bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling corporate social responsibility and organizational attractiveness: the underlying mechanism of organizational trust
Authors: Chowdhury Md Sohel , Moniruzzaman H.M. , Lipy Nusrat Sharmin , Kang Dae-seok
Published: December 2023

Purpose

Drawing on signaling and social identity theories, the main objective of this paper is to suggest and validate a research framework to investigate the association of corporate social responsibility (CSR) perceptions with organizational attractiveness by uncovering the underlying mechanism of organizational trust.

Design/methodology/approach

By conducting regression analysis, the study hypotheses were tested with the data collected from a snowball convenient sample of 318 potential job seekers.

Findings

The study results revealed that prospective applicants' perceptions about a company's CSR undertakings are significantly associated with their trust in and attraction to the company. Noticeably, organizational trust partially mediated the direct relationship between CSR perceptions and organizational attractiveness.

Research limitations/implications

Based on the study results, some specific theoretical advancements and helpful insights have been highlighted for human resources (HR) practitioners in today's competing organizations. The paper ends by outlining key research drawbacks and directions for possible work in the future.

Originality/value

Despite the plausible underlying role of organizational trust in the link between CSR and organizational attraction, empirical studies of this theoretical phenomenon are still lacking in the context of pre-hire recruitment literature. This may be the first study that identifies organizational trust as a salient psychological factor through which job seekers' CSR perceptions become more instrumental in influencing their attraction to a firm.
Herbaceous species and dry forest species have more acquisitive leaf traits than woody species and wet forest species
Authors: Matsuo Tomonari , van der Sande Masha T. , Amissah Lucy , Dabo Jonathan , Mohammed Abdul Salim , Poorter Lourens
Published: December 2023

Life forms are key to understand the changes in species composition and vegetation types in space and with succession over time. We asked how life forms from dry and wet regions differ in their leaf traits and trait hyperspace (i.e. trait variation) in early tropical forest succession on abandoned agricultural fields.

We compared 324 early successional species from six life forms (herbs, grasses, vines, lianas, shrubs and trees) that occur in the first 5 years of succession on abandoned fields in Ghanaian wet and drought deciduous tropical forests. We measured 12 leaf traits that are important for carbon, water and nutrient use.

A principal component analysis showed that 46% of trait variation is captured by a two‐dimensional spectrum of plant form and function: a leaf economics spectrum underpinning fast‐slow growth strategies, and a leaf size spectrum related to plant size and heat balance, which underlie species sorting along environmental gradients in space and time (during succession). Herbaceous and woody life forms had different leaf economics strategies: herbaceous species had more acquisitive trait values (e.g. higher leaf nutrient concentrations) that increase resource capture and use efficiency whereas woody species had more conservative trait values (e.g. higher leaf mass per area) that increase resource conservation. Regardless of life forms, dry forest species and deciduous species had more acquisitive trait values than wet forest species and evergreen species as they maximize their growth during the shorter growing season. The trait hyperspace was larger for woody life forms especially in wet forests.

Synthesis. Herbaceous species had ‘faster’ leaf economics trait values and, hence, rapid carbon gain, explaining their success earlier in succession. In contrast, woody species had ‘slower’ resource conservation trait values that increase persistence, thus explaining their success later in succession. Deciduous species especially in a dry region had higher leaf nitrogen and phosphorus concentration to attain faster carbon gain to cope with a seasonally harsh environment. The trait hyperspace was generally smaller in the dry forest, as there are more deciduous species, and as a result, there is less variation in leaf lifespan and associated traits.

Read the free Plain Language Summary for this article on the Journal blog.
Association of Medicaid expansion with health insurance, unmet need for medical care and substance use disorder treatment among people who inject drugs in 13 US states
Authors: Cooper Hannah , Beane Stephanie , Yarbrough Courtney , Haardörfer Regine , Ibragimov Umed , Haley Danielle , Linton Sabriya , Beletsky Leo , Landes Sarah , Lewis Rashunda , Peddireddy Snigdha , Sionean Catlainn , Cummings Janet ,   for the NHBS Study Group
Published: December 2023

Background and Aims

Impoverished people who inject drugs (PWID) are at the epicenter of US drug‐related epidemics. Medicaid expansion is designed to reduce cost‐related barriers to care by expanding Medicaid coverage to all US adults living at or below 138% of the federal poverty line. This study aimed to measure whether Medicaid expansion is (1) positively associated with the probability that participants are currently insured; (2) inversely related to the probability of reporting unmet need for medical care due to cost in the past year; and (3) positively associated with the probability that they report receiving substance use disorder (SUD) treatment in the past year, among PWID subsisting at ≤ 138% of the federal poverty line.

Design

A two‐way fixed‐effects model was used to analyze serial cross‐sectional observational data.

