bluuebunny/crossref_metadata_2025 huggingface dataset:
C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease
Authors: Yao Qing , Long Chubing , Yi Pengcheng , Zhang Guangyong , Wan Wei , Rao Xiuqin , Ying Jun , Liang Weidong , Hua Fuzhou
Published: April 2024

Background

Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β‐amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.

Aims

Several studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.

Methods

A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case–control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.

Results

Overexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ‐secretase, apolipoprotein E4 (APOE4), acidic leucine‐rich nuclear phosphoprotein‐32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).

Discussion

The correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).

Conclusion

The overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.
Opioid use, prescribing and fatal overdose patterns among racial/ethnic minorities in the United States: A scoping review and conceptual risk environment model
Authors: Ezell Jerel M. , Pho Mai T. , Ajayi Babatunde P. , Simek Elinor , Shetty Netra , Goddard‐Eckrich Dawn A. , Bluthenthal Ricky N.
Published: April 2024

Issues

To date, there has been no synthesis of research addressing the scale and nuances of the opioid epidemic in racial/ethnic minority populations in the United States that considers the independent and joint impacts of dynamics such as structural disadvantage, provider bias, health literacy, cultural norms and various other risk factors.

Approach

Using the “risk environment” framework, we conducted a scoping review on PubMed, Embase and Google Scholar of peer‐reviewed literature and governmental reports published between January 2000 and February 2024 on the nature and scale of opioid use, opioid prescribing patterns, and fatal overdoses among racial/ethnic minorities in the United States, while also examining macro, meso and individual‐level risk factors.

Key Findings

Results from this review illuminate a growing, but fragmented, literature lacking standardisation in racial/ethnic classification and case reporting, specifically in regards to Indigenous and Asian subpopulations. This literature broadly illustrates racial/ethnic minorities' increasing nonmedical use of opioids, heightened burdens of fatal overdoses, specifically in relation to polydrug use and synthetic opioids, with notable elevations among Black/Latino subgroups, in addition uneven opioid prescribing patterns. Moreover, the literature implicates a variety of unique risk environments corresponding to dynamics such as residential segregation, provider bias, overpolicing, acculturative stress, patient distrust, and limited access to mental health care services and drug treatment resources, including medications for opioid use disorder.

Implications

There has been a lack of rigorous, targeted study on racial/ethnic minorities who use opioids, but evidence highlights burgeoning increases in usage, especially polydrug/synthetic opioid use, and disparities in prescriptions and fatal overdose risk‐phenomena tied to multi‐level forms of entrenched disenfranchisement.

Conclusion

There is a need for further research on the complex, overlapping risk environments of racial/ethnic minorities who use opioids, including deeper inclusion of Indigenous and Asian individuals, and efforts to generate greater methodological synergies in population classification and reporting guidelines.
Digital alcohol marketing and gender: A narrative synthesis
Authors: Lyons Antonia C. , Kersey Kate , Emslie Carol , Dimova Elena , Burrows Annamae
Published: April 2024

Issues

Alcohol marketing on social media platforms is pervasive and effective, reaching wide audiences and allowing interaction with users. We know little about the gendered nature of digital alcohol marketing, including how women and men are portrayed, how different genders respond and implications for gender relations. This review aimed to identify how males, females and other genders are targeted and represented in digital alcohol marketing, and how they are encouraged to engage with digital alcohol marketing content.

Approach

A narrative synthesis approach was employed. Academic literature and research reports were searched for studies on digital alcohol marketing published within the previous 10 years with a range of methods and designs. We reviewed the studies, extracted data relevant to gender and synthesised findings thematically.

Key Findings

The review included 17 articles and 7 reports with a range of designs and methods, including content analyses of digital material, interviews, focus groups and surveys. Our analysis identified three conceptual themes that captured many of the gendered results, namely: (i) leveraging a diversity of idealised femininities; (ii) amplifying hegemonic masculinity; and (iii) infiltrating everyday gendered life.

Implications and Conclusion

Alcohol marketing on social media is highly gendered and is designed to embed itself into everyday life in agile ways that reinforce traditional and evolving gendered stereotypes, activities, lifestyles and roles. Gendered engagement strategies are widely used to link alcohol to everyday gendered activities and identities to encourage alcohol purchase and consumption. This marketing normalises alcohol consumption and reproduces harmful gender norms and stereotypes.
Clinical features of quadricuspid aortic valve in middle‐aged and elderly patients: Insights from a regional study
Authors: Takiishi Azumi , Baba Yuichi , Ochi Yuri , Hotta Mizuki , Okazaki Nagisa , Yoshinaga Yuna , Miyamoto Shohei , Hirakawa Daigo , Kawaguchi Juri , Kubo Toru , Yamasaki Naohito , Tokuhiro Shinji , Kitaoka Hiroaki
Published: April 2024

Background

Quadricuspid aortic valve (QAV) is a rare congenital disease. The clinical characteristics of this disease remain unclear except for those in relatively young patients reported from tertiary referral hospitals. The aim of this study was to determine the clinical features of QAV in a regional population.

