteraction = 0.76). Similar findings were observed for secondary outcomes. Change from baseline in KCCQ-12 overall summary score was numerically greater with FCM vs placebo at almost all time points in both subgroups, with no interaction between diabetes and treatment effect at Week 24.

Conclusions

The clinical and QoL benefits observed with intravenous FCM in patients with iron deficiency following stabilization from an AHF episode are independent of diabetes status.

Trial registration Clinicaltrials.gov, NCT02937454 (registered 10.18.2016).
Association between fingertip-measured advanced glycation end products and cardiovascular events in outpatients with cardiovascular disease
Authors: Hirai Tomoya , Fujiyoshi Kazuhiro , Yamada Satoru , Matsumoto Takuya , Kikuchi Junko , Ishida Kohki , Ishida Miwa , Shigeta Kyo , Tojo Taiki
Published: August 2023

Background

The accumulation of advanced glycation end products (AGEs) is associated with cardiovascular events in patients with cardiovascular disease (CVD). However, the relationship between the AGEs measured by an AGEs sensor noninvasively at the fingertip and prognosis in patients with CVD remains unclear. Therefore, this study aimed to determine the relationship between AGEs score and prognosis among patients with CVD.

Methods

A total of 191 outpatients with CVD were included. AGEs score were measured using an AGEs sensor and the patients were classified into groups by the median value of AGEs score. The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 30 months was compared between high- and low-AGEs score groups. In addition, receiver operating characteristic (ROC) curve analysis was used to calculate cutoff value for the AGEs score, which discriminates the occurrence of MACCE. Cox regression analysis was performed to identify the factors associated with the presence of MACCE. MACCE included cardiac death, myocardial infarction, percutaneous coronary intervention, heart failure, and stroke.

Results

AGEs score was normally distributed, with a median value of 0.51. No significant intergroup differences were found in laboratory findings, physical functions, or medications. The high-AGEs score group had a significantly higher incidence of MACCE than the low-AGEs score group (27.1 vs. 10.5%, P = 0.007). A high-AGEs score was a risk factor for MACCE (hazard ratio, 2.638; 95% confidence interval, 1.271–5.471; P = 0.009). After the adjustment for confounders other than 6-min walking distance, the AGEs score remained a factor associated with the occurrence of MACCE. The best cutoff AGEs score for the detection of MACCE was 0.51 (area under the curve, 0.642; P = 0.008; sensitivity, 72.2%; specificity, 54.8%).

Conclusions

AGEs score measured at the fingertip in patients with CVD is associated with MACCE. AGEs score, which can be measured noninvasively and easily, may be useful as an assessment for the secondary prevention of CVD in patients with CVD.
Heterologous production of the insecticidal pea seed albumin PA1 protein by Pichia pastoris and protein engineering to potentiate aphicidal activity via fusion to snowdrop lectin Galanthus nivalis agglutinin; GNA)
Authors: De-Thier Jake S. , Pyati Prashant , Bell Jack , Readshaw Jennifer J. , Brown Adrian P. , Fitches Elaine C.
Published: August 2023

Background

New bioinsecticides with novel modes of action are urgently needed to minimise the environmental and safety hazards associated with the use of synthetic chemical pesticides and to combat growing levels of pesticide resistance. The pea seed albumin PA1b knottin peptide is the only known proteinaceous inhibitor of insect vacuolar adenosine triphosphatase (V-ATPase) rotary proton pumps. Oral toxicity towards insect pests and an absence of activity towards mammals makes Pa1b an attractive candidate for development as a bioinsecticide. The purpose of this study was to investigate if Pichia pastoris could be used to express a functional PA1b peptide and if it’s insecticidal activity could be enhanced via engineering to produce a fusion protein comprising the pea albumin protein fused to the mannose-specific snowdrop lectin (Galanthus nivalis agglutinin; GNA).

Results

We report the production of a recombinant full-length pea albumin protein (designated PAF) and a fusion protein (PAF/GNA) comprised of PAF fused to the N-terminus of GNA in the yeast Pichia pastoris. PAF was orally toxic to pea (Acyrthosiphon pisum) and peach potato (Myzus persicae) aphids with respective, Day 5 LC50 values of 54 µM and 105 µM derived from dose–response assays. PAF/GNA was significantly more orally toxic as compared to PAF, with LC50 values tenfold (5 µM) and 3.3-fold (32 µM) lower for pea and peach potato aphids, respectively. By contrast, no phenotypic effects were observed for worker bumble bees (Bombus terristrus) fed PAF, GNA or PAF/GNA in acute toxicity assays. Confocal microscopy of pea aphid guts after pulse-chase feeding fluorescently labelled proteins provides evidence that enhanced efficacy of the fusion protein is attributable to localisation and retention of PAF/GNA to the gut epithelium. In contact assays the fusion protein was also found to be significantly more toxic towards A. pisum as compared to PAF, GNA or a combination of the two proteins.

Conclusions

Our results suggest that GNA mediated binding to V-type ATPase pumps acts to potentiate the oral and contact aphicidal activity of PAF. This work highlights potential for the future commercial development of plant protein-based bioinsecticides that offer enhanced target specificity as compared to chemical pesticides, and compatibility with integrated pest management strategies.