Setting

Seventeen metro areas in 13 US states took part in the study.

Participants

Participants were PWID who took part in any of the three waves (2012, 2015, 2018) of data gathered in the Center for Disease Control and Prevention’s National HIV Behavioral Surveillance (NHBS), were aged ≤ 64 years and had incomes ≤ 138% of the federal poverty line. For SUD treatment analyses, the sample was further limited to PWID who used drugs daily, a proxy for SUD.

Measurements

State‐level Medicaid expansion was measured using Kaiser Family Foundation data. Individual‐level self‐report measures were drawn from the NHBS surveys (e.g. health insurance coverage, unmet need for medical care because of its cost, SUD treatment program participation).

Findings

The sample for the insurance and unmet need analyses consisted of 19 946 impoverished PWID across 13 US states and 3 years. Approximately two‐thirds were unhoused in the past year; 41.6% reported annual household incomes < $5000. In multivariable models, expansion was associated with a 19.0 [95% confidence interval (CI) = 9.0, 30.0] percentage‐point increase in the probability of insurance coverage, and a 9.0 (95% CI = −15.0, −0.2) percentage‐point reduction in the probability of unmet need. Expansion was unrelated to SUD treatment among PWID who used daily (n = 17 584).

Conclusions

US Medicaid expansion may curb drug‐related epidemics among impoverished people who inject drugs by increasing health insurance coverage and reducing unmet need for care. Persisting non‐financial barriers may undermine expansion’s impact upon substance use disorder treatment in this sample.
Surgeon reported measures of stress and anxiety prior to and after elective gynecological surgery
Authors: Budden Aaron K. , Song Sophia , Henry Amanda , Wakefield Claire E. , Abbott Jason A.
Published: December 2023

Introduction

Performing surgical procedures is a recognized source of stress for surgeons. Vocational stress is an important contributor to performance, patient care, and burnout with dispositional and environmental factors contributing. Accurately assessing surgeon stress is critical to measuring effectiveness of stress reduction programs. The primary aim was to identify differences between surgeons' self‐reported anticipated stress and anxiety prior to gynecological surgery, compared with their recollection of experienced stress and anxiety during surgery. Secondary aims assessed any differences by level of training, surgical type, and surgeon role.

Material and methods

Attending and resident gynecologists performing routine elective surgeries completed a visual analog scale (VAS) assessing perceived stress and the State–Trait Anxiety Inventory (STAI) prior to and immediately after completing 161 elective surgeries including total laparoscopic hysterectomy, laparoscopic excision of moderate–severe endometriosis, or hysteroscopic myomectomy.

Results

Eight attending gynecologists and nine residents participated. Residents commenced as primary surgeon in 62/90 (69%) procedures. Stress experienced during surgery was greater than anticipated in 92/161 (57%) surgery episodes (mean VAS increase: 3.9; 95% CI: 1.1–6.8, p = 0.009). State anxiety was greater than anticipated in 99/161 (62%) episodes (mean state anxiety increase: 4.4; 95% CI: 3.0–5.8, p < 0.001). Greater preprocedural anticipatory stress and anxiety was observed in residents vs. attending gynecologists (VAS 51.9 vs. 22.8, p < 0.001; state anxiety 38.3 vs. 28.1, p < 0.001) and in primary vs. assistant surgeons (VAS 47.2 vs. 29.9, p < 0.001; state anxiety 36.9 vs. 28.3, p < 0.001). Intraoperative stress and anxiety were greater in primary surgeons (VAS 50.4 vs. 30.5, p < 0.001; anxiety 41.3 vs. 32.5, p < 0.001) and residents (VAS 43.4 vs. 31.7, p < 0.001; anxiety 53.5 vs. 33.7, p < 0.001) compared with assistants and attending gynecologists. Perceived stress and anxiety were positively correlated at both timepoints (r = 0.68, p < 0.001; r = 0.82, p < 0.001).

Conclusions

When asked to reflect on stress experienced during surgery, our data show that stress during surgery is greater than anticipated for many surgical episodes. Self‐reported stress symptoms commence prior to surgery and are more commonly reported by surgeons operating as primary surgeon and by those in training. Future research should focus on determinants of presurgical stress and examine when stressors become inhibitory to performance.
Prevention of obstetric anal sphincter injuries with perineal support and lateral episiotomy: A historical cohort study
Authors: Eggebø Torbjørn M. , Rygh Astrid Betten , von Brandis Phillip , Skjeldestad Finn Egil
Published: December 2023

Introduction

There are many risk factors for obstetric anal sphincter injury (OASIS) and the interaction between these risk factors is complex and understudied. The many observational studies that have shown a reduction of OASIS rates after implementation of perineal support have short follow‐up time. We aimed to study the effect of integration of active perineal support and lateral episiotomy on OASIS rates over a 15‐year period and to study interactions between risk factors known before delivery.