Methods and Results

We retrospectively investigated 25 340 consecutive patients over middle age (median age, 73 (IQR 65–80) years; range, 45–102 years) who underwent transthoracic echocardiography (TTE) at our institute during the period from April 2008 to December 2023. Eight (0.032%) of the patients (median age, 65 years; range, 47–91 years) were diagnosed with QAV. Six patients suffered from aortic regurgitation (AR), and one patient had mild aortic stenosis at the time of QAV diagnosis. Two patients who had severe AR at referral underwent aortic valve surgery. The severity of AR in the other patients was moderate or less. During a median follow‐up period of 27 months (range, 1–171 months), none of the patients other than above two patients had cardiac events. One patient died from a non‐cardiac cause at 94 years of age.

Conclusions

Patients diagnosed with QAV after middle age, who do not exhibit severe valve insufficiency at the time of diagnosis, may not experience worse clinical outcomes. However, further research is required for a better understanding of the long‐term outcomes.
Secondary‐tail formation during stolonization in the Japanese green syllid, Megasyllis nipponica
Authors: Sato Daisuke S. , Nakamura Mayuko , Teresa Aguado María , Miura Toru
Published: April 2024

Benthic annelids belonging to the family Syllidae show a distinctive sexual reproduction mode called “stolonization,” in which posterior segments are transformed into a reproductive individual‐like unit called a “stolon.” Megasyllis nipponica forms a stolon head and a secondary tail in the middle of the trunk before a stolon detaches, while, in the case of posterior amputation, posterior regeneration initiates at the wound after amputation. To understand the difference between posterior regeneration and secondary‐tail formation during stolonization, detailed comparisons between the developmental processes of these two tail‐formation types were performed in this study. Morphological and inner structural observations (i.e., cell proliferation and muscular/nervous development) showed that some processes of posterior regeneration, such as blastema formation and muscular/nervous regeneration at the amputation site, are missing during secondary‐tail formation. In contrast, the secondary tail showed some unique features, such as the formation of ventrolateral half‐tail buds that later fused in the middle and muscle/nerve branches formed before the detachment of the stolon. These novel features in the process of stolonization are suggested to be adaptive since the animals need to recover a posterior end quickly to stolonize again.
‘Like an imprisoned robin’: Similes by English language teachers on teaching in and beyond the times of COVID‐19
Authors: Dündar Esin
Published: April 2024

This qualitative study captured the reflections of 53 English language teachers from 40 different contexts including Bangladesh, Colombia, France, India, Scotland, Taiwan, Türkiye and the United Kingdom on teaching English during the times of COVID‐19 and its post‐effects on their practices. Data were collected through an online form consisting of three stems and the participants were asked to create similes about teaching English before, during and after the pandemic. By conducting thematic analysis, images created for each phase were categorized under occupational well‐being, digital transformation, transactional distance, gap of communication and social isolation. Teachers pointed out work overload, lack of administrational support, instructions' not making sense, decreasing level of participation, dropouts, loss of student–teacher interaction and isolation as the drawbacks of the process along with the possibility of digital transformation ahead of their profession.
Fix low dose venetoclax‐azacitidine treatment of unfit acute myeloid leukemia patients
Authors: Miklos Egyed , Oliver Tóth Peter , Adam Kellner , Eva Karadi , Balazs Kollar , Eszter Kovacs , Anett Pavlovics , Viktoria Gyori‐Korom , Jozsef Herczeg , Peter Rajnics
Published: April 2024

The prognosis of elderly AML patients had not even been improved by using hypomethylating agents; however, synergistic effect of combining azacitidin with venetoclax had resulted in a remarkable therapeutic advance. Our goal was to study the latter treatment with a new dosing regimen in a retrospective/observational study. In our department, we analyzed the data of AML patients who were unfit for curative high‐dose treatment and accepted the medication with a fixed‐dose of azacitidin and venetoclax combination (AZA‐VEN, 100 mg sc for 7 days—100 mg per os continuously). The primary end point was the overall survival. In total, 55 AML patients received the treatment between OCT/2019‐DEC/2022. Mean age was 69.4‐year (48–84), median overall survival was 17.2‐month (95% CI, 14.3–20.10) Composite CR: (CR + CRi) 62%. Side effect CTCAE 3 or higher: neutropenia with fever: 36.4%, anemia: 29.1%, thrombocytopenia: 16.4% and nausea 20%. AZA‐VEN combination treatment of our unfit AML patients was found to be a good therapeutic option. The results achieved with significantly lower doses of the fixed dose of AZA‐VEN are comparable to the conclusions of the VIALE‐A study, and the less severe side effects we have observed are explained by the milder neutropenia of the newly introduced regimen.
CAR‐T from cord blood in a patient with Ph+ acute lymphoblastic leukemia relapsing after hematopoietic stem cell transplantation
Authors: Marra John Donald , Galli Eugenio , Giammarco Sabrina , Metafuni Elisabetta , Minnella Gessica , Fosso Federica , Marietti Sara , Sica Simona , Sorà Federica , Chiusolo Patrizia
Published: April 2024

