bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory protein interactions in Dehalobacter sp. strain 8M revealed through genomic and native proteomic analyses
Authors: Soder‐Walz Jesica M. , Wasmund Kenneth , Deobald Darja , Vicent Teresa , Adrian Lorenz , Marco‐Urrea Ernest
Published: July 2023

Dehalobacter (Firmicutes) encompass obligate organohalide‐respiring bacteria used for bioremediation of groundwater contaminated with halogenated organics. Various aspects of their biochemistry remain unknown, including the identities and interactions of respiratory proteins. Here, we sequenced the genome of Dehalobacter sp. strain 8M and analysed its protein expression. Strain 8M encodes 22 reductive dehalogenase homologous (RdhA) proteins. RdhA D8M_v2_40029 (TmrA) was among the two most abundant proteins during growth with trichloromethane and 1,1,2‐trichloroethane. To examine interactions of respiratory proteins, we used blue native gel electrophoresis together with dehalogenation activity tests and mass spectrometry. The highest activities were found in gel slices with the highest abundance of TmrA. Protein distributions across gel lanes provided biochemical evidence that the large and small subunits of the membrane‐bound [NiFe] uptake hydrogenase (HupL and HupS) interacted strongly and that HupL/S interacted weakly with RdhA. Moreover, the interaction of RdhB and membrane‐bound b‐type cytochrome HupC was detected. RdhC proteins, often encoded in rdh operons but without described function, migrated in a protein complex not associated with HupL/S or RdhA. This study provides the first biochemical evidence of respiratory protein interactions in Dehalobacter, discusses implications for the respiratory architecture and advances the molecular comprehension of this unique respiratory chain.
Elected or Selected? The Continuing Constitutional Conundrum of House of Lords Reform
Authors: Dorey Peter
Published: July 2023

The 1911 Parliament Act decreed that Lords reform was ‘an urgent question which brooks no delay’, yet the subsequent 112 years have witnessed only sporadic and inchoate reforms. The issue has invariably suffered both from interparty disagreement between the Conservatives and Labour and, more importantly, intraparty disagreements owing to the divergent views and irreconcilable disagreements among Labour MPs over ‘what is to be done?’, and recognition that any reform which enhanced the legitimacy of the second chamber would threaten the pre‐eminence of the House of Commons and a Labour government therein.

A similar fate is likely to befall the Labour Party's latest proposal for replacing the current House of Lords with an elected second chamber. Meanwhile, the Conservative peer, Lord Norton, is seeking to place the House of Lords Appointments Commission (HOLAC) on a statutory basis and impose stricter criteria on prime ministerial nominations for peerages. Yet, this would still leave any Prime Minister with considerable powers of patronage in appointing members of the second chamber. This article therefore suggests that a Prime Minister should only be permitted to nominate 20 per cent of the membership, with the rest appointed via HOLAC itself, thereby depoliticising the process as far as practicably possible, and imbuing it with greater public trust.
Understanding Veterans' intimate partner violence use and patterns of healthcare utilization
Authors: Relyea Mark R. , Presseau Candice , Runels Tessa , Humbert Michelle M. , Martino Steve , Brandt Cynthia A. , Haskell Sally G. , Portnoy Galina A.
Published: July 2023

Objective

To understand the association between Veterans' healthcare utilization and intimate partner violence (IPV) use (i.e., perpetration) in order to (1) identify conditions comorbid with IPV use and (2) inform clinical settings to target for IPV use screening, intervention, and provider training.

Data Sources and Study Setting

We examined survey data from a national sample of 834 Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) Veterans.

Study Design

We assessed associations between past‐year IPV use and medical treatment, health issues, and use of Veterans Health Administration (VA) and non‐VA services using chi‐square tests and logistic regression.

Data Collection/Extraction Methods

Data were derived from the Department of Defense OEF/OIF/OND Roster. Surveys were sent to all women Veterans and a random sample of men from participating study sites.

Principal Findings

Half (49%) of the Veterans who reported utilizing VA healthcare in the past year indicated using IPV. Q values using a 5% false discovery rate indicated that Veterans who used IPV were more likely than Veterans who did not use IPV to have received treatment for post‐traumatic stress disorder (PTSD; 39% vs. 27%), chronic sleep problems (36% vs. 26%), anxiety or depression (44% vs. 36%), severe chronic pain (31% vs. 22%), and stomach or digestive disorders (24% vs. 16%). Veterans who used IPV were also more likely than Veterans who did not use IPV to have received medical treatment in the past year (86% vs. 80%), seen psychiatrists outside VA (39% vs. 20%), and have outpatient healthcare outside VA (49% vs. 41%). IPV use was not related to whether Veterans received care from VA or non‐VA providers.