Material and methods

We performed a historical cohort study over the periods 1999–2006 and 2007–2021 at Stavanger University Hospital, Norway. The main outcome was OASIS rates. Women without a previous cesarean section and a live singleton fetus in cephalic presentation at term were eligible. The department implemented in 2007 the Finnish concept of active perineal protection, which includes support of perineum, control of fetal expulsion, good communication with the mother and observation of perineal stretching. The practice of mediolateral episiotomy was replaced with lateral episiotomy when indicated. We analyzed the OASIS rates in groups with and without episiotomy stratified for delivery mode, fetal position at delivery and for parity, and adjusted for possible confounders (maternal age, gestational age, oxytocin augmentation and epidural analgesia).

Results

We observed a long‐lasting reduction in OASIS rates from 4.9% to 1.9% and an increase in episiotomy rates from 14.4% to 21.8%. Lateral episiotomy was associated with lower OASIS rates in nulliparous women with instrumental vaginal deliveries and occiput anterior (OA) position; 3.4% vs 10.1% (OR 0.31; 95% CI: 0.24–0.40) and 6.1 vs 13.9% (OR 0.40; 95% CI: 0.19–0.82) in women with occiput posterior (OP) position. Lateral episiotomy was also associated with lower OASIS rates in nulliparous women with spontaneous deliveries and OA position; 2.1% vs 3.2% (OR 0.62; 95% CI: 0.49–0.80). The possible confounders had little confounding effects on the risk of OASIS in groups with and without episiotomy.

Conclusions

We observed a long‐lasting reduction in OASIS rates after implementation of preventive procedures. Lateral episiotomy was associated with lower OASIS rates in nulliparous women with an instrumental delivery. Special attention should be paid to deliveries with persistent OP position.
The effect of ability, motivation and opportunity (AMO) on SMEs' innovation performance
Authors: Alkhalaf Taher , Al‐Tabbaa Omar
Published: December 2023

While there is extensive research on SMEs' innovation, limited attention has been given to the specific implications of HRM practices in fostering innovation in this sector. This represents a critical gap, considering the unique challenges faced by SMEs in managing their human resources. Accordingly, in this study, we developed and validated a conceptual model that evaluates the ability of SMEs to enhance their innovation and innovation performance through the adoption of HRM practices that relate to employees' abilities, motivations and opportunities (AMO). Data was collected through a survey of manufacturing SMEs in France. Overall, the findings contribute to the literature by shedding light on the mediating role of innovation between HR‐enhancing practices and innovation performance in SMEs. In addition, the analysis highlights the importance of HRM practices in shaping workforce capabilities and influencing organizational performance. Moreover, it emphasizes the importance of structured HRM practices in attracting and retaining high‐quality human resources, akin to larger companies. These findings have practical implications for SME owners, managers and policymakers seeking to foster innovation and enhance organizational performance in the SME context.
Pharmacokinetics and pharmacodynamics of cannabis‐based medicine in a patient population included in a randomized, placebo‐controlled, clinical trial
Authors: Hansen Julie Schjødtz , Boix Fernando , Hasselstrøm Jørgen Bo , Sørensen Lambert Kristiansen , Kjolby Mads , Gustavsen Stefan , Hansen Rikke Middelhede , Petersen Thor , Sellebjerg Finn , Kasch Helge , Rasmussen Peter Vestergaard , Finnerup Nanna Brix , Sædder Eva Aggerholm , Svendsen Kristina Bacher
Published: December 2023

Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis‐based medicine (CBM) in capsule formulation in patient populations is sparse. In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple sclerosis (MS). Of 134 patients participating in a randomized, double‐blinded, placebo‐controlled, trial, 23 patients with MS (17 female) mean age 52 years (range 21–67) were enrolled in this substudy. They received oral capsules containing Δ9‐tetrahydrocannabinol (THC, n = 4), cannabidiol (CBD, n = 6), a combination (THC&CBD, n = 4), or placebo (n = 9). Maximum doses were 22.5 mg (THC) and 45 mg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultra‐high‐performance liquid chromatography–tandem mass spectrometer after protein precipitation and phospholipid removal. PK parameters were estimated using computerized modeling. The variation in daily dose and PK between individuals was considerable in a steady state, yet comparable with previous reports from healthy controls. Based on a simulation of the best model, the estimated PK parameters (mean) for THC (5 mg) were Cmax 1.21 ng/mL, Tmax 2.68 h, and half‐life 2.75 h, and for CBD (10 mg) were Cmax 2.67 ng/mL, Tmax 0.10 h, and half‐life 4.95 h, respectively. No effect was found on the PD parameters, but the placebo response was considerable. More immediate adverse events were registered in the active treatment groups compared with the placebo group.
Justice metamorphosis: Moving from reactive to proactive strategies to remotely protect families from intimate partner violence
Authors: Davis Alicia , Vandenberg Van Zee Sarah , Geiger Conor
Published: December 2023