While there is intense interest in the production of allogeneic CAR‐T cells from umbilical cord units, little is known about the reactivity and persistence of CAR‐T cells of umbilical origin. We report the case of a patient at our hematological center with multiple relapsing Ph+ B‐ALL, notably a Blinatunomab non‐responder, who underwent therapy with Brexucabtagene Autoleucel following relapse on Ponatinib post‐allogeneic hematopoietic stem cell transplantation. The patient achieved a rapid CAR‐T expansion and durable remission presenting in good clinical conditions 6 months post‐CAR‐T infusion, without manifestations of graft‐versus‐host disease. The case report provides insight into the reactivity and persistence of CAR‐T cells of umbilical origin, confirming the potential promise of allogeneic umbilical cord‐derived CAR‐T cells.
Naloxone increases conditioned fear responses during social buffering in male rats
Authors: Yamasaki Takumi , Kiyokawa Yasushi , Munetomo Arisa , Takeuchi Yukari
Published: April 2024

Social buffering is the phenomenon in which the presence of an affiliative conspecific mitigates stress responses. We previously demonstrated that social buffering completely ameliorates conditioned fear responses in rats. However, the neuromodulators involved in social buffering are poorly understood. Given that opioids, dopamine, oxytocin and vasopressin play an important role in affiliative behaviour, here, we assessed the effects of the most well‐known antagonists, naloxone (opioid receptor antagonist), haloperidol (dopamine D2 receptor antagonist), atosiban (oxytocin receptor antagonist) and SR49059 (vasopressin V1a receptor antagonist), on social buffering. In Experiment 1, fear‐conditioned male subjects were intraperitoneally administered one of the four antagonists 25 min prior to exposure to a conditioned stimulus with an unfamiliar non‐conditioned rat. Naloxone, but not the other three antagonists, increased freezing and decreased walking and investigation as compared with saline administration. In Experiment 2, identical naloxone administration did not affect locomotor activity, anxiety‐like behaviour or freezing in an open‐field test. In Experiment 3, after confirming that the same naloxone administration again increased conditioned fear responses, as done in Experiment 1, we measured Fos expression in 16 brain regions. Compared with saline, naloxone increased Fos expression in the paraventricular nucleus of the hypothalamus and decreased Fos expression in the nucleus accumbens shell, anterior cingulate cortex and insular cortex and tended to decrease Fos expression in the nucleus accumbens core. Based on these results, we suggest that naloxone blocks social buffering of conditioned fear responses in male rats.
Inhibition of 14‐3‐3 proteins increases the intrinsic excitability of mouse hippocampal CA1 pyramidal neurons
Authors: Logue Jordan B. , Vilmont Violet , Zhang Jiajing , Wu Yuying , Zhou Yi
Published: April 2024

14‐3‐3 proteins are a family of regulatory proteins that are abundantly expressed in the brain and enriched at the synapse. Dysfunctions of these proteins have been linked to neurodevelopmental and neuropsychiatric disorders. Our group has previously shown that functional inhibition of these proteins by a peptide inhibitor, difopein, in the mouse brain causes behavioural alterations and synaptic plasticity impairment in the hippocampus. Recently, we found an increased cFOS expression in difopein‐expressing dorsal CA1 pyramidal neurons, indicating enhanced neuronal activity by 14‐3‐3 inhibition in these cells. In this study, we used slice electrophysiology to determine the effects of 14‐3‐3 inhibition on the intrinsic excitability of CA1 pyramidal neurons from a transgenic 14‐3‐3 functional knockout (FKO) mouse line. Our data demonstrate an increase in intrinsic excitability associated with 14‐3‐3 inhibition, as well as reveal action potential firing pattern shifts after novelty‐induced hyperlocomotion in the 14‐3‐3 FKO mice. These results provide novel information on the role 14‐3‐3 proteins play in regulating intrinsic and activity‐dependent neuronal excitability in the hippocampus.
Dissecting the role of mitogen‐activated protein kinase Hog1 in yeast flocculation
Authors: Kumawat Ramesh , Tomar Raghuvir Singh
Published: April 2024

