bluuebunny/crossref_metadata_2025 huggingface dataset:
Female reproductive fluid and male seminal fluid: a non-gametic conflict for post-mating control
Authors: Pinzoni Livia , Locatello Lisa , Gasparini Clelia , Rasotto Maria Berica
Published: September 2023

Growing evidence shows that non-gametic components released by both males and females can significantly drive sperm competition outcomes. Seminal fluid (SF) was shown to influence paternity success by affecting rival males' sperm performance, and, in some species with male alternative reproductive tactics, to selectively decrease the fertilization success of males of the opposite tactic. Female reproductive fluid (FRF) has been proven to differentially influence ejaculates of different males and bias fertilization towards specific partners. Whether, and with what outcome, these two processes can intersect to influence sperm competition is still unknown. Here we explore this scenario in the grass goby (
Zosterisessor ophiocephalus),
a fish with territorial–sneaker reproductive tactics, where sneaker males can exploit the territorials’ SF while penalizing territorial sperm performance with their own fluid. To test whether FRF can rebalance the ejaculate competition in favour of territorial males, we used
in vitro
fertilization with a SF mixture (territorial + sneaker), using increasing concentrations of FRF, to simulate the natural conditions that ejaculates encounter towards the eggs. Our findings revealed a differential effect of FRF on the different tactics' fertilization success, favouring territorial ejaculates, possibly through an attenuation of the detrimental effects of sneaker SF, and enabling females to regain control over the fertilization process.
A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS
Authors: Gordon Blair , Allum Fiona , Brooks Michael , Rajakulendran Nishani , Rampakakis Emmanouil , Sampalis John ,   EB05 Study Investigators
Published: September 2023

Background

Coronavirus disease 2019 (COVID-19) mortality is predominantly due to acute respiratory distress syndrome (ARDS). There are currently limited treatment options for ARDS, a life-threatening condition with different etiologies, secondary to inflammation-induced lung injury. Paridiprubart is a monoclonal antibody that inhibits Toll-like Receptor 4 (TLR4), a key player in ARDS pathophysiology.

Methods

This was a prespecified sub-study of a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy and safety of paridiprubart in COVID-19 patients with ARDS receiving invasive mechanical ventilation and additional organ support. Efficacy outcomes were 28- and 60-day all-cause mortality, and improvement in COVID-19 severity and ventilation-free days at 28-days post-treatment.

Results

Thirteen (13) and twenty (20) patients received paridiprubart and placebo, respectively. The groups were comparable for demographics and baseline parameters, except for higher kidney failure incidence and use of immune modulators and antivirals, and lower corticosteroids use in the paridiprubart group. Mortality at 28-days post-treatment was 7.7% (1/13) in the paridiprubart group versus 40.0% (8/20) for placebo (OR=0.125; 95% CI, 0.013-1.160; P=0.067; P[bootstrap]=0.011). 60-day mortality was 23.1% (3/13) in paridiprubart-treated patients and 45.0% (9/20) in placebo patients (OR=0.367; 95% CI, 0.077-1.749; P=0.208; P[bootstrap]=0.162). Mean survival time was 55.78 days for paridiprubart recipients compared to 41.44 days for placebo patients (HR=0.386; 95% CI, 0.077-1.436; P=0.156; P[bootstrap]=0.083). Although not statistically significant, results for other efficacy measures favored paridiprubart. Incidence of adverse events was similar in both groups.

Conclusions

In COVID-19 patients with ARDS requiring invasive ventilation and organ support, paridiprubart was efficacious in preventing mortality and improving clinical outcomes, with no safety concerns.
Absolute number of three populations of interneurons and all GABAergic synapses in the human hippocampus
Authors: Takács Virág , Papp Péter , Orosz Áron , Bardóczi Zsuzsanna , Zsoldos Tamás , Zichó Krisztián , Watanabe Masahiko , Maglóczky Zsófia , Gombás Péter , Freund Tamás F. , Nyiri Gábor
Published: September 2023

The human hippocampus, essential for learning and memory, is implicated in numerous neurological and psychiatric disorders, each linked to specific neuronal subpopulations. Advancing our understanding of hippocampal function requires computational models grounded in precise quantitative neuronal data. While extensive data exist on the neuronal composition and synaptic architecture of the rodent hippocampus, analogous quantitative data for the human hippocampus remain very limited. Given the critical role of local GABAergic interneurons in modulating hippocampal functions, we employed unbiased stereological techniques to estimate the density and total number of three major GABAergic cell types in the human hippocampus: parvalbumin (PV)-expressing, somatostatin (SOM)-positive, and calretinin (CR)-positive interneurons. Our findings reveal an estimated 49,400 PV-positive, 141,500 SOM-positive, and 250,600 CR-positive interneurons per hippocampal hemisphere. Notably, the higher proportion of CR-positive, primarily interneuron-selective, cells in humans, compared to rodents, may enhance local interneuron regulation. Additionally, using 3-dimensional electron microscopy, we estimated approximately 25 billion GABAergic synapses per hippocampal hemisphere, with PV-positive boutons comprising around 3.5 billion synapses, or 14% of the total GABAergic synapses. These findings contribute crucial quantitative insights for modeling human hippocampal circuits and understanding its complex regulatory dynamics.
How does language intensity of brand fan word-of-mouth (WOM) affect customers' willingness to adopt WOM? An empirical study based on psychological resistance theory
Authors: Zhang Depeng , Li Zhongxiang , Ma Jiaxin
Published: September 2023

Purpose

Managing the growing word-of-mouth (WOM) of brand fans has become a new challenge for companies in the fan economy era. The purpose of this paper is to examine the effect of language intensity of brand fan WOM on customers' willingness to adopt WOM based on psychological resistance theory and to reveal the underlying mechanism of this process.