The pandemic accelerated the adoption of remote access to courts through e‐filing and virtual hearings. Concurrently, courts experienced an increase in intimate partner violence cases due in part to heightened stress during the pandemic. Virtual technology became crucial for individuals seeking relief from harm when traditional support systems were limited. However, remote proceedings lack the personal connection found in‐person, making it challenging to handle complex cases involving parenting and intimate partner violence. Courts must strike a balance between protecting parents and children from abuse and ensuring due process and appropriate parenting time for the accused party. Some courts have considered the user experience in intimate partner violence and parenting cases, but as remote justice become the norm, it is essential for all courts to evaluate and refine the tools, policies, and procedures put in place during the emergency response to the pandemic to be more proactive in supporting court users. State courts in Kansas, North Carolina, and Arizona are cited as examples for efforts to enhance remote justice efficiency and quality in these cases involving intimate partner violence and parenting. Further research is recommended to explore the challenges and possibilities of using virtual technology in these situations.
A cytochrome P450 gene, LpCYP72A15, confers drought tolerance in perennial ryegrass
Authors: Xing Jing , Yang Yuwei , Zhang Qing , Yin Tingchao , Zhao Ruijie , Hao Guan , Liu Xinbao , Chi Yingjun , Zhang Jing
Published: December 2023

Cytochrome P450s (CYPs) play crucial roles in regulating plant growth, development, and stress tolerance. In this study, a perennial ryegrass (Lolium perenne) CYP gene, LpCYP72A15, was identified as a candidate gene regulating plant osmotic stress tolerance based on a cDNA library screening in the background of yeast ∆hog1 mutant. LpCYP72A15 is localized in the plastids, and its expression was regulated by osmotic stress and ABA treatment. Overexpressing LpCYP72A15 significantly enhanced plant drought tolerance in both Arabidopsis and perennial ryegrass. Under drought stress, the transgenic ryegrass showed significant lower reactive oxygen species (ROS) levels, higher ROS‐scavenging enzymatic activities, and higher soluble sugar contents than the wildtype plants. Transient over‐expressing the gene also enhanced survival rates of ryegrass mesophyll protoplasts under H2O2‐induced oxidative or mannitol‐enforced osmotic stresses. Taken together, LpCYP72A15 confers oxidative‐ and osmotic‐stress tolerances that positively regulates plant drought tolerance in perennial ryegrass.
The relationship between possible, probable, or definite sleep bruxism and sleep quality: A systematic review
Authors: Yanez‐Regonesi Fernanda , Sangalli Linda , Robinson Cayla , de Leeuw Reny
Published: December 2023

It has been suggested that sleep bruxism may interrupt sleep continuity, hence potentially influencing sleep quality. The aim of this study was to systematically review the relationship between possible, probable, and definite sleep bruxism and sleep quality in otherwise healthy individuals. A systematic search on sleep bruxism and sleep quality was performed in seven databases until 19 December 2022. Eligible articles were screened, and quality assessment was performed via the Joanna Briggs Institute Scale. Of 3681 articles screened, 13 were included in this study. Of these, six evaluated the relationship between sleep quality and possible sleep bruxism, three with probable sleep bruxism, and four with definite sleep bruxism. An association between poor sleep quality and sleep bruxism was found among those individuals diagnosed with possible and probable sleep bruxism. However, the studies conducted in individuals with definite sleep bruxism failed to demonstrate any association. With more reliable measures to evaluate sleep bruxism, a relationship between sleep bruxism and sleep quality was not evident.
A Chto Sluchilos'?: Ethnographies of Holding It Together
Authors: Chudakova Tatiana , Hartblay Cassandra , Sidorkina Maria
Published: December 2023

This essay by sociocultural anthropologists of Russia working in the North American academy considers rupture in three ways. First, we review rupture as a theoretical concept that ethnographers have both used and contested in making sense of the end of the Soviet Union, to inform our reading of the present moment. Second, we think about what political and social relationships the war has made speakable and for whom, at a time when the possibilities of free expression in Russia carry novel risks. Anthropologists working with indigenous and ethnic minorities in Russia have long insisted on the country’s internal plurality. Drawing on this scholarship, we discuss the ways in which plurality has been freshly repoliticized in the context of the war in Ukraine, while carrying forward some of the legacies of its Soviet orchestration. Third, we observe that the 2022 invasion of Ukraine marks a rupture for ethnographers in the way we do fieldwork in and of Russia. In response, we call for a scholarly praxis of suturing together multiple scales of analysis, digital and geographic locations and incommensurable perspectives.
COVID‐19 cases correlates with greater acceptance coping in flexible cultures: A cross‐cultural study in 26 countries
Authors: Zhou Xiaoyu , English Alexander Scott , Kulich Steve J. , Zheng Lu ,   Global COVID Project Members
Published: December 2023