Conclusions

Veterans' IPV use was related to greater utilization of services for mental health, chronic pain, and digestive issues. Future research should examine whether these are risk factors or consequences of IPV use.
A novel method for sorting and reassociating commingled human remains using deviation analysis
Authors: Litavec Helen
Published: July 2023

This study provides an innovative and novel method for sorting commingled human remains at the sacroiliac joint using deviation analyses. Virtual models were created at the University of Tennessee‐Knoxville Donated Skeletal Collection from 69 os coxae and 66 sacra using an EinScan‐Pro 2× + Handheld Surface Scanner. The shape of the auricular surfaces was analyzed in Geomagic Wrap 2017, and the congruency of the two auricular surfaces was measured using a deviation analysis. ROC curves were performed on a reference sample composed of 200 commingled and non‐commingled joint pairs to identify threshold values that could help sort the commingled remains. A validation sample of 225 pairs was subsequently analyzed to demonstrate the efficacy of this new method on a sample of unknown individuals. Statistical analyses demonstrated that the deviation analysis values from sacroiliac joints of commingled pairs were significantly larger than those from non‐commingled individuals (p < 0.0001). Based on the selected threshold values, 98%–100% of pairs were correctly sorted and reassociated. This novel and objective technique improves upon previously subjective strategies for sorting commingled remains and, in the future, will be applied to additional joint surfaces.
Management practices and productivity: Does employee representation play a moderating role?
Authors: Jirjahn Uwe , Laible Marie‐Christine , Mohrenweiser Jens
Published: July 2023

Bloom and Van Reenen (2007) have suggested an index of best management practices capturing three broad areas: monitoring, targets and incentives. However, it is an open question whether the functioning of these practices depends on contextual factors. From a theoretical viewpoint, the management practices involve both productive and dysfunctional effects. We hypothesize that the relative strength of these effects depends on the industrial relations climate. Works councils help management practices live up to their potential by building long‐term employer‐employee cooperation. Our empirical analysis uses panel data from the German Management and Organizational Practices survey to examine this hypothesis. Applying a reformulated version of the Mundlak estimator, we disentangle short‐term and sustaining productivity effects of the management practices. Our results show that the incidence of a works council specifically strengthens the sustaining productivity effect of the practices.
Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment option for lower thoracic oesophageal cancer with supraclavicular lymph node metastasis: An inverse probability of treatment‐weighted analysis of SEER database
Authors: Chang Xiao , Liu Jiayue , Zhao Yuting , Shi Anhui , Yu Huiming , Yu Rong , Wang Weihu
Published: July 2023

Introduction

Whether supraclavicular lymph node (SCLN) metastasis in patients with oesophageal cancer belongs to regional disease is controversial, leading to heterogeneity in clinical treatment decisions. This study aimed to determine the optimal treatment for lower thoracic oesophageal cancer (LTOC) with SCLN metastasis.

Methods

Patients with LTOC registered in the Surveillance, Epidemiology, and End Results database during 2010–2015 were identified. Selected patients were grouped according to disease spread as those with locoregional disease, with SCLN metastasis or with distant metastasis, as well as according to treatment modality (neoadjuvant chemoradiotherapy followed by surgery (nCRT+S group), upfront surgery ± adjuvant therapy (upfront S group) and definitive chemoradiotherapy (dCRT group)). The Cox regression analysis and inverse probability of treatment weighting (IPTW) were used to identify the optimal treatment modality for different groups.

Results

Of 11,767 LTOC patients identified from the database, the 5‐year overall survival (OS) rates for patients with the locoregional disease (n = 7,541), SCLN metastasis (n = 120) and distant metastasis (n = 4,106) were 28.3%, 10.0% and 3.0%, respectively (P < 0.001). Among patients with SCLN metastasis, median OS in the nCRT+S, upfront S and dCRT groups were 25, 14 and 8 months, respectively (P < 0.001). After IPTW, the nCRT+S group was still associated with better median OS compared with other groups. The multivariate analysis identified treatment modality as an independent prognostic factor for OS.

Conclusions

Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment modality for LTOC with SCLN metastasis. The findings of this study need to be validated in large prospective studies.
Spineless and overlooked: DNA metabarcoding of autonomous reef monitoring structures reveals intra‐ and interspecific genetic diversity in Mediterranean invertebrates
Authors: Thomasdotter Anna , Shum Peter , Mugnai Francesco , Vingiani Marina , Dubut Vincent , Marschal Florent , Abbiati Marco , Chenuil Anne , Costantini Federica
Published: July 2023

The ability to gather genetic information using DNA metabarcoding of bulk samples obtained directly from the environment is crucial to determine biodiversity baselines and understand population dynamics in the marine realm. While DNA metabarcoding is effective in evaluating biodiversity at community level, genetic patterns within species are often concealed in metabarcoding studies and overlooked for marine invertebrates. In the present study, we implement recently developed bioinformatics tools to investigate intraspecific genetic variability for invertebrate taxa in the Mediterranean Sea. Using metabarcoding samples from Autonomous Reef Monitoring Structures (ARMS) deployed in three locations, we present haplotypes and diversity estimates for 145 unique species. While overall genetic diversity was low, we identified several species with high diversity records and potential cryptic lineages. Further, we emphasize the spatial scale of genetic variability, which was observed from locations to individual sampling units (ARMS). We carried out a population genetic analysis of several important yet understudied species, which highlights the current knowledge gap concerning intraspecific genetic patterns for the target taxa in the Mediterranean basin. Our approach considerably enhances biodiversity monitoring of charismatic and understudied Mediterranean species, which can be incorporated into ARMS surveys.
Overlapping drug‐induced vasculitis, ANCA‐associated vasculitis, and lupus nephritis caused by low‐dose hydralazine
Authors: Bhatnagar M. , Agaronov A. , Sarkisyan E. , Sotoudeh Deilamy I. , Pepito D. , Akhondi H.
Published: July 2023

Introduction

We present a case of drug‐induced vasculitis secondary to low‐dose hydralazine with overlapping features of antineutrophil cytoplasmic antibody‐associated vasculitis and drug‐induced lupus nephritis.