Design/methodology/approach

A research model was developed to test the proposed hypotheses. Two experiments were conducted on an online platform using data from 708 participants. The independent samples t-test and analysis of variance were used to analyze the data.

Findings

The results show that, in the context of WOM among brand fans, high-intensity language leads to a lower willingness to adopt than low-intensity language and threats to freedom mediate this effect. Moreover, the restoration postscript moderates the effect of language intensity on threats to freedom and customers' willingness to adopt WOM.

Originality/value

Unlike previous studies that focused on electronic word-of-mouth (eWOM) language content, this paper focuses on language intensity to reveal the psychological process of customers' willingness to adopt brand fan WOM. The findings not only enrich the research related to the language effect in eWOM, but also deepen the understanding of the influence effect on brand fan WOM, providing effective guidance for brands to manage fan WOM.
Feasibility study of eigenmode propagation through 2D models of vegetation
Authors: Csernyava Oliver , Pavo Jozsef , Badics Zsolt
Published: September 2023

Purpose

This study aims to model and investigate low-loss wave-propagation modes across random media. The objective is to achieve better channel properties for applying radio links through random vegetation (e.g. forest) using a beamforming approach. Thus, obtaining the link between the statistical parameters of the media and the channel properties.

Design/methodology/approach

A beamforming approach is used to obtain low-loss propagation across random media constructed of long cylinders, i.e. a simplified two dimensional (2D) model of agroforests. The statistical properties of the eigenmode radio wave propagation are studied following a Monte Carlo method. An error quantity is defined to represent the robustness of an eigenmode, and it is shown that it follows a known Lognormal statistical distribution, thereby providing a base for further statistical investigations.

Findings

In this study, it is shown that radio wave propagation eigenmodes exist based on a mathematical model. The algorithm presented can find such modes of propagation that are less affected by the statistical variation of the media than the regular beams used in radio wave communication techniques. It is illustrated that a sufficiently chosen eigenmode waveform is not significantly perturbed by the natural variation of the tree trunk diameters.

Originality/value

As a new approach to obtain low-loss propagation in random media at microwave frequencies, the presented mathematical model can calculate scattering-free wave-propagation eigenmodes. A robustness quantity is defined for a specific eigenmode, considering a 2D simplified statistical forest example. This new robustness quantity is useful for performing computationally low-cost optimization problems to find eigenmodes for more complex vegetation models.
Comparing security perceptions and relationship configurations of mobile device modders and non-modders
Authors: Goode Sigi , Riaz Amir
Published: September 2023

Purpose

It is becoming easier for end-users to modify their information system, sometimes against the wishes of management or the original manufacturer. In the mobile device context, “modding”, “jailbreaking” or “rooting” allows a mobile phone user to select operating software and network providers other than those mandated by the original provider. Prior studies have theorised that modders and non-modders possess different perspectives on the relationship between them and their device provider. However, these differences have not been empirically demonstrated in prior work. This paper aims to test theoretical pathways to explain the behavioural relationship effects of security within the modding context.

Design/methodology/approach

This study models four relationship conceptualisations from prior research. The study tests this model using a survey of 464 mobile device users to compare the user attitudes of modders and non-modders.

Findings

Modder and non-modder relationships differ. Both groups value security, but in different ways: modder relationships are governed by satisfaction and commitment, while non-modder relationships are governed more by trust.

Originality/value

To the best of the authors’ knowledge, this is the first study to empirically demonstrate the relationship differences between IS modifiers and non-modifiers. Most published work has focused on IS that are unmodified. Incorporating device modification may improve behavioural understanding of end-users.
Indoor environmental quality and energy use intensity: an empirical post-occupancy evaluation test of on-campus university student housing in Ghana
Authors: Appau Williams Miller , Attakora-Amaniampong Elvis , Anugwo Iruka Chijindu
Published: September 2023

Purpose

To significantly adopt and improve indoor energy efficiency in building infrastructure in developing countries can be a challenging venture. Thus, this study aimed to assess the satisfaction of indoor environmental quality and its effect on energy use intensity and efficient among student housing.

Design/methodology/approach

The study is quantitative and hinged on the contrast theory. A survey of 1,078 student residents living in purpose-built student housing was contacted. Using Post-Occupancy Evaluation and Multiple Linear Regression, critical variables such as thermal comfort, visual comfort and indoor air quality and 21 indicators were assessed. Data on annual energy consumption and total square metre of the indoor area were utilised to assess energy use intensity.