The current study examines whether the prevalence of COVID‐19 cases and cultural flexibility correlate to one's use of acceptance coping across 26 cultures. We analyzed data from 7476 participants worldwide at the start of the first outbreak from March 2020 to June 2020. Results showed that cultural flexibility moderated the relationship between COVID‐19 cases and individuals' acceptance coping strategies. Specifically, for cultures with high flexibility, COVID‐19 cases correlated with more acceptance coping; for cultures with low flexibility, COVID‐19 cases correlated with less acceptance coping. This result demonstrates how participants from flexible cultures can coexist with the realistic challenges and suffering faced during this pandemic.
Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS‐CoV‐2 infection and vaccination
Authors: Roubinian Nareg H. , Greene John , Liu Vincent X. , Lee Catherine , Mark Dustin G. , Vinson David R. , Spencer Bryan R. , Bruhn Roberta , Bravo Marjorie , Stone Mars , Custer Brian , Kleinman Steve , Busch Michael P. , Norris Philip J. ,   for the NHLBI Recipient Epidemiology and Donor Evaluation Study‐IV‐P (REDS‐IV)
Published: December 2023

Background

The safety of transfusion of SARS‐CoV‐2 antibodies in high plasma volume blood components to recipients without COVID‐19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS‐CoV‐2 infection and vaccination was associated with changes in outcomes in hospitalized patients without COVID‐19.

Methods

We conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre‐COVID‐19 (3/1/2018–2/29/2020), COVID‐19 pre‐vaccine (3/1/2020–2/28/2021), and COVID‐19 post‐vaccine (3/1/2021–8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Among 21,750 hospitalizations of 18,584 transfusion recipients without COVID‐19, there were 697 post‐transfusion thrombotic events, and oxygen requirements were increased in 1751 hospitalizations. Intensive care unit length of stay (n = 11,683) was 3 days (interquartile range 1–5), hospital mortality occurred in 3223 (14.8%), and 30‐day rehospitalization in 4144 (23.7%). Comparing the pre‐COVID, pre‐vaccine and post‐vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p = .22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p = .41). In parallel, there were no trends across study periods for ICU length of stay (p = .83), adjusted hospital mortality (OR 1.0 [95% CI 0.9–1.0]; p = .36), or 30‐day rehospitalization (p = .29).

Discussion

Transfusion of plasma and platelet blood components collected during the pre‐vaccine and post‐vaccine periods of the COVID‐19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID‐19.
Davemaoite as the mantle mineral with the highest melting temperature
Authors: Yin Kun , Belonoshko Anatoly B. , Li Yonghui , Lu Xiancai
Published: December 2023

Knowledge of high-pressure melting curves of silicate minerals is critical for modeling the thermal-chemical evolution of rocky planets. However, the melting temperature of davemaoite, the third most abundant mineral in Earth’s lower mantle, is still controversial. Here, we investigate the melting curves of two minerals, MgSiO
3
bridgmanite and CaSiO
3
davemaoite, under their stability field in the mantle by performing first-principles molecular dynamics simulations based on the density functional theory. The melting curve of bridgmanite is in excellent agreement with previous studies, confirming a general consensus on its melting temperature. However, we predict a much higher melting curve of davemaoite than almost all previous estimates. Melting temperature of davemaoite at the pressure of core-mantle boundary (~136 gigapascals) is about 7700(150) K, which is approximately 2000 K higher than that of bridgmanite. The ultrarefractory nature of davemaoite is critical to reconsider many models in the deep planetary interior, for instance, solidification of early magma ocean and geodynamical behavior of mantle rocks.
Animal robots in the African wilderness: Lessons learned and outlook for field robotics
Authors: Melo Kamilo , Horvat Tomislav , Ijspeert Auke J.
Published: December 2023