Living organisms are frequently exposed to multiple biotic and abiotic stress forms during their lifetime. Organisms cope with stress conditions by regulating their gene expression programs. In response to different environmental stress conditions, yeast cells activate different tolerance mechanisms, many of which share common signaling pathways. Flocculation is one of the key mechanisms underlying yeast survival under unfavorable environmental conditions, and the Tup1‐Cyc8 corepressor complex is a major regulator of this process. Additionally, yeast cells can utilize different mitogen‐activated protein kinase (MAPK) pathways to modulate gene expression during stress conditions. Here, we show that the high osmolarity glycerol (HOG) MAPK pathway is involved in the regulation of yeast flocculation. We observed that the HOG MAPK pathway was constitutively activated in flocculating cells, and found that the interaction between phosphorylated Hog1 and the FLO genes promoter region increased significantly upon sodium chloride exposure. We found that treatment of cells with cantharidin decreased Hog1 phosphorylation, causing a sharp reduction in the expression of FLO genes and the flocculation phenotype. Similarly, deletion of HOG1 in yeast cells reduced flocculation. Altogether, our results suggest a role for HOG MAPK signaling in the regulation of FLO genes and yeast flocculation.
Do corporate site visits affect the informational role of independent directors?
Authors: Wang Qiong , Cao Zhangfan , Lee Edward
Published: April 2024

This study examines the influence of corporate site visits on information acquisition and dissemination by independent directors (IDs). Employing two unique sources of data from Chinese listed firms based on the mandatory disclosure of IDs’ (i) site visit activities and (ii) opinions about corporate decisions, we find that the acquisition of firm‐specific information and the dissemination of such information to the market are greater among IDs who conduct visits than their counterparts without such visits. Moreover, this effect is more pronounced in firms with complex information environments, in firms with lower proprietary costs, and among IDs with greater internal information asymmetry, superior external information, and stronger incentives and abilities to perform their duties. Furthermore, the firm‐specific information disseminated by IDs leads to stronger market reactions and improves stock price efficiency. Our study shows that site visits contribute to the informational role of IDs, and our evidence offers important corporate governance and regulatory implications.
Testing the deep‐sea glacial disturbance hypothesis as a cause of low, present‐day Norwegian Sea diversity and resulting steep latitudinal diversity gradient, using fossil records
Authors: Jöst Anna B. , Huang Huai‐Hsuan M. , Hong Yuanyuan , Wei Chih‐Lin , Bauch Henning A. , Thibodeau Benoit , Cronin Thomas M. , Okahashi Hisayo , Yasuhara Moriaki
Published: April 2024

Aim

Within the intensively‐studied, well‐documented latitudinal diversity gradient, the deep‐sea biodiversity of the present‐day Norwegian Sea stands out with its notably low diversity, constituting a steep latitudinal diversity gradient in the North Atlantic. The reason behind this has long been a topic of debate and speculation. Most prominently, it is explained by the deep‐sea glacial disturbance hypothesis, which states that harsh environmental glacial conditions negatively impacted Norwegian Sea diversities, which have not yet fully recovered. Our aim is to empirically test this hypothesis. Specific research questions are: (1) Has deep‐sea biodiversity been lower during glacials than during interglacials? (2) Was there any faunal shift at the Mid‐Brunhes Event (MBE) when the mode of glacial–interglacial climatic change was altered?

Location

Norwegian Sea, deep sea (1819–2800 m), coring sites MD992277, PS1243, and M23352.

Time period

620.7–1.4 ka (Middle Pleistocene–Late Holocene).

Taxa studied

Ostracoda (Crustacea).

Methods

We empirically test the deep‐sea glacial disturbance hypothesis by investigating whether diversity in glacial periods is consistently lower than diversity in interglacial periods. Additionally, we apply comparative analyses to determine a potential faunal shift at the MBE, a Pleistocene event describing a fundamental shift in global climate.

Results

The deep Norwegian Sea diversity was not lower during glacial periods compared to interglacial periods. Holocene diversity was exceedingly lower than that of the last glacial period. Faunal composition changed substantially between pre‐ and post‐MBE.

Main conclusions

These results reject the glacial disturbance hypothesis, since the low glacial diversity is the important precondition here. The present‐day‐style deep Norwegian Sea ecosystem was established by the MBE, more specifically by MBE‐induced changes in global climate, which has led to more dynamic post‐MBE conditions. In a broader context, this implies that the MBE has played an important role in the establishment of the modern polar deep‐sea ecosystem and biodiversity in general.
Impaired oral status is associated with sarcopenic obesity in post‐stroke patients
Authors: Shiraishi Ai , Yoshimura Yoshihiro , Wakabayashi Hidetaka , Nagano Fumihiko , Matsumoto Ayaka , Shimazu Sayuri , Kido Yoshifumi , Bise Takahiro , Kuzuhara Aomi , Hori Kota , Hamada Takenori , Yoneda Kouki , Maekawa Kenichiro
Published: April 2024

Purpose

Oral problems and muscle health are indeed significant concerns in ageing populations. However, there is limited evidence concerning the association between these issues. The study's focus was to investigate the association between oral problems and sarcopenic obesity, wherein sarcopenia and obesity coexist concurrently, in post‐stroke patients.