Findings

The study found a direct relationship between satisfaction with indoor environmental quality and energy use intensity. The study showed that students were more satisfied with thermal comfort conditions than visual and indoor air quality. Overall, these indicators contributed to 75.9% kWh/m2 minimum and 43.2% kWh/m2 maximum energy use intensity in student housing in Ghana. High occupancy and small useable space in student housing resulted in high energy use intensity.

Practical implications

Inclusions of sustainable designs and installation of smart mechanical systems are feedback to student housing designers. Again, adaptation to retrofitting ideas can facilitate energy efficiency in the current state of student housing in Ghana.

Originality/value

Earlier studies have argued for and against the satisfaction of indoor environmental quality in student housing. However, these studies have neglected to examine the impact on energy use intensity. This is novel because the assessment of energy use intensity in this study has a positive influence on active design incorporation among student housing.
Nursing students’ experiences of learning practical gerontological nursing skills through online media during COVID-19 pandemic: a qualitative study
Authors: Niemtest Jaturada Jariyarattanakul , Tabootwong Watchara , Jullamate Pornchai
Published: September 2023

Purpose

This study aims to explain the experiences of nursing students while they practiced gerontological nursing through online media during the COVID-19 pandemic.

Design/methodology/approach

Purposive sampling was used to select 20 third-year nursing students. Semi-structured face-to-face interviews were conducted with participants. The collected data were analyzed using the thematic analysis method to identify recurring themes and patterns.

Findings

Four themes emerged from the interviews, including improved practical skills, the impact of online learning, receiving support from close individuals and the need for support. Participants provided specific examples of how they improved their skills through online learning and described the importance of receiving support from those close to them during this challenging time.

Originality/value

Online media is essential for teaching nursing students during the COVID-19 pandemic. This is the main reason for teaching nursing students during times of restricted access to clinical settings. This research provides insights into the challenges and benefits associated with using digital platforms to teach gerontological practice for nursing students.
RAD140 (Testolone) negatively impacts skeletal muscle adaptation, frailty status and mortality risk in female mice
Authors: Brown Austin M. , Ganjayi Muni Swamy , Baumann Cory W.
Published: September 2023

RAD140 is a selective androgen receptor modulator that produces anabolic effects within skeletal muscle. Thus, RAD140 may be effective at treating sarcopenia. No long‐term studies have investigated how RAD140 influences strength in ageing muscle. This study aimed to determine how 10 weeks of RAD140 supplementation impacts strength, recovery from exercise, and overall health in ageing mice. Young and adult females were assigned to receive RAD140 (5 mg/kg) or a control solution. Dorsiflexor muscles were exposed to repeated bouts of eccentric contractions, and torque was measured before and after each bout. Adaptive potential and strength gains were calculated to assess the efficacy of RAD140 in muscle, while frailty status and mortality risk were used to measure health span. Supplementation of RAD140 increased frailty status and mortality risk in the young and adult treated groups compared to the controls (p ≤ 0.042). RAD140 decreased adaptive potential in young (p = 0.040) but not adult mice (p = 0.688). Torque did not differ between groups after 2–3 weeks of recovery (p ≥ 0.135). In conclusion, long‐term RAD140 supplementation reduced indices of overall health and failed to improve strength in female mice, suggesting that RAD140 (at a 5mg/kg dosage) may be more detrimental than beneficial in delaying or preventing sarcopenia.
Physicochemical quality characteristics of foremilk and hindmilk from native and crossbred dairy goats in a semi‐intensive production system
Authors: Erduran Hakan
Published: September 2023

The focus of this study was to investigate how the relative levels of physicochemical compositions in foremilk and hindmilk change during lactation and how they differed in relation to environmental factors and the offspring and maternal factors (including genotype, parity, offspring sex, birth type, flock, and year) that might influence these changes. The effects of these compositional changes on functional and health during lactation were then assessed. In conclusion, the effects of environmental factors on the physicochemical components of foremilk and hindmilk varied throughout lactation, and it is highly likely that these changes reflect the changing requirements of the mother and the growing offspring.
“Like aspirin for arthritis”: A qualitative study of conditional cyber‐deterrence associated with police crackdowns on the dark web
Authors: Décary‐Hétu David , Faubert Camille , Chopin Julien , Malm Aili , Ratcliffe Jerry , Dupont Benoît
Published: September 2023

Research summary

Crackdowns are law enforcement strategies based on the principles of deterrence theory, which stipulates that offenders are rational actors who will refrain from crime if perceived risks are higher than perceived benefits. Studies have shown that the effects of police street drug crackdowns are mostly short termed and followed by considerable displacement. In the early 2010s, an important part of illicit drug trades moved online to cryptomarkets, and law enforcement agencies have responded by engaging in online drug crackdowns. In this study, we focus on the perceptions of dark web users in order to determine, from a qualitative “data‐driven” perspective, whether police online crackdowns may have a cyber‐deterrent effect by analyzing 1796 forum posts. Our results show that these events trigger psychological and practical consequences that participants claim to have a conditional, although minor, deterrent effect. In the majority of cases, dark web users claimed to engage in several forms of spatial and tactical displacement.