In early 2016, we had the opportunity to test a pair of sprawling posture robots, one designed to mimic a crocodile and another designed to mimic a monitor lizard, along the banks of the Nile River in Uganda, Africa. These robots were developed uniquely for a documentary by the BBC called Spy in the Wild and fell at the intersection of our interests in developing robots to study animals and robots for disaster response and other missions in challenging environments. The documentary required that these robots not only walk and swim in the same harsh, natural environments as the animals that they were modeled on and film up close but also move and even look exactly like the real animals from an aesthetic perspective. This pushed us to take a fundamentally different approach to the design and building of biorobots compared with our typical laboratory-residing robots, in addition to collaborating with sculpting artists to enhance our robots’ aesthetics. The robots needed to be designed on the basis of a systematic study of data on the model specimens, be fabricated rapidly, and be reliable and robust enough to handle what the wild would throw at them. Here, we share the research efforts of this collaboration, the design specifications of the robots’ hardware and software, the lessons learned from testing these robots in the field first hand, and how the eye-opening experience shaped our subsequent work on disaster response robotics and biorobotics for challenging amphibious scenarios.
Pseudorabies virus upregulates low-density lipoprotein receptors to facilitate viral entry
Authors: Ma Ying-Xian , Chai Ya-Jing , Han Ya-Qi , Zhao Shi-Bo , Yang Guo-Yu , Wang Jiang , Ming Sheng-Li , Chu Bei-Bei
Published: December 2023

Pseudorabies virus (PRV) is the causative agent of Aujeszky’s disease in pigs. The low-density lipoprotein receptor (LDLR) is a transcriptional target of the sterol-regulatory element-binding proteins (SREBPs) and participates in the uptake of LDL-derived cholesterol. However, the involvement of LDLR in PRV infection has not been well characterized. We observed an increased expression level of LDLR mRNA in PRV-infected 3D4/21, PK-15, HeLa, RAW264.7, and L929 cells. The LDLR protein level was also upregulated by PRV infection in PK-15 cells and in murine lung and brain. The treatment of cells with the SREBP inhibitor, fatostatin, or with SREBP2-specific small interfering RNA prevented the PRV-induced upregulation of LDLR expression as well as viral protein expression and progeny virus production. This suggested that PRV activated SREBPs to induce LDLR expression. Furthermore, interference in LDLR expression affected PRV proliferation, while LDLR overexpression promoted it. This indicated that LDLR was involved in PRV infection. The study also demonstrated that LDLR participated in PRV invasions. The overexpression of LDLR or inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR and targets it for lysosomal degradation, significantly enhanced PRV attachment and entry. Mechanistically, LDLR interacted with PRV on the plasma membrane, and pretreatment of cells with LDLR antibodies was able to neutralize viral entry. An
in vivo
study indicated that the treatment of mice with the PCSK9 inhibitor SBC-115076 promoted PRV proliferation. The data from the study indicate that PRV hijacks LDLR for viral entry through the activation of SREBPs.

IMPORTANCE

Pseudorabies virus (PRV) is a herpesvirus that primarily manifests as fever, pruritus, and encephalomyelitis in various domestic and wild animals. Owing to its lifelong latent infection characteristics, PRV outbreaks have led to significant financial setbacks in the global pig industry. There is evidence that PRV variant strains can infect humans, thereby crossing the species barrier. Therefore, gaining deeper insights into PRV pathogenesis and developing updated strategies to contain its spread are critical. This study posits that the low-density lipoprotein receptor (LDLR) could be a co-receptor for PRV infection. Hence, strategies targeting LDLR may provide a promising avenue for the development of effective PRV vaccines and therapeutic interventions.
Complete genome of
Flavobacterium pectinovorum
str. ZE23VCel01 obtained through Nanopore Q20+ chemistry
Authors: Serra Moncadas Lucas , Schnellmann Vanessa , Hofer Cyrill , Rain-Franco Angel , Andrei Adrian-Stefan
Published: December 2023

This study reports the complete genome of
Flavobacterium pectinovorum
str. ZE23VCel01 isolated from a freshwater environment. By means of Nanopore Q20+ chemistry, the chromosome was assembled as a circular element with a length of 5.9 Mbp, a GC content of 33.58%, and a coverage of 122×.
Abh, AbrB3, and Spo0A play distinct regulatory roles during polymyxin synthesis in
Paenibacillus polymyxa
SC2
Authors: Cui Yanru , Zhao Dongying , Liu Kai , Mei Xiangui , Sun Shanshan , Du Binghai , Ding Yanqin
Published: December 2023

Polymyxins exhibit antibacterial activity against various gram-negative bacteria. However, the regulatory mechanisms of polymyxin synthesis remain unclear. Here, Abh, AbrB3, and Spo0A of
Paenibacillus polymyxa
SC2 were found to bind to P

pmx

via DNA pull-down and electromagnetic mobility shift assays. Oxford Cup and liquid chromatography-mass spectrometry assays showed that antibacterial activity and polymyxin production increased in the Δ
abh
strain. Overexpression of
abh
and
abrB3
significantly decreased the antibacterial activity and polymyxin production. The transcription of
pmxA
determined via quantitative reverse transcription-PCR supported these results. Moreover, the mutation and complementation of
spo0A
revealed that Spo0A was an activator of polymyxin synthesis. Spo0A could bind to the
abh
promoter to activate
abh
expression. Spo0A could bind to the
abrB3
promoter to inhibit
abrB3
transcription and mitigate the inhibitory effect of AbrB3 on
abh
transcription.