Methods

This retrospective, observational, cross‐sectional study included patients hospitalised for post‐stroke rehabilitation. Oral problems were assessed using the Revised Oral Assessment Guide (ROAG). Sarcopenic obesity was diagnosed according to the European Society of Clinical Nutrition and Metabolism/European Association for the Study of Obesity criteria. Multiple linear regression analysis was used to examine the association between the ROAG and sarcopenic obesity after adjusting for confounding factors.

Results

A total of 760 patients were included, with a mean (SD) age of 71 (9) years, of whom 408 (54.7%) were male. The median (interquartile range, 25th and 75th percentiles) ROAG was 11 [9, 13]. Sarcopenic obesity was diagnosed in 16 (3.9%) men, 18 (5.1%) women, and 34 (4.5%) patients overall. Multivariate linear analysis showed that ROAG was significantly and positively associated with sarcopenic obesity (β = .091, P = .023), followed by obesity alone (β = .084, P = .044), and sarcopenia alone (β = .081, P = .037).

Conclusion

Oral problems were associated with sarcopenic obesity in post‐stroke. Oral assessment and intervention may have a positive impact on ADL and QOL in post‐stroke patients with sarcopenic obesity.
The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis
Authors: Kirkland Scott W. , Visser Lloyd , Meyer Jillian , Junqueira Daniela R. , Campbell Sandra , Villa‐Roel Cristina , Friedman Benjamin W. , Essel Nana Owusu , Rowe Brian H.
Published: April 2024

Objectives

To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine.

Background

Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear.

Methods

Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk‐of‐bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096).

Results

A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference −3.36, 95% confidence interval [CI] −4.64 to −2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74–4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12–3.60; metoclopramide RR 2.58, 95% CI 1.90–3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61–6.49; metoclopramide RR 4.1, 95% CI 3.02–5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics.

Conclusions

Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first‐line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision‐making model be considered to effectively identify the best treatment option based on the patient's needs.
Challenges in the management of new daily persistent headache at a tertiary headache center—A retrospective real‐world evidence study
Authors: Linnet Thor , Hussein Marwa , Schytz Henrik Winther , Bendtsen Lars , Amin Faisal Mohammad
Published: April 2024

Objective

In this retrospective cross‐sectional real‐world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to identify potential pharmacological agents for the treatment of new daily persistent headache (NDPH).

Background

NDPH is an enigmatic headache disorder with abrupt onset and chronic duration for which evidence‐based treatments are lacking. NDPH is a diagnosis of exclusion, for which secondary headaches must be ruled out and the etiology remains idiopathic. The sparse investigations of this disorder have not yielded a pathophysiological basis and no effective treatment for NDPH has been found.

Methods

All patients with an NDPH diagnosis at the DHC were enrolled (n = 64). First, we reviewed the records of all patients with an NDPH diagnosis to evaluate whether they fulfilled the diagnostic criteria. Next, we extracted all the trialled acute and prophylactic pharmacological interventions for the included patients. Then, pharmacological interventions that had been tried in ≥ 20 patients were analyzed post hoc with efficacy as the outcome, which was stratified in five effect categories (“no effect,” “partial effect,” “full effect,” “partial effect and cessation due to adverse events,” and “full effect and cessation due to adverse events”). Descriptive statistical analysis was performed, and the results were schematically presented (see Table 2).

Results

Fifty‐one patients out of 64 were found to fulfill NDPH criteria and were included in the study. The drugs tried by ≥ 20 patients were amitriptyline (n = 34), candesartan (n = 27), and mirtazapine (n = 20). No patients experienced a complete effect with these drugs while 9% (3/34), 26% (7/27), and 15% (3/20) experienced a partial effect with no adverse events that led to treatment discontinuation, respectively. The remaining patients experienced either no effect or a partial effect with adverse events leading to treatment discontinuation.

Conclusion

In this study we add real‐world evidence to suggest that prophylactic drugs conventionally used for treating chronic migraine and chronic tension‐type headache have limited utility for treating NDPH; however, a partial response in 26% of patients using candesartan and 15% of patients using mirtazapine warrants further investigation in randomized double‐blinded placebo‐controlled trials.
Real‐world use of long‐acting cabotegravir and rilpivirine: 12‐month results of the inJectable Antiretroviral therapy feasiBility Study (JABS)
Authors: John M. , Williams L. , Nolan G. , Bonnett M. , Castley A. , Nolan D.
Published: April 2024

Objectives

The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long‐acting regimens in a ‘real world’ Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non‐adherence.

Methods

JABS was a 12‐month, single‐centre, single‐arm, open‐label phase IV study of long‐acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV‐1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14‐day dosing window over 12 months, out of the total prescribed doses. Secondary endpoints included proportions of missed appointments, use of oral bridging, discontinuations, virological failures, adverse events and participant‐reported outcomes. A multidisciplinary adherence programme embedded in the clinical service known as REACH provided support to JABS participants.