Case presentation

A 52‐year‐old Hispanic woman with a medical history of resistant hypertension treated with hydralazine 10 mg twice daily for 1 year presented with generalized weakness, dizziness, nausea, vomiting, and gross hematuria. There was fever, tachycardia, leukocytosis, lactic acidosis, hyperkalemia, renal failure, and anemia. Chest computed tomography and bronchoscopy revealed a left lower lobe infiltrate and diffuse alveolar hemorrhage. Serologic testing was positive for anti‐double‐stranded DNA, anti‐Smith, lupus anticoagulant, anti‐histone, anti‐cardiolipin IgM antibodies, and antineutrophil cytoplasmic antibodies (myeloperoxidase and proteinase 3). A kidney biopsy revealed crescentic glomerulonephritis with an overlapping finding of membranous nephropathy. Broad‐spectrum antibiotics, immunosuppressants, corticosteroids, and plasmapheresis were initiated. The patient survived but required continuous hemodialysis.

Conclusions

Although a few cases of simultaneous antibody‐associated vasculitis and drug‐induced lupus nephritis secondary to hydralazine use have been reported, this case is singular. Similar findings were previously reported with doses of 50–100 mg two to three times daily over 1–5 years. In our patient, a dose of only 10 mg twice daily for a year caused a severe disease presentation. This brings to light the combination of different vasculitides that can coexist and the potentially life‐threatening adverse effects of low‐dose hydralazine that should be kept in mind.
Psychological support and patient‐centered care for patients with rheumatoid arthritis: Nurses' opinions and practice in Japan
Authors: Fusama Mie , Motonaga Takuro , Kuroe Yuriko , Nakahara Hideko
Published: July 2023

Aim

To investigate nurses' opinions and practices regarding psychological support and patient‐centered care (PCC) for patients with rheumatoid arthritis.

Method

Registered nurses engaged in rheumatic care in Japan were asked to complete the questionnaire regarding nurses' perceived necessity, understanding, and implementation of psychological support, and six patient supports related to PCC, using a seven‐point Likert scale. Correlation on practice between psychological support and PCC was evaluated.

Results

A total of 53 nurses participated. Nurses indicated high necessity of providing psychological support, whereas implementation was statistically significantly lower than necessity and motivation. Nurses' answers showed significantly lower implementation compared with understanding regarding basic concepts of psychological support: listening, empathy, acceptance, open questions, and closed questions. Most nurses (54.7%) sometimes provided psychological support, followed by often (34.0%), always (5.7%), and not at all (5.6%). Perceived necessity of PCC was rated high. However, its implementation was significantly lower than necessity for all evaluated cares, such as patients' need‐based support and support to patients' families, related to PCC. Positive correlations were observed between the implementation of psychological support and PCC. Nurses stressed the importance of psychological support for patient education and shared decision‐making.

Conclusion

This preliminary study indicated that most nurses considered psychological support and PCC necessary, but their implementation was relatively low. As psychological support is also crucial to shared decision‐making, in addition to PCC, barriers to its implementation should be addressed to improve patients' outcomes and quality of life.
Photosynthetic nitrogen utilization of Robinia pseudoacacia, an invasive species, grown in contrasting light conditions: A leaf scale approach
Authors: Kitaoka Satoshi , Qu Laiye , Kanetoshi Masaharu , Watanabe Yoko , Fujita Saki , Koike Takayoshi
Published: July 2023

Robinia pseudoacacia (black locust), an alien species in Japan, has been commonly planted to rehabilitate degraded land and as a resource for the production of honey. Although very few R. pseudoacacia adult trees are found in established mature forests, the management of R. pseudoacacia is a vital and urgent matter because of astounding growth potential, which negatively affects biodiversity and native vegetation. For this reason, we evaluated the seasonal shade‐acclimation capacity of black locusts from the viewpoint of photosynthetic nitrogen use (PNU) and their partitioning. We assessed in situ photosynthetic N use traits of R. pseudoacacia leaves at open sites (relative photosynthetic photon flux density: (rPPFD) > 90%) and shaded sites (rPPFD < 22%) on the forest floor in larch (Larix kaempferi Carr.) plantations. Leaf unfolding started in late May and leaves turned yellow by mid‐October just before leaf shedding. Shoot length at open sites was three times longer than at shaded sites. R. psudoacacia at open sites has more the leaflet number of each pinnate compound leaf than shaded sites from mid‐August to October, and the size of leaflets at shaded sites was about 20% smaller than it was at the open sites. Leaf mass per area showed (mean ± standard deviation) 40.00 ± 2.14 g m−2 at the open sites and 22 ± 1.56 g m−2 at the shaded sites from June to October. The light‐saturated photosynthetic rate peaked at 22 μmol m−2 s−1 at the open sites in July. At the shaded sites, it gradually increased to 7–10 μmol m−2 s−1 around August, and then decreased at both sites toward zero in mid‐October. The total N content during the growth period was 1.60 ± 0.17 g m−2 at open sites and 1.16 ± 0.15 g m−2 at shaded sites. Unlike other tree species, N partitioning to photosynthetic organs was not affected by light conditions. These findings suggested R. psudoacacia cannot acclimate to shady conditions.
Telephone follow‐up after early medical abortion using Australia's first low sensitivity urine pregnancy test
Authors: Melville Catriona , Goldstone Philip , Moosa Nisreen
Published: July 2023