Policy implications

Our study suggests that police crackdowns on the dark web have limited, short‐term effectiveness in curbing illicit activities. It proposes that innovative policing approaches such as problem‐oriented policing and “pulling levers/focused deterrence” strategies, which involve identifying key actors and engaging with them, be potentially extended to the dark web. While this approach is promising, it emphasizes the need for further research to assess its efficacy in the online realm, as it is a largely uncharted territory for law enforcement.
Chemical and physical properties of winter squash and their correlation with liking of their sensory attributes
Authors: Moreno Skylar R. , Sims Charles A. , Odabasi Asli , Simonne Amarat , Gao Zhifeng , Chase Carlene A. , Meru Geoffrey , MacIntosh Andrew J.
Published: September 2023

Cucurbita moschata, commonly known as squash or pumpkin, is a member of the Cucurbitaceae family originating from Central America. This species is regarded as heat tolerant and disease resistant and is commonly used in breeding programs. Calabaza (wintersquash) is an emerging market type of C. moschata with increasing popularity in the United States; however, limited research has been conducted to understand how sensory qualities influence consumers’ acceptability and willingness to pay (price). This study compared the sensory perception of C. moschata accessions grown in the continental southeastern United States with their physical and chemical properties using squash prepared from fresh and frozen states. The eight accessions investigated included five hybrids of calabaza from the University of Florida (University of Florida Tropical Pumpkin #), two commercial cultivars of calabaza (La Estrella and Soler), and one butternut squash cultivar (Waltham). The evaluation of fresh calabaza revealed significant differences in consumer preference among cultivars in addition to correlations with sensory attributes. UFTP8 and UFTP24 received the highest ratings, whereas UFTP38 and ‘La Estrella’ were rated lowest. Interestingly, the evaluation of frozen calabaza revealed UFTP8 and ‘Waltham’ Butternut squash as the highest in ranking, while UFTP38 and ‘La Estrella’ retained the lowest ranking. Consumer ratings of fresh samples revealed positive correlations between overall liking, sweetness liking, and texture liking with willingness to pay and soluble solids content (SSC). For calabaza intended for the frozen market, the color, hardness, and SSC were identified as the most significant parameters impacting willingness to pay. These results show how quality attributes can play a crucial role in consumers perception of quality and significantly influence their reported willingness to pay.

Practical Application

Producers and breeders can use positively correlated attributes as indicators of overall liking and to determine pricing for C. moschata products.
Risk factors for ventilator‐associated lower respiratory tract infection in COVID‐19, a retrospective multicenter cohort study in Sweden
Authors: Forsberg Gustaf , Taxbro Knut , Elander Louise , Hanberger Håkan , Berg Sören , Idh Jonna , Berkius Johan , Ekman Andreas , Hammarskjöld Fredrik , Niward Katarina , Balkhed Åse Östholm
Published: September 2023

Background

Ventilator‐associated lower respiratory tract infections (VA‐LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA‐LRTI have been reported among COVID‐19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA‐LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID‐19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA‐LTRI on morbidity and mortality.

Methods

We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID‐19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA‐LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA‐LRTI.

Results

Of a total of 536 included patients, 153 (28.5%) developed VA‐LRTI. Incidence rate of first VA‐LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA‐LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA‐LRTI had fewer ventilator‐free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds‐ratio (aOR) for first VA‐LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31–5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14–3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03–1.07]). Few multidrug‐resistant pathogens were identified. Incidence of VA‐LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves.

Conclusion

We report a high incidence of culture‐verified VA‐LRTI in a cohort of critically ill COVID‐19 patients from the first three pandemic waves. VA‐LRTI was associated with increased morbidity but not 30‐, 60‐, or 90‐day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA‐LRTI.
Risk of suicidal behavior as a function of alcohol use disorder typologies: A Swedish population‐based study
Authors: Lannoy Séverine , Ohlsson Henrik , Kendler Kenneth S. , Stephenson Mallory , Sundquist Jan , Sundquist Kristina , Edwards Alexis C.
Published: September 2023

Background and aims

Alcohol use disorder (AUD) is one of the strongest predictors of suicidal behavior. Here, we measured risk of suicide attempt and death as a function of AUD typologies.

Design

We used AUD typologies from previous latent class analysis: (i) externalizing subtype (characterized by externalizing symptomatology and early age of onset; individuals in this group have lower education and higher familial/social difficulties); (ii) subtype described by minimal psychopathology; and (iii) internalizing subtype (characterized by internalizing symptomatology and later age of onset; individuals in this group have higher education). We used class membership to predict distal outcomes (attempt and death) and performed regressions to evaluate whether differences in suicidal behavior were explained by the group characteristics (sex, age of onset, number and type of AUD registrations, familial/genetic risk for AUD, externalizing and internalizing behaviors, socio‐economic indicators, marital status and childhood family status). We also evaluated the effect of suicide attempt prior to AUD.