Results

Of 60 participants enrolled by May 2022, 60% had one or more complexity or vulnerability factors identified, including absence of social supports (50%), mental health issues, alcohol or drug use (30%) and financial hardship or instability (13%), among others. Twenty‐seven per cent of participants had historical non‐adherence to antiretroviral therapy. Out of 395 prescribed doses, 97.2% of injections were administered within correct dosing windows at clinic visits. Two courses of short‐term oral bridging were required. The rate of injection site reactions was 29%, the majority being grade 1–2. There were no virological failures, no serious adverse events and only one injection‐related study discontinuation. High baseline treatment satisfaction and acceptability of injections increased by month 12. Those with vulnerability factors had similar adherence to injections as those without such factors. Ninety‐eight per cent of the participants who completed 12 months on the study have maintained long‐acting therapy, virological suppression and retention in care.

Conclusions

Long‐acting cabotegravir plus rilpivirine was associated with very high adherence, maintenance of virological suppression, safety and treatment satisfaction in a diverse Australian clinic population, comparable to results of phase III randomized clinical trials. Individuals with vulnerability factors can achieve adherence to injections with individualized support. Long‐acting therapies in this group can increase the subsequent engagement in clinical care.
Recent advances in rapid and reliable biosensors for detection of porcine gelatine
Authors: Sari Rizki Muharami Cedia , Wyantuti Santhy , Zein Muhammad Ihda H.L. , Rahimah Souvia , Irkham Irkham , Ibrahim Abdullahi Umar , Ozsoz Mehmet , Hartati Yeni Wahyuni
Published: April 2024

Gelatine is obtained from the hydrolysis of collagen in bones, skin, fins, fish scales and insect bodies of cattle, pigs, camels, poultry, fish and insects. Consequently, the diversity and availability of gelatine sources, along with gelatine authentication, are concerns for those consuming gelatine products from religious, health and economic perspectives. Therefore, rapid and reliable protein‐ or DNA‐based detection methods have been developed for gelatine authentication. This review discusses and evaluates biosensor methods, comparing them with various analytical methods in terms of their popularity and precision. Additionally, the development of biosensor methods has been explored to identify a reference for a rapid, accurate, portable and simple method for gelatine detection with a low detection limit and high specificity.
Development of a yeast‐free bread using legume and nut flours in a gluten‐free flour: Techno‐functional characteristics and sensory evaluation
Authors: Tuna Ayca , Ortiz‐Solà Jordi , López‐Mas Laura , Baser Filiz , Kallas Zein , Aguiló‐Aguayo Ingrid , Gulec Sukru , Ozen Banu , Tokatli Figen
Published: April 2024

This study aimed to investigate the effect of combined use of legume and nut flours on physical, nutritional and sensory properties of yeast‐free bread by substituting gluten‐free flour with hazelnut and white bean flours. Yeast‐free bread containing a mixture of 30% hazelnut and white bean flours was found to have the lowest hardness (9.04 N) and the largest specific volume (1.51 mL g−1) compared to the reference gluten‐free bread (18 N and 1.43 mL g−1) using a mixture design. Hazelnut and bean flours improved the in vitro starch digestion, reducing rapidly digestible starch by 29% and increasing resistant starch compared to the reference bread. Free choice profiling sensory analysis revealed that the developed breads containing nuts and legumes differed from the standard gluten‐free formulation and a commercial product available on the market. The combined use of bean and hazelnut flours was demonstrated as functional ingredients for enhancement of nutritional, sensory and textural aspects.
60Co γ‐radiation at low‐dose level alters volatile compounds of blueberry during storage
Authors: Liu Dongjie , Liu Zhen , Lan Bifeng , Ma Lukai , Huang Hua , Xiao Gengsheng , Wang Qin , Wang Feng
Published: April 2024

60Co γ‐radiation was applied to blueberry fruits in an effort to investigate a safe, eco‐friendly and effective blueberry preservation technique. However, the preservation effects were variable depending on tissue tolerance to irradiation doses. Moreover, irradiation may cause off‐odour. In this study, we examined the effects of three low doses of 60Co γ‐radiation on the physical and flavour attributes of blueberry. The results showed that 60Co γ‐radiation did not significantly improve fruit quality but extend the shelf life up to 15 days at 25 °C and 30 days at 4 °C. Compared with the control group, the preservation effect of 0.5–1.0 kGy irradiation treatment on blueberry fruit was not obvious before 15 days but maintained 65% of fruit firmness and reduced the loss of nutrients afterwards at 4 °C. At 25 °C, irradiation treatment caused up to a 150% increase in polyphenol oxidase activity, which was relevant to colour changes in late storage. Headspace Gas Chromatography Ion Mobility Spectrometry (HS‐GC‐IMS) was applied, and 33 volatile organic compounds (VOCs) in blueberry treated with different radiation doses were identified, including 11 esters, 8 aldehydes, 7 alcohols, 6 ketones and other substances, which increased with increasing radiation dose. Radiation reduced the green taste of blueberry and promoted their ripening. Radiation above the level of 1.02 kGy led to the flavour deterioration of blueberry such as ethyl trans‐2‐butenoate. The side effects of radiation on the aroma of blueberry could be offset by low‐temperature storage. Blueberry stored at 4 °C contained more aldehydes with a heavier fresh/green aroma. Six aromas were proposed to be characteristic odour markers of radiated blueberry.
New method to differentiate between lupus anticoagulants, progressive coagulation inhibitors and coagulation factor deficiencies in the mixing tests
Authors: Shimomura Daiki , Kumano Osamu , Ueda Kaori , Kitano Keisuke , Arai Nobuo , Shimada Masashi , Kamioka Mikio
Published: April 2024