Background

Follow‐up after early medical abortion (EMA) in Australia often entails tracking serum human chorionic gonadotropin levels or performing ultrasonography in‐clinic. In other countries, methods of follow‐up such as using a low‐sensitivity urine pregnancy test (LSUPT), telephone evaluation and a questionnaire have been demonstrated to be safe and acceptable.

Aims

To evaluate the safety and efficacy of telephone follow‐up after EMA using an LSUPT and questionnaire.

Materials and Methods

A prospective observational cohort study of patients undergoing telephone follow‐up after EMA using an LSUPT and questionnaire was conducted from March 26 to July 31, 2020. Outcomes of patients who returned to clinic because of a positive LSUPT were evaluated and adverse event rates were calculated. Routinely collected adverse event information was used to compare complication rates during the evaluation period with that prior to introduction of the LSUPT.

Results

During the study period, 2223 patients underwent the new protocol. One hundred and ninety‐seven patients had a positive LSUPT at their telephone follow‐up. One hundred and thirty‐two had an incomplete abortion, 11 had a continuing pregnancy, 53 had a complete abortion and one left the clinic before full assessment.

Conclusions

Introduction of telephone follow‐up with an at‐home LSUPT reduced the number of patients requiring unnecessary clinic appointments, with over 90% of patients completing their follow‐up at home. Complication rates during the study period were found to be at least comparable with previously identified organisational adverse events.
Foundations of support: Processes associated with adolescents supporting a peer who experienced a traumatic event
Authors: Dolan Erin , Cosgrave Catherine , Killackey Eóin , Allott Kelly
Published: July 2023

Background

There is limited research on how supporting a peer through a traumatic event is experienced by adolescents. The aim of this research was to understand the personal and interpersonal processes of adolescents supporting a peer who experienced a traumatic event based on youth definitions.

Method

In‐depth qualitative interviews were conducted with 22 adolescents aged 14–19, residing in Gippsland, Victoria, Australia. A constructivist grounded theory methodology was used to develop a substantive theory.

Results

The substantive theory ‘Foundations of Support’ was developed which explained the support process phenomena. Specifically, adolescents who had shared responsibility for supporting their peers went back to life as normal, whereas adolescents who maintained sole responsibility experienced mental health problems.

Discussion

The ‘Foundations of Support’ grounded theory highlights the importance of adolescents having strong connections to their trusted others, such as family, friends and community. This theory implies that facilitating connections with positive supports such as place and community are essential in guiding adolescents back to their foundations of support. Without strong connections, adolescents are at risk of maintaining sole responsibility, losing their sense of identity and feeling alienated within their community.
The allopurinol metabolite, oxypurinol, drives oligoclonal expansions of drug‐reactive T cells in resolved hypersensitivity cases and drug‐naïve healthy donors
Authors: Mifsud Nicole A. , Illing Patricia T. , Ho Rebecca , Tuomisto Johanna E. , Fettke Heidi , Mullan Kerry A. , McCluskey James , Rossjohn Jamie , Vivian Julian , Reantragoon Rangsima , Purcell Anthony W.
Published: July 2023

Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to life‐threatening reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Individuals who carry the human leukocyte antigen (HLA)‐B*58:01 allotype are at higher risk of experiencing a hypersensitivity reaction (odds ratios ranging from 5.62 to 580.3 for mild to severe reactions, respectively). In addition to the parent drug, the metabolite oxypurinol (OXP) is implicated in triggering T cell‐mediated immunopathology via a labile interaction with HLA‐B*58:01. To date, there has been limited information regarding the T‐cell receptor (TCR) repertoire usage of reactive T cells in patients with ALP‐induced SJS or TEN and, in particular, there are no reports examining paired αβTCRs. Here, using in vitro drug‐treated PBMCs isolated from both resolved ALP‐induced SJS/TEN cases and drug‐naïve healthy donors, we show that OXP is the driver of CD8+ T cell‐mediated responses and that drug‐exposed memory T cells can exhibit a proinflammatory immunophenotype similar to T cells described during active disease. Furthermore, this response supported the pharmacological interaction with immune receptors (p‐i) concept by showcasing (i) the labile metabolite interaction with peptide/HLA complexes, (ii) immunogenic complex formation at the cell surface, and (iii) lack of requirement for antigen processing to elicit drug‐induced T cell responsiveness. Examination of paired OXP‐induced αβTCR repertoires highlighted an oligoclonal and private clonotypic profile in both resolved ALP‐induced SJS/TEN cases and drug‐naïve healthy donors.
Perinatal outcomes after therapeutic rest in the latent phase of labor: A cohort study
Authors: Bagger Nanna T. , Milidou Ioanna , Boie Sidsel , Glavind Julie
Published: July 2023

Introduction

Therapeutic rest refers to the usage of medication to relieve pain in women in the latent phase of labor. Very few data are available to evaluate the safety and effect of its use.