Setting and participants

Based on longitudinal Swedish registry data, we included 217 074 individuals with AUD born 1950–80.

Measurements

Suicide attempts were identified using medical registers and deaths using the mortality register.

Findings

Individuals with the externalizing subtype had higher risks of suicidal behavior than other groups [attempt: externalizing versus minimal psychopathology: odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.35, 1.35; externalizing versus internalizing: OR = 1.47, 95% CI = 1.46, 1.48; death: externalizing versus minimal psychopathology: OR = 1.57, 95% CI = 1.57, 1.58; externalizing versus internalizing: OR = 1.99, 95% CI = 1.93, 2.06]. Individuals with minimal psychopathology had higher risks than those with internalizing symptomatology (attempt: OR = 1.09, 95% CI = 1.08, 1.10, death: OR = 1.26, 95% CI = 1.23, 1.30). These differences were explained by age at registration and were related to the number of registrations, sex, education, family disruption and suicide attempt prior to AUD.

Conclusions

Among people in Sweden, considering alcohol use disorder (AUD) heterogeneity appears to be a meaningful way to evaluate suicide risk. The highest risk of suicide attempt and death occurs in the externalizing subtype of AUD, followed by the minimal psychopathology subtype, and then the internalizing subtype.
Evidence for the role of multidisciplinary team care in people with pelvic pain and endometriosis: A systematic review
Authors: Fang Qing Yi , Campbell Nikki , Mooney Samantha S. , Holdsworth‐Carson Sarah J. , Tyson Kate
Published: September 2023

Background

Endometriosis is a chronic, inflammatory condition characterised by the presence of endometrial‐like tissue outside the uterine cavity. Given the multi‐system nature of the disease and the potential for significant negative impact on quality of life, there has been a long‐standing recognition of the need for multidisciplinary care for people with endometriosis. However, there is paucity to the data supporting this approach, and much of the evidence is anecdotal.

Aim

This systematic review aims to describe recent evidence‐based models and patient‐centred perspectives of multidisciplinary care for endometriosis, to improve understanding of the role of an integrated, multidisciplinary team in effectively addressing patients' care needs.

Materials and Methods

PubMed, Medline, Embase and Web of Science were searched for relevant articles published between 1 January 2010 to 7 July 2022.

Results

Nineteen studies met the inclusion and exclusion criteria and pinpointed a multidisciplinary team consisting of gynaecologists, pain specialists, nurses, physiotherapists, psychologists, sex therapists, nutritionists, complementary medicine practitioners, and social workers to be most commonly utilised in holistically managing people with pelvic pain and endometriosis. Furthermore, patient perspectives on care highlighted the need for reliable information, respect and validation of experiences or preferences, discussion of long‐term treatment plans and social and emotional supports.

Conclusion

The trend for multidisciplinary team care for people with endometriosis is growing. Further consumer‐driven clinical studies and outcome evaluations need to be conducted to determine the effect of multidisciplinary care on improvements to quality of life for people living with endometriosis and or pelvic pain.
Pharmacokinetics, pharmacodynamics and safety of the novel C‐X‐C chemokine receptor 3 antagonist ACT‐777991: Results from the first‐in‐human study in healthy adults
Authors: Boof Marie‐Laure , Géhin Martine , Voors‐Pette Christine , Hsin Chih‐Hsuan , Sippel Virginie , Strasser Daniel S. , Dingemanse Jasper
Published: September 2023

Aims

The C‐X‐C chemokine receptor 3 (CXCR3) axis is highly upregulated in the tissue of patients with type 1 diabetes. Antagonizing CXCR3 may reduce the migration of CXCR3‐expressing cells to the pancreas. The pharmacokinetics (PKs), target engagement (TE) (inhibition of CXCR3 internalization) and safety of single‐ and multiple‐ascending doses (SADs and MADs) of ACT‐777991, a novel orally available potent CXCR3 antagonist, were assessed in a double‐blind, randomized, placebo‐controlled phase 1 study.

Methods

Doses up to 100 mg (SAD part) and 40 mg twice daily (MAD part) were investigated in a total of 70 male and female healthy participants. Food effect was integrated as an SAD subpart. PK, TE, safety and tolerability data were collected up to 4 days after (last) dosing.

Results

In both SAD and MAD parts, ACT‐777991 was rapidly absorbed with a time to reach maximum concentration between 0.5 and 1.5 h post dose, followed by a biphasic disposition with a terminal half‐life between 9.7 and 10.3 h. Increase in exposure and maximum concentration of ACT‐777991 were dose‐proportional. Steady state was reached after 48 h with minimal accumulation. The rate but not the extent of absorption was modified by food intake. A dose‐dependent TE was demonstrated in both SAD and MAD parts. ACT‐777991 was well tolerated. Neither a treatment‐related pattern nor a dose‐response relationship was determined for adverse events or any safety variable. No QT prolongation liability of regulatory concern was detected.