Introduction

Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation.

Methods

Twenty‐six LA‐positive, 8 progressive coagulation factor VIII inhibitor, and 35 coagulation deficient samples were employed. APTT were measured for normal plasma, patient plasma, and mixing plasma prepared at a ratio of 1:1 proportion in both without incubation and 2 h‐incubation. New two parameters named as ALD50 and mixture plasma—patient plasma after Warming change rate Subtraction (WaS) calculated from the clotting times of normal, 1:1 mixing and patient samples with/without 2 h‐incubation were established. In the samples with WaS result of <10.2%, ALD50 of ≥87.8%, and < 87.8% were defined as LA and coagulation factor deficiency, respectively, and WaS of ≥10.2% defined progressive coagulation factor inhibitors.

Results

Sensitivity and specificity to LA were 80.8% and 93.0% for ALD50, and sensitivity and specificity to progressive coagulation factor inhibitor were 100.0% and 100.0% for WaS, respectively. The agreement between sample classification and WaS‐ALD50 was 88.4% (61/69).

Conclusions

ALD50 and WaS showed acceptable sensitivity and specificity to LA and progressive coagulation factor inhibitor, respectively. These indexes would be useful for the differentiation between LA, factor deficiency, and progressive coagulation factor inhibitor in the mixing tests.
Bricker versus Wallace ureteroileal anastomosis: A multi‐institutional propensity score‐matched analysis
Authors: Al‐Nader Mulham , Krafft Ulrich , Hess Jochen , Kesch Claudia , AbdelRazek Mostafa , Abolyosr Ahmad , Alsagheer Gamal A. , Mohamed Omar , Fathi Atef , Tschirdewahn Stephan , Hadaschik Boris A. , Mahmoud Osama
Published: April 2024

Aim of the study

The aim of our study is to evaluate the difference in stricture rate between matched groups of Bricker and Wallace techniques for ureteroileal anastomosis.

Patients and methods

A retrospective analysis of patients undergoing urinary diversion (UD) with Bricker and Wallace ureteroileal anastomosis at two university hospitals. Two groups of Bricker and Wallace patients were matched in a 1:1 ratio based on the age, sex, body mass index (BMI), Charlson comorbidity index (CCI), preoperative hydronephrosis, prior radiation therapy or abdominal surgery, pathologic T and N stages and 30‐days‐Clavien grade complications≥III. A multivariable Cox regression analysis was conducted to identify predictors of ureteroenteric stricture (UES) in all patients.

Results

Overall, 740 patients met the inclusion criteria and 209 patients in each group were propensity matched. At a similar median follow‐up of 25 months, UES was detected in 25 (12%) and 30 (14.4%) patients in Bricker and Wallace groups, respectively (p = 0.56). However, only one patient in the Bricker group developed a bilateral stricture compared to 15 patients in the Wallace group, resulting in a significantly higher number of affected renal units in the Wallace group: 45 (10.7%) versus only 26 (6.2%) in the Bricker group (p = 0.00). On multivariable extended Cox analysis, prior radiotherapy, presence of T4 pelvic malignancy and nodal positive disease were independent predictor of UES formation.

Conclusion

The technique of ureteroileal anastomosis itself does not increase the rate of stricture; however, conversion of two renal units into one is associated with a higher incidence of bilateral upper tract involvement.
Modulation of intestinal epithelial permeability by chronic small intestinal helminth infections
Authors: Mules Thomas C , Tang Jeffry S , Vacca Francesco , Yumnam Bibek , Schmidt Alfonso , Lavender Brittany , Maclean Kate , Noble Sophia‐Louise , Waugh Craig , van Ginkel Roel , Camberis Mali , Le Gros Graham , Inns Stephen
Published: April 2024