The objectives of this study were to compare perinatal and labor outcomes in women who were seeking hospital care during the latent phase of labor and who were treated either with or without therapeutic rest.

Material and methods

Retrospective cohort study with inclusion of nulliparous singleton pregnant women in the latent phase of labor presenting at the labor ward at Aarhus University Hospital, Denmark from May 13, 2018 to June 1, 2021. We identified two groups: women who were treated with therapeutic rest and women who were not. The primary outcomes were neonatal admission and neonatal resuscitation. Secondary outcomes included use of cardiotocography during labor, nonreactive fetal heart rate, meconium‐stained amniotic fluid, pediatric delivery room assistance, umbilical cord arterial pH and standard base excess, Apgar score at 5 minutes, interventions during labor and mode of delivery.

Results

In our sample of 800 women in the latent phase of labor, 414 women (52%) were treated with therapeutic rest and 386 women (48%) were not. The most frequently used (n = 206) medication for therapeutic rest was a combination of paracetamol, triazolam and codeine. We found no significant difference in neonatal admission (9.2% vs 6.5%, adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.4–3.1) or neonatal resuscitation (2.4% vs 3.1%, aOR 0.7, 95% CI 0.1–4.0) between women treated with or without therapeutic rest. There were no differences between the two groups in other perinatal adverse outcomes, interventions during labor or mode of delivery.

Conclusions

This study found no significant association between therapeutic rest and neonatal admission or resuscitation. Our findings indicate that therapeutic rest is a safe method for managing the latent phase of labor concerning neonatal health and does not increase the risk of labor complications.
Comparison of perimetric 24‐2 and 30‐2 test patterns in detecting visual field defects in patients with tumours in the pituitary region
Authors: Gesslein Bodil , Naumovska Magdalena , Neumann Olof , Bizios Dimitrios , Bengtsson Boel , Siesjö Peter , Uvelius Erik , Hammar Björn , Sheikh Rafi
Published: July 2023

Purpose

Automated perimetry provides a standardized method of measuring the visual field. The Humphrey Field Analyser (HFA) uses the 24‐2 test pattern to cover 24 degrees centrally or the 30‐2 test pattern to cover a slightly broader region of 30 degrees. The aim of this study was to determine whether the 24‐2 test pattern provides comparable information to the 30‐2 test pattern in detecting visual field defects in patients with tumours in the pituitary region.

Methods

A retrospective cohort study was carried out on patients with tumours in the pituitary region and radiologically confirmed compression of the visual pathway. Included patients (79 of 133) had been examined using the Humphrey 30‐2 visual field test, after which the 30‐2 test patterns were reduced into corresponding 24‐2 test patterns. The location of visual field defects, visual acuity and the perimetric parameters mean deviation (MD) and visual field index (VFI) were also recorded.

Results

No patient was classified differently when evaluated with the 24‐2 test pattern, compared to the 30‐2 test pattern. Interestingly, although the majority of patients had visual field defects located in the temporal visual field of each eye, a significant minority did not. In addition, it was found that a large proportion of patients had normal visual acuity (≥0.8).

Conclusions

The use of the HFA 24‐2 test pattern reliably detected visual field defects in patients with tumours in the pituitary region. The present study indicates that MD and VFI are not reliable parameters for evaluating visual field defects due to compression.
Editorial: Pip pip to PIP's (post‐inflammatory polyps) as a neoplasia risk factor in IBD?
Authors: Velayos Fernando S.
Published: July 2023

LINKED CONTENT

This article is linked to Wolf et al papers. To view these articles, visit https://doi.org/10.1111/apt.17495 and https://doi.org/10.1111/apt.17612
In search of a better method to distinguish artefacts from geofacts
Authors: Wiśniewski Andrzej , Różycka Milena , Schunk Lisa
Published: July 2023

Archaeologists use a method of evaluating the characteristics of flakes, called scoring, to distinguish geofacts (pseudo‐artefacts or eoliths) from artefacts. Lower total scores are considered indicative of a natural source of the finds, while higher ones support the opposite. However, this method has some limitations. The most important are the small quantity of assemblages subject to such an analysis and the unclear boundary drawn by a ranking within a point‐based score evaluation between collections with finds of cultural and anthropic origin. Here, we present a method that minimizes these limitations. It consists of a statistical approach using scoring percentages, a new method of visualizing them and the application of clustering. This way, we obtained clear differences between pseudo‐artefacts and artefacts by considering flakes from six flint assemblages from Central Europe as well as an experimental assemblage.
Heroin metabolism in human blood and its impact for the design of an immunotherapeutic approach against heroin effects
Authors: Bogen Inger Lise , Boix Fernando , Andersen Jannike Mørch , Steinsland Synne , Nerem Elisabeth , Mørland Jørg
Published: July 2023