Conclusions

In this first‐in‐human study, ACT‐777991 showed good tolerability for all doses tested and a PK and TE profile suitable for further clinical development.
How did corporate responses to the Covid‐19 pandemic correspond with CSR?
Authors: Martinez Fabien , Figge Frank , Castellano Sylvaine , Chakraborty Atreya , Silva‐Gao Lucia
Published: September 2023

This editorial of the special issue addresses the question of whether/how responses to the Covid‐19 pandemic corresponded with authentic CSR. The literature on CSR has tended to endorse a business‐centric perspective and its inherent focus on the search for alignments between CSR activities and the economic/financial interests of the firm. The Covid‐19 pandemic has put this perspective to the test, pushing many companies to engage in distinctively more genuine and authentic CSR and/or demonstrating the importance of prior CSR engagement in facilitating crisis management. The papers included in the special issue appear to converge on the idea that firms combining evidence of both pre‐crisis engagement in CSR and strong CSR performance during the crisis (demonstrated through the deployment of various CSR assets and resources, including certified reporting, social marketing, individual engagement, resilience, legitimacy, trust) have coped better. This provides interested researchers with an opportunity to appreciate the value of CSR during a crisis.
Design Innovation in Nonprofits: A Need for New Design Strategies
Authors: Borra Luisella , Boult John
Published: September 2023

Nonprofits have been slow to welcome design into their organizations. However, nonprofits operate in the same fast‐paced environment as do for‐profit companies, and design can be just as helpful for them in plotting a new and improved course toward more aid for the recipients of their generosity.

Nonprofits are slowly discovering the innovation benefits of design.
Prognostic value of early electrographic biomarkers of epileptogenesis in high‐risk ischaemic stroke patients
Authors: Tatillo Chiara , Legros Benjamin , Depondt Chantal , Rikir Estelle , Naeije Gilles , Jodaïtis Lise , Ligot Noémie , Gaspard Nicolas
Published: September 2023

Background and purpose

Post‐stroke epilepsy (PSE) is frequent. Better prediction of PSE would enable individualized management and improve trial design for epilepsy prevention. The aim was to assess the complementary value of continuous electroencephalography (EEG) data during the acute phase compared with clinical risk factors currently used to predict PSE.

Methods

A prospective cohort of 81 patients with ischaemic stroke who received early continuous EEG monitoring was studied to assess the association of early EEG seizures, other highly epileptogenic rhythmic and periodic patterns, and regional attenuation without delta (RAWOD, an EEG pattern of stroke severity) with PSE. Clinical risk factors were investigated using the SeLECT (stroke severity; large‐artery atherosclerosis; early clinical seizures; cortical involvement; territory of middle cerebral artery) scores.

Results

Twelve (15%) patients developed PSE. The presence of any of the investigated patterns was associated with a risk of epilepsy of 46%, with a sensitivity and specificity of 83% and 78%. The association remained significant after adjusting for the SeLECT score (odds ratio 18.8, interquartile range 3.8–72.7).

Conclusions

It was found that highly epileptogenic rhythmic and periodic patterns and RAWOD were associated with the development of PSE and complemented clinical risk factors. These findings indicate that continuous EEG provides useful information to determine patients at higher risk of developing PSE and could help individualize care.
Rapid erosion along Holderness coast of East Yorkshire, UK and rising eustatic sea levels driven by climate change
Authors: Nowell David A. G.
Published: September 2023

Following the end of the last ice age, decelerating global post‐glacial sea level rises submerged the southern North Sea, and along this coast, 63 km of soft glacial deposits are still being rapidly washed away. The collapse of the massive ice sheets covering Britain, Ireland and Fennoscandia was a complex process, with warming after 14.7 ka. Limited glaciation then returned during the Loch Lomond Stadial at the end of the Pleistocene, Doggerland, connecting Britain with the continent, was slowly immersed, becoming a shrinking island which was rapidly submerged after 8 ka. This coincided with the Storegga tsunami which hit what remained of Doggerland’s shores and along the coasts of Scotland and Northumberland. Since then, the sea has risen by around 27.5 m. Now it is clear eustatic increases in global sea levels are starting to accelerate once again, we must start adjusting to this reality in the way we manage our coastal infrastructure and try to understand more about how this interacts with naturally dynamic shorelines.
Punished and banished: Non‐citizen women's experiences in a Danish prison
Authors: Damsa Dorina
Published: September 2023

The Nordics have employed discourses of gender equality and women's rights and a welfare‐oriented approach to punishment as integral parts of inclusive welfare states and their ‘goodness’. Drawing on ethnographic fieldwork with non‐citizen women at Vestre Prison in Denmark, this article suggests that the will to punish and banish prevails over the state's commitment to women's rights and protection. Rather than being an inherent feature of incarceration, the pain experienced by non‐citizen women in prison is a ‘political statement’ (Bosworth, 2023). Employing precarisation, incarceration and deportation to govern unwanted non‐citizens and (re)produce the borders of membership, the Danish state also reproduces the conditions for gendered harm. Bordered penality, this article concludes, is gendered.
Photodynamic therapy adjuvant to non‐surgical periodontal therapy: Systematic review of randomized clinical trials
Authors: Souza Daniel Adrian Silva , de Lima Dantas Juliana Borges , Souto Camila Silva , Mendonça Dina Marques , Oliveira Tiago José Silva , dos Santos Vianna Néri Júlia
Published: September 2023

Objectives

To systematically evaluate randomised controlled trials (RCTs) on whether adjuvant application of antimicrobial photodynamic therapy (aPDT) through the technique of irradiation in the external region of the periodontal pocket with optic‐fibre tip offers benefits to scaling and root planning (SRP).