Increased permeability of the intestinal epithelial layer is linked to the pathogenesis and perpetuation of a wide range of intestinal and extra‐intestinal diseases. Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed as a treatment for many of the same diseases. Helminths induce immunoregulatory changes in their host which could decrease epithelial permeability, which is highlighted as a potential mechanism through which helminths treat disease. Despite this, the influence of a chronic helminth infection on epithelial permeability remains unclear. This study uses the chronically infecting intestinal helminth Heligmosomoides polygyrus to reveal alterations in the expression of intestinal tight junction proteins and epithelial permeability during the infection course. In the acute infection phase (1 week postinfection), an increase in intestinal epithelial permeability is observed. Consistent with this finding, jejunal claudin‐2 is upregulated and tricellulin is downregulated. By contrast, in the chronic infection phase (6 weeks postinfection), colonic claudin‐1 is upregulated and epithelial permeability decreases. Importantly, this study also investigates changes in epithelial permeability in a small human cohort experimentally challenged with the human hookworm, Necator americanus. It demonstrates a trend toward small intestinal permeability increasing in the acute infection phase (8 weeks postinfection), and colonic and whole gut permeability decreasing in the chronic infection phase (24 weeks postinfection), suggesting a conserved epithelial response between humans and mice. In summary, our findings demonstrate dynamic changes in epithelial permeability during a chronic helminth infection and provide another plausible mechanism by which chronic helminth infections could be utilized to treat disease.
Relative Effectiveness of the MF59®‐Adjuvanted Influenza Vaccine Versus High‐Dose and Non‐Adjuvanted Influenza Vaccines in Preventing Cardiorespiratory Hospitalizations During the 2019–2020 US Influenza Season
Authors: Imran Mahrukh , Puig‐Barbera Joan , Ortiz Justin R. , Lopez‐Gonzalez Lorena , Dean Alex , Bonafede Machaon , Haag Mendel D. M.
Published: April 2024

Background

Adults ≥ 65 years of age have suboptimal influenza vaccination responses compared to younger adults due to age‐related immunosenescence. Two vaccines were specifically developed to enhance protection: MF59‐adjuvanted trivalent influenza vaccine (aIIV3) and high‐dose egg‐based trivalent influenza vaccine (HD‐IIV3e).

Methods

In a retrospective cohort study conducted using US electronic medical records linked to claims data during the 2019–2020 influenza season, we compared the relative vaccine effectiveness (rVE) of aIIV3 with HD‐IIV3e and a standard‐dose non‐adjuvanted egg‐based quadrivalent inactivated influenza vaccine (IIV4e) for the prevention of cardiorespiratory hospitalizations, including influenza hospitalizations. We evaluated outcomes in the “any” diagnosis position and the “admitting” position on the claim. A doubly robust methodology using inverse probability of treatment weighting and logistic regression was used to adjust for covariate imbalance. rVE was calculated as 100 * (1 − ORadjusted).

Results

The study included 4,299,594 adults ≥ 65 years of age who received aIIV3, HD‐IIV3e, or IIV4e. Overall, aIIV3 was associated with lower proportions of cardiorespiratory hospitalizations with diagnoses in any position compared to HD‐IIV3e (rVE = 3.9% [95% CI, 2.7–5.0]) or IIV4e (9.0% [95% CI, 7.7–10.4]). Specifically, aIIV3 was more effective compared with HD‐IIV3e and IIV4e in preventing influenza hospitalizations (HD‐IIV3e: 9.7% [95% CI, 1.9–17.0]; IIV4e: 25.3% [95% CI, 17.7–32.2]). Consistent trends were observed for admitting diagnoses.

Conclusion

Relative to both HD‐IIV3e and IIV4e, aIIV3 provided improved protection from cardiorespiratory or influenza hospitalizations.
How many blood pressure measurements should we take in the office?
Authors: Özkan Gülsüm , Ulusoy Şükrü , Yılmaz Rahmi , Değer Serpil Müge , Derici Ülver , Arınsoy Turgay , Erdem Yunus ,   Turkish Society of Hypertension and Renal Diseases
Published: April 2024

No consensus has emerged among different guidelines concerning how many blood pressure (BP) measurements should be performed at office visits in the diagnosis of hypertension. The purpose of this study was to examine the compatibility of various multiple average office BP measurements and 24‐h BP monitoring (ABPM) in patients followed up in the posthoc analysis of the Cappadocia hypertension cohort. A total 1158 office BP measurements by 207 patients were examined. The results were then classified as G1 (average of the 1st and 2nd BP), G2 (average of the 2nd and 3rd), G3 (average of the 2nd, 3rd, and 4th), G4 (average of the 2nd, 3rd, 4th, and 5th), and G5 (average of all five measurements). Compatibility between the average values in the groups and concomitant 24‐h ABPM data was examined. While a significant difference was observed between daytime 24‐h ABPM SBP and G1 (p = .002), no difference was found in the other groups. Office DBP approached the daytime 24‐h ABPM values as the number of measurements in the five groups increased, although average office DBP data in all groups were higher than daytime 24‐h ABPM DBP (p = .000 for all). In light of our study results, we recommend that three office BP measurements be performed and that the average of the 2nd and 3rd measurements be used for SBP, while in terms of DBP, we recommend that as many measurements as possible be taken without the 1st value being included in the average.