IMPORTANCE

Polymyxins are considered the last line of defense against multidrug-resistant bacteria. The regulatory mechanism of polymyxin synthesis is poorly studied in
Paenibacillus polymyxa
. In this study, we found that Abh and AbrB3 negatively regulated, whereas Spo0A positively regulated polymyxin synthesis in
P. polymyxa
SC2. In addition, a regulatory relationship between Abh, AbrB3, and Spo0A was revealed, which regulate polymyxin synthesis via multiple regulatory mechanisms in
P. polymyxa
.
The governance behaviours: a proposed approach for the alignment of the public and private sectors for better health outcomes
Authors: Clarke David , Appleford Gabrielle , Cocozza Anna , Thabet Aya , Bloom Gerald
Published: December 2023

Health systems are ‘the ensemble of all public and private organisations, institutions and resources mandated to improve, maintain or restore health.’ The private sector forms a major part of healthcare practice in many health systems providing a wide range of health goods and services, with significant growth across low-income and middle-income countries. WHO sees building stronger and more effective health systems through the participation and engagement of all health stakeholders as the pathway to further reducing the burden of disease and meeting health targets and the Sustainable Development Goals. However, there are governance and public policy gaps when it comes to interaction or engagement with the private sector, and therefore, some governments have lost contact with a major area of healthcare practice. As a result, market forces rather than public policy shape private sector activities with follow-on effects for system performance. While the problem is well described, proposed normative solutions are difficult to apply at country level to translate policy intentions into action. In 2020, WHO adopted a strategy report which argued for a major shift in approach to engage the private sector based on the performance of six governance behaviours. These are a practice-based approach to governance and draw on earlier work from Traviset alon health system stewardship subfunctions. This paper elaborates on the governance behaviours and explains their application as a practice approach for strengthening the capacity of governments to work with the private sector to achieve public policy goals.
‘COVID-19 is just another way to die…’: a qualitative longitudinal study of frontline COVID-19 response governance across Syria
Authors: Douedari Yazan , Alhaffar Mervat , Khanshor Ahmad , Alrashid Alhiraki Omar , Marzouk Manar , Howard Natasha
Published: December 2023

Introduction

Governance of COVID-19 responses has been challenging for all countries. Syria has been particularly challenged due to protracted multiparty conflict and debilitated health systems fragmented across different areas of control. To improve response governance, better understanding of frontline response policy implementation across the country is needed. This study thus explored perspectives of COVID-19 response governance among frontline healthcare providers over time and across major areas of control.

Methods

We used a qualitative longitudinal study design, conducting five rounds of remote semistructured interviews in Arabic (ie, approximately eight interviews each in March 2020, July 2020, September 2020, December 2020 and September 2021) with 14 purposively sampled public and private healthcare providers in the three main areas of control (ie, opposition-controlled area, Autonomous Administration-controlled area and al-Assad government-controlled area (GCA)). We conducted integrative thematic analysis in Arabic within and across geography and time.

Results

Almost all participants across all areas and rounds expressed distrust of local health authorities and dissatisfaction with COVID-19 response governance. This was most apparent in initial rounds and in GCA. Response planning was identified as insufficient, non-participatory and non-transparent. Limited infrastructure and resources were the main challenges across time, though anticipated rapid virus spread and health systems’ collapse did not occur and participant optimism increased over time. Public adherence to prevention measures varied—initially weak due to general scepticism, increasing after first cases were confirmed and then fluctuating with case numbers and challenges of insecurity and misinformation. Perceptions of COVID-19 vaccination varied, with low uptake and hesitancy attributed to misinformation, disinformation and disinterest. Suggested improvements to COVID-19 response governance focused on strengthening health systems’ capacity and coordination.

Conclusion

This is a unique longitudinal study of COVID-19 responses. Addressing transparency and misinformation should be a first step to improving public engagement and trust and thus response governance for health emergencies in Syria.
Impact of twice-a-day transcranial direct current stimulation intervention on cognitive function and motor cortex plasticity in patients with Alzheimer’s disease
Authors: Li Xingxing , Chen Lei , Yu Kunqiang , Zhuang Wenhao , Zhu Hui , Xu Wenqiang , Yan Hui , Qi Gangqiao , Zhou Dongsheng , Wu Shaochang
Published: December 2023

Background

Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer’s disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial direct current stimulation (tDCS) in patients still need to be evaluated.

Aims

This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity.

Methods

124 patients with AD were randomly assigned to active tDCS (n=63) or sham tDCS (n=61). The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks (5 days per week, 2 days off). The Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) were used for cognition evaluation at baseline, week 2 and week 6. The cortical plasticity was represented by motor-evoked potential (MEP) measured with an electromyogram.