Methods

Five databases were searched by two independent reviewers according to pre‐specified eligibility criteria up to April 2023. No restrictions regarding date of publication, language and minimum follow‐up period were imposed. The Cochrane Collaboration's Risk of Bias tool (RoB 2.0) was used for quality appraisal and Grading of Recommendations, Assessment, Development and Evaluation for assessing the certainty of evidence.

Results

A total of 1388 publications were identified and reviewed for eligibility. Four of them fulfilled the inclusion criteria. The sample consisted of a total of 83 patients with periodontitis. In these, 330 periodontal sites were evaluated. The clinical findings of the majority of the included studies demonstrated that patients who received the association of aPDT + RAR with the protocol evaluated here, obtained clinical results similar to patients who received only the SRP alone. In none of the evaluated RCTs, clinical advantages were observed that would categorise this aPDT protocol as superior to conventional treatment.

Conclusion

Applying aPDT after SRP with external irradiation of the periodontal pocket does not seem to result in any clinical benefit compared to the use of SRP alone in patients with periodontitis.
A case–control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S‐100 and toluidine blue stain and its therapeutic implications
Authors: Agrawal Diksha , Sardana Kabir , Mathachan Sinu Rose , Bhardwaj Minakshi , Ahuja Arvind , Jain Swasti , Panesar Sanjeet
Published: September 2023

Background

The pathogenesis of prurigo nodularis (PN) is considered to be multifactorial, with numerous cells and cytokines confabulating to produce an aberrant immune response.

Methods

A cross‐sectional observational study was done in cases of untreated primary prurigo nodularis cases with histopathological assessment in 49 cases from lesional and nonlesional skin with assessment of epidermal and dermal changes, dermal infiltrate, S‐100 and toluidine blue staining to assess the expression of nerve and mast cells.

Results

The most common histological changes seen in lesional skin were hyperkeratosis (98%), irregular hyperplasia (69.4%), hypergranulosis (69.4%), subepidermal clefting (6%), vertical collagen bundles (51.0%), and dermal fibrosis (48.9%). Chronic inflammatory infiltrate was seen in all cases (100%) predominantly of lymphocytes (100%) followed by eosinophils (18.4%), plasma cells (8.2%), and neutrophils (2.0%). There was a marked increase in the expression of S‐100 (6.92 ± 3.40 vs. 3.94 ± 2.15, P < 0.001) and toluidine blue (4.99 ± 4.47 vs. 1.22 ± 1.28, P < 0.001) in the lesional skin as compared to the nonlesional skin.

Conclusion

We can infer that the epidermal and dermal pathology in PN is related to the infiltrate of lymphocytes, mast cells, and neural hyperplasia which perpetuate the pathogenesis by triggering the itch‐inflammation cycle. Thus, apart from immunosuppressive agents that target lymphocytes and their cytokines, therapy targeted at mast cells and neural proliferation may be needed to treat prurigo nodularis.
Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell‐mediated immune surveillance
Authors: Afolabi Lukman O. , Bi Jiacheng , Chen Liang , Yang Xiaolu , Wan Xiaochun
Published: September 2023

Tumorigenesis entails circumventing cell‐intrinsic regulatory mechanisms while avoiding extrinsic immune surveillance and other host defence systems. Nevertheless, how tumour cells' ability to eliminate misfolded proteins affects immune surveillance remains poorly understood. In this study, we find that overexpression of murine tripartite motif‐containing protein 30a (TRIM30a) sensitises tumour cells to natural killer (NK) cells‐mediated cytolysis. TRIM30a has no effect on tumour cell proliferation or apoptosis in vitro. However, TRIM30a‐overexpressing tumour cells grow substantially slower than control tumour cells in immune‐competent mice but not in NK cell‐depleted mice. [Correction added on 04 October 2023, after first online publication: ‘NK‐depleted’ has been changed to ‘NK cell‐depleted’ in the preceding sentence.] Mechanistically, TRIM30a overexpression impedes the clearance of misfolded proteins and increases the production of reactive oxygen species induced by proteotoxic stress, implying that TRIM30a impairs protein quality control (PQC) systems in tumour cells. Furthermore, TRIM30a reduces expression of genes encoding proteasome subunits and antioxidant proteins. Our study demonstrates that TRIM30a is a potential tumour suppressor and immune modulator that promotes tumour cytolysis by NK cells, and suggests that an enhanced PQC and antioxidant capacity is an integral part of the immune escape mechanism during tumorigenesis.
The Comorbidity of Post‐traumatic Stress Disorder and Suicidality in Vietnam Veterans
Authors: Kramer Teresa L. , Lindy Jacob D. , Green Bonnie L. , Grace Mary C. , Leonard Anthony C.
Published: September 2023