Immunotherapeutic interventions that block drug effects by binding drug molecules to specific antibodies in the bloodstream have shown promising effects in animal studies. For heroin, which effects are mainly mediated by the metabolites 6‐acetylmorphine (6‐AM; also known as 6‐monoacetylmorphine or 6‐MAM) and morphine, the optimal antibody specificity has been discussed. In rodents, 6‐AM specific antibodies have been recommended based on the rapid metabolism of heroin to 6‐AM in the bloodstream. Since the metabolic rate of heroin in blood is unsettled in humans, we examined heroin metabolism with state‐of–the‐art analytical methodology (UHPLC–MS/MS) in freshly drawn human whole blood incubated with a wide range of heroin concentrations (1–500 μM). The half‐life of heroin was highly concentration dependent, ranging from 1.2–1.7 min for concentrations at or above 25 μM, and gradually increasing to approximately 20 min for 1 μM heroin. At concentrations that can be attained in the bloodstream shortly after an i.v. injection, approximately 70% was transformed into 6‐AM within 3 min, similar to previous observations in vivo. Our results indicate that blood enzymes play a more important role for the rapid metabolism of heroin in humans than previously assumed. This points to 6‐AM as an important target for an efficient immunotherapeutic approach to block heroin effects in humans.
A world of difference: The fundamental opposition between transhumanist “welfarism” and disability advocacy
Authors: Levin Susan B.
Published: July 2023

From the standpoint of disability advocacy, further exploration of the concept of well‐being stands to be availing. The notion that “welfarism” about disability, which Julian Savulescu and Guy Kahane debuted, qualifies as helpful is encouraged by their claim that welfarism shares important commitments with that advocacy. As becomes clear when they apply their welfarist frame to procreative decisions, endorsing welfarism would, in fact, sharply undermine it. Savulescu and Kahane's Principle of Procreative Beneficence—which reflects transhumanism, or advocacy of radical bioenhancement—morally requires parents to choose the child who will, in all probability, have “the best life.” Assuming the emergence of potent biotechnologies, procreative decision‐making would be highly standardized, for prospective parents would be morally obliged to maximize select capacities, including intelligence, self‐control, and hedonic set‐point, in their children. Welfarism, applied to reproduction, is staunchly objectivist about what course is incumbent on decision‐makers, giving no credence to first‐personal values, aspirations, and experiences. Though this dismissal of individual perspectives applies to everyone, its implications for disability advocacy are especially severe. With that advocacy in view, greater attention to “well‐being” should, therefore, be severed from the welfarism of Savulescu and Kahane.
International comparisons of the home mathematics environment and relations with children's mathematical achievement
Authors: Ellis Alexa , Cosso Jimena , Duncan Robert J. , Susperreguy María Inés , Simms Victoria , Purpura David J.
Published: July 2023

Background

Home mathematics environment (HME) research has focused on parent–child interactions surrounding numerical activities as measured by the frequency of engaging in such activities. However, HME survey questions have been developed from limited perspectives (e.g., Early Childhood Research Quarterly, 27, 2012, 231; Journal of Social Issues, 64, 2008, 95; Early childhood mathematics education research: Learning trajectories for young children, Routledge, New York, 2009), by researchers from a small subset of countries (15; Psychological Bulletin, 147, 2020, 565), which may skew our interpretations.

Aims and Sample

This study broadened international representation by leveraging secondary data from the 2019 TIMSS to examine the variation of the frequency and reliability of the HME scale and its relation to children's mathematical achievement. Across 54 countries, 231,138 parents and children (Mage = 10.22 years; 51% male) participated in the larger study.

Methods

Parents completed a retrospective home environment survey and children were assessed on mathematics skills. Basic frequency descriptive statistics, Cronbach's alpha reliability coefficients, and Pearson's r correlation coefficients were used to assess variability across countries.

Results

Findings suggested that families in certain countries engaged in home mathematics activities more frequently than families in other countries; however, the HME scale demonstrated acceptable internal consistency across families in all countries (M α = .79; range = [.73, .89]). Further, the average relation between HME and mathematical achievement was r = .15 with a range between r = .02 to r = .41.

Conclusion

Our results indicate substantial variation across countries in the HME‐mathematical achievement association. These findings underscore the importance of international representation in advancing research on the diversity of a child's home environment.
Nano‐delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives
Authors: Movahedpour Ahmad , Taghvaeefar Rasul , Asadi‐Pooya Ali‐Akbar , Karami Yousof , Tavasolian Ronia , Khatami Seyyed Hossein , Soltani Fard Elahe , Taghvimi Sina , Karami Neda , Rahimi Jaberi Khojaste , Taheri‐Anganeh Mortaza , Ghasemi Hassan
Published: July 2023

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood–brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle‐based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano‐delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.
The G protein‐coupled estrogen receptor of the trigeminal ganglion regulates acute and chronic itch in mice
Authors: Li Jun , Gao Po , Zhang Siyu , Lin Xiaoqi , Chen Junhui , Zhang Song , Jiao Yingfu , Yu Weifeng , Xia Xiaoqiong , Yang Liqun
Published: July 2023

Aims

Itch is an unpleasant sensation that severely impacts the patient's quality of life. Recent studies revealed that the G protein‐coupled estrogen receptor (GPER) may play a crucial role in the regulation of pain and itch perception. However, the contribution of the GPER in primary sensory neurons to the regulation of itch perception remains elusive. This study aimed to investigate whether and how the GPER participates in the regulation of itch perception in the trigeminal ganglion (TG).