Vietnam veterans (N = 232) recruited from three sources were assessed for suicidal thinking and behaviors, and symptoms of posttraumatic stress disorder (PTSD) and depression. Findings support the notion that suicidal thoughts are prevalent in this group, with veterans in psychotherapy reporting a greater likelihood of such symptoms (82.6%) than veterans in the community (35.7%) or those seeking assistance through a veteran's outreach center (66.7%). Thoughts of ending one's life and a previous suicide attempt were significantly correlated with a diagnosis of PTSD (r = .53, p < .001; and r = .33, p < .001, respectively). Veterans with a diagnosis of PTSD and depression or dysthymia were also more likely to report suicidal thinking and behaviors than veterans with only one of the diagnoses.
Protective Factors for Suicidal Black Females
Authors: Nisbet Paul A.
Published: September 2023

The purpose of this study is to evaluate the extent to which a model of social support may help explain the low suicide rate of Black females. The data are taken from the National Institute of Mental Health's Epidemiologic Catchment Area Study 1980–1985 (United States). The LISREL model examines the direct and indirect effects of the background characteristics on attempted suicide as mediated by emotional state. Results indicate evidence that for Black and White males and females, finding emotional and psychological support in friends and family members helps to safeguard against suicide. The most substantial finding is that for all race/sex categories, seeking support from friendship and familial resources is negatively related to attempted suicide, whereas seeking support from professional resources is associated with an increase in the likelihood of a suicide attempt. This increased likelihood of attempted suicide may be reflecting populations members' resistance to seeking professional help until their emotional state has severely deteriorated.
Fathers' experiences of living with a child with a progressive life‐limiting condition without curative treatment options: A qualitative systematic review
Authors: Sjuls Marianne , Ludvigsen Mette Spliid , Robstad Nastasja , Fegran Liv
Published: September 2023

Aim

To systematically review and synthesize findings across qualitative primary studies about fathers' experiences of living with a child with a progressive life‐limiting condition without curative treatment options (C3 conditions).

Design

Systematic review and metasynthesis.

Methods

Sandelowski and Barosso's qualitative research methodology guided this review and metasynthesis. A modification of Ricoeur's interpretation theory, described by Lindseth and Norberg, guided the synthesis of qualitative data. The quality of the studies was evaluated using the Joanna Briggs Institute Checklist for Qualitative Research.

Data Sources

A systematic literature search was conducted on 6 May 2022 and updated on 19 July 2023 on MEDLINE, CINAHL Plus with Full Text, APA PsycInfo and Scopus. Inclusion criteria were English‐written qualitative studies from the year 2000, from which we could extract data on fathers' experiences of living with a child from 0 to 18 years with a progressive life‐limiting condition without curative treatment options.

Results

Seven reports from Western countries contributed to the review. Through structural analysis, we developed the following themes: ‘Being shattered in the perception of fatherhood’, ‘Establishing a new normal’ and ‘Striving to be acknowledged as a part of the caring team’.

Conclusion

Fathers had to establish a new normal, and they experienced anticipatory mourning, role conflicts and feeling sidelined in healthcare settings when living with a child with a C3 condition. An important issue for further research on paediatric palliative care (PPC) should be to include fathers in the research sample and report separately on fathers' or mothers' experiences instead of parents' experiences.

Impact

The findings will be of interest to healthcare personnel and multidisciplinary teams working within PPC, as they give insight into fathers' experiences and suggest interventions to increase healthcare personnel's involvement with fathers, such as telemedicine.

Reporting Method

Following EQUATOR guidelines, the study was reported according to the enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) framework.

Patient or Public Contribution

No patient or Public Contribution.
Tangible digital collaborative storytelling in adolescents with intellectual disability and neurodevelopmental disorders
Authors: Alonso‐Campuzano Cristina , Iandolo Giuseppe , Filosofi Fabio , Tardivo Angela , Sosa‐González Noelia , Pasqualotto Angela , Venuti Paola
Published: September 2023

Background

Collaborative storytelling can be a helpful tool to promote cognitive and social skills in adolescents with neurodevelopmental disorders.

Aims

The current study aimed to explore the benefits of collaborative storytelling using traditional (TST), digital (DST), and tangible digital (TDST) methodologies.

Materials and Methods

Fourteen Spanish students with mild to moderate intellectual disability and other neurodevelopmental comorbid disorders participated in collaborative storytelling sessions in the classroom, following an experimental, mixed, and cross‐sectional design. The study comprised three individual assessments of narrative skills and eight collaborative storytelling sessions using different storytelling methodologies. Individual and collaborative stories were videotaped, transcribed verbatim, and analysed for formal and content characteristics. Behaviours and interactions during the collaborative storytelling were analysed for each group and session.

Results

The results show a positive effect of collaboration on students' stories, compared to individual performance, regardless of the methodology used.

Conclusion

Collaboration, technological device handling, and shared storytelling did not present a barrier for the participants.