Methods and Results

Immunofluorescence staining results showed that GPER‐positive (GPER+) neurons of the TG were activated in both acute and chronic itch. Behavioral data indicated that the chemogenetic activation of GPER+ neurons of the TG of Gper‐Cre mice abrogated scratching behaviors evoked by acute and chronic itch. Conversely, the chemogenetic inhibition of GPER+ neurons resulted in increased itch responses. Furthermore, the GPER expression and function were both upregulated in the TG of the dry skin‐induced chronic itch mouse model. Pharmacological inhibition of GPER (or Gper deficiency) markedly increased acute and chronic itch‐related scratching behaviors in mouse. Calcium imaging assays further revealed that Gper deficiency in TG neurons led to a marked increase in the calcium responses evoked by agonists of the transient receptor potential ankyrin A1 (TRPA1) and transient receptor potential vanilloid V1 (TRPV1).

Conclusion

Our findings demonstrated that the GPER of TG neurons is involved in the regulation of acute and chronic itch perception, by modulating the function of TRPA1 and TRPV1. This study provides new insights into peripheral itch sensory signal processing mechanisms and offers new targets for future clinical antipruritic therapy.
Monocyte‐related cytokines/chemokines in cerebral ischemic stroke
Authors: Bai Meiling , Sun Ruize , Cao Bin , Feng Juan , Wang Jue
Published: July 2023

Aims

Ischemic stroke is one of the leading causes of death worldwide and the most common cause of disability in Western countries. Multiple mechanisms contribute to the development and progression of ischemic stroke, and inflammation is one of the most important mechanisms.

Discussion

Ischemia induces the release of adenosine triphosphate/reactive oxygen species, which activates immune cells to produce many proinflammatory cytokines that activate downstream inflammatory cascades to induce fatal immune responses. Research has confirmed that peripheral blood immune cells play a vital role in the immunological cascade after ischemic stroke. The role of monocytes has received much attention among numerous peripheral blood immune cells. Monocytes induce their effects by secreting cytokines or chemokines, including CCL2/CCR2, CCR4, CCR5, CD36, CX3CL1/CX3CR1, CXCL12(SDF‐1), LFA‐1/ICAM‐1, Ly6C, MMP‐2/9, NR4A1, P2X4R, P‐selectin, CD40L, TLR2/4, and VCAM‐1/VLA‐4. Those factors play important roles in the process of monocyte recruitment, migration, and differentiation.

Conclusion

This review focuses on the function and mechanism of the cytokines secreted by monocytes in the process of ischemic stroke and provides novel targets for treating cerebral ischemic stroke.
Prevalence and utility of pharmacokinetic data in preclinical studies of mRNA cancer vaccines
Authors: Roth Gillie A. , Vora Bianca , Kim Chloe , Wu Michael , Kuruvilla Denison
Published: July 2023

In this brief report, we provide insights into current practices in preclinical messenger RNA (mRNA) cancer vaccine characterization. To enable a more automated and thorough survey of mRNA cancer vaccine data in the literature, we implemented natural language processing to mine abstracts from PubMed followed by annotation of the selected articles. Through this analysis we identified a gap in the literature wherein pharmacokinetic (PK) characterization is not reported in mRNA cancer vaccine‐focused articles. As a result, the field is unable to evaluate and discuss cross‐study PK and pharmacodynamic (PD) relationships nor the translation of these relationships from preclinical species to humans. As the field of mRNA cancer vaccines is rapidly evolving, there is value in expanding our understanding of preclinical PK/PD relationships and how they relate to PK/PD in humans.
1064. Agapetes grandiflora Hook.f.: Ericaceae
Authors: Murata Jin , Murata Hiroko , Yamanaka Masumi
Published: July 2023

A specimen of Agapetes from Myanmar is described and illustrated as Agapetes grandiflora Hook.f., as a result of comparison with A. burmanica W.E.Evans, A. macrantha (Hook.) Hook.f. and A. variegata (Roxb.) D.Don ex G.Don. This species has extrafloral nectaries on the margins of young leaves and at the apex of calyx lobes.
Qualitative study of states' capacity to support alcohol prevention policies during the COVID‐19 pandemic in the USA
Authors: Haley Sean J. , Peddireddy Snigdha , El‐Harakeh Amena , Akasreku Bridget , Riibe Diane
Published: July 2023

Introduction

The onset of the COVID‐19 pandemic accelerated rates of alcohol purchasing and related harms in the USA. The increases followed governors' emergency orders that increased alcohol availability, including the allowance of alcohol home delivery, alcohol to‐go from restaurants and bars, and curbside pickup from retailers.

Methods

Semi‐structured interviews were conducted with 53 participants involved in state‐level alcohol prevention policy across 48 states. Interviewees' perspectives on changes to alcohol prevention policies during the COVID‐19 pandemic, including capacity to respond to alcohol‐focused executive and legislative changes to alcohol availability, were explored. Initial codes were developed collectively and refined through successive readings of transcripts using a phenomenological, action‐oriented research approach. Themes were identified semantically after all transcripts were coded and reviewed.

Results

Four themes were developed including: (i) alcohol prevention policies and capacity during COVID‐19; (ii) industry‐related challenges during COVID‐19; (iii) limited pre‐COVID‐19 alcohol prevention capacity; and (iv) needs to strengthen alcohol prevention capacity.

Discussion and Conclusions

The pandemic exacerbated states' capacity limitations for alcohol prevention efforts and created additional impediments to public health messaging about alcohol health risks related to greater alcohol availability. Participants offered a myriad of strategies to improve alcohol prevention and to reduce alcohol‐related harms. Recommendations included dedicated federal and state prioritisation, more funding for community organisations, greater coordination, consistent high‐quality trainings, stronger surveillance and widespread prevention messaging. States' alcohol prevention efforts require dedicated leadership, additional funding and support to strengthen population‐based strategies to reduce sustained alcohol‐related harms associated with increases in alcohol availability.
Methamphetamine and emerging drugs of concern: A training needs analysis of Australian alcohol and other drug helplines
Authors: Bascombe Florence , Siefried Krista J. , Clifford Brendan , Child Stacey , Loos Rick , Sgouras Hazel , Stevens Lynn , Wilson Hollie , Ezard Nadine
Published: July 2023

Introduction

Fielding greater than 100,000 calls annually, telephone helplines are an important point of entry to alcohol and other drug (AOD) support and services in Australia. Methamphetamine and emerging drugs can present a particular challenge for this workforce. We sought to identify training needs for these services, so that appropriate targeted resources can be developed.

Methods

We distributed an anonymous, online, cross‐sectional survey to helpline staff from New South Wales, Queensland, South Australia, Victoria and Western Australia. Based on the WHO Hennessy‐Hicks training needs analysis tool, participants were asked: to rate on a 7‐point likert scale the importance of a topic to their practice and how well they perform in relation to the topic; open‐ended questions specifying their own self‐perceived training needs; and demographic data.

Results

Of 50 participants, 29 completed the full survey (median age 49 [IQR 30–57.5]; median time working in AOD sector 6 years [IQR 1–20]). The results identified a need for: practical community‐informed population relevant information for culturally and linguistically diverse populations and Aboriginal and Torres Strait Islander peoples for calls relating to methamphetamine and emerging drugs of concern; training and resources with a particular focus on families and friends of people who use methamphetamine and emerging drugs; and readily accessible up‐to‐date information on new and emerging drugs and treatment of related disorders.

Discussion and Conclusions

This training needs analysis provides a structured approach to supporting the first‐line AOD counsellors to provide up‐to‐date and accurate information to assist Australians seeking information, support and advice.
Dysregulated TDP‐43 proteostasis perturbs excitability of spinal motor neurons during brainstem‐mediated fictive locomotion in zebrafish
Authors: Asakawa Kazuhide , Handa Hiroshi , Kawakami Koichi
Published: July 2023

Spinal motor neurons (SMNs) are the primary target of degeneration in amyotrophic lateral sclerosis (ALS). Degenerating motor neurons accumulate cytoplasmic TAR DNA‐binding protein 43 (TDP‐43) aggregates in most ALS cases. This SMN pathology can occur without mutation in the coding sequence of the TDP‐43‐encoding gene, TARDBP. Whether and how wild‐type TDP‐43 drives pathological changes in SMNs in vivo remains largely unexplored. In this study, we develop a two‐photon calcium imaging setup in which tactile‐evoked neural responses of motor neurons in the brainstem and spinal cord can be monitored using the calcium indicator GCaMP. We devise a piezo‐assisted tactile stimulator that reproducibly evokes a brainstem descending neuron upon tactile stimulation of the head. A direct comparison between caudal primary motor neurons (CaPs) with or without TDP‐43 overexpression in contiguous spinal segments demonstrates that CaPs overexpressing TDP‐43 display attenuated Ca2+ transients during fictive escape locomotion evoked by the tactile stimulation. These results show that excessive amounts of TDP‐43 protein reduce the neuronal excitability of SMNs and potentially contribute to asymptomatic pathological lesions of SMNs and movement disorders in patients with ALS.
Pcgf1 gene disruption reveals primary involvement of epigenetic mechanism in neuronal subtype specification in the enteric nervous system
Authors: Putra Bayu Pratama , Ito Keisuke , Cirillo Carla , Sunardi Mukhamad , Koseki Haruhiko , Uesaka Toshihiro , Enomoto Hideki
Published: July 2023

The enteric nervous system (ENS) regulates gut functions independently from the central nervous system (CNS) by its highly autonomic neural circuit that integrates diverse neuronal subtypes. Although several transcription factors are shown to be necessary for the generation of some enteric neuron subtypes, the mechanisms underlying neuronal subtype specification in the ENS remain elusive. In this study, we examined the biological function of Polycomb group RING finger protein 1 (PCGF1), one of the epigenetic modifiers, in the development and differentiation of the ENS by disrupting the Pcgf1 gene selectively in the autonomic‐lineage cells. Although ENS precursor migration and enteric neurogenesis were largely unaffected, neuronal differentiation was impaired in the Pcgf1‐deficient mice, with the numbers of neurons expressing somatostatin (Sst+) decreased in multiple gut regions. Notably, the decrease in Sst+ neurons was associated with the corresponding increase in calbindin+ neurons in the proximal colon. These findings suggest that neuronal subtype conversion may occur in the absence of PCGF1, and that epigenetic mechanism is primarily involved in specification of some enteric neuron subtypes.