Results

The results showed that multiple courses of active tDCS can improve the cognitive functions of patients with AD, especially in the memory domain (word recall, recall of test instructions and word recognition). In addition, the damaged MEP level was enhanced following active treatment. In the active tDCS group, the improvements in ADAS-Cog total and subitem (word recall and word recognition) scores were negatively correlated with the enhancement of MEP.

Conclusions

Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity, which warrants mechanistic investigations of the relationship between cognition and plasticity in the future.

Trial registration number

ChiCTR1900021067.
Differential requirements for CD4+ T cells in the efficacy of the anti-PD-1+LAG-3 and anti-PD-1+CTLA-4 combinations in melanoma flank and brain metastasis models
Authors: Phadke Manali S , Li Jiannong , Chen Zhihua , Rodriguez Paulo C , Mandula Jessica K , Karapetyan Lilit , Forsyth Peter A , Chen Y Ann , Smalley Keiran S M
Published: December 2023

Background

Although the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combinations are effective in advanced melanoma, it remains unclear whether their mechanisms of action overlap.

Methods

We used single cell (sc) RNA-seq, flow cytometry and IHC analysis of responding SM1, D4M-UV2 and B16 melanoma flank tumors and SM1 brain metastases to explore the mechanism of action of the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combination. CD4+ and CD8+ T cell depletion, tetramer binding assays and ELISPOT assays were used to demonstrate the unique role of CD4+T cell help in the antitumor effects of the anti-PD-1+LAG-3 combination.

Results

The anti-PD-1+CTLA-4 combination was associated with the infiltration of FOXP3+regulatory CD4+ cells (Tregs), fewer activated CD4+T cells and the accumulation of a subset of IFNγ secreting cytotoxic CD8+T cells, whereas the anti-PD-1+LAG-3 combination led to the accumulation of CD4+T helper cells that expressed CXCR4, TNFSF8, IL21R and a subset of CD8+T cells with reduced expression of cytotoxic markers. T cell depletion studies showed a requirement for CD4+T cells for the anti-PD-1+LAG-3 combination, but not the PD-1-CTLA-4 combination at both flank and brain tumor sites. In anti-PD-1+LAG-3 treated tumors, CD4+T cell depletion was associated with fewer activated (CD69+) CD8+T cells and impaired IFNγ release but, conversely, increased numbers of activated CD8+T cells and IFNγ release in anti-PD-1+CTLA-4 treated tumors.

Conclusions

Together these studies suggest that these two clinically relevant immune checkpoint inhibitor (ICI) combinations have differential effects on CD4+T cell polarization, which in turn, impacted cytotoxic CD8+T cell function. Further insights into the mechanisms of action/resistance of these clinically-relevant ICI combinations will allow therapy to be further personalized.
CXCL10 and Nrf2-upregulated mesenchymal stem cells reinvigorate T lymphocytes for combating glioblastoma
Authors: Mao Jiaji , Li Jianing , Chen Junwei , Wen Qin , Cao Minghui , Zhang Fang , Li Baoxun , Zhang Qinyuan , Wang Zhe , Zhang Jingzhong , Shen Jun
Published: December 2023

Background

Lack of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction have been identified as major contributors to glioblastoma (GBM) immunotherapy resistance. Upregulating CXCL10 in the tumor microenvironment (TME) is a promising immunotherapeutic approach that potentially increases tumor-infiltrating T cells and boosts T-cell activity but is lacking effective delivery methods.

Methods

In this study, mesenchymal stem cells (MSCs) were transduced with a recombinant lentivirus encodingCxcl10,Nrf2(an anti-apoptosis gene), and a ferritin heavy chain (Fth) reporter gene in order to increase their CXCL10 secretion, TME survival, and MRI visibility. Using FTH-MRI guidance, these cells were injected into the tumor periphery of orthotopic GL261 and CT2A GBMs in mice. Combination therapy consisting of CXCL10-Nrf2-FTH-MSC transplantation together with immune checkpoint blockade (ICB) was also performed for CT2A GBMs. Thereafter, in vivo and serial MRI, survival analysis, and histology examinations were conducted to assess the treatments’ efficacy and mechanism.

Results

CXCL10-Nrf2-FTH-MSCs exhibit enhanced T lymphocyte recruitment, oxidative stress tolerance, and iron accumulation. Under in vivo FTH-MRI guidance and monitoring, peritumoral transplantation of CXCL10-Nrf2-FTH-MSCs remarkably inhibited orthotopic GL261 and CT2A tumor growth in C57BL6 mice and prolonged animal survival. While ICB alone demonstrated no therapeutic impact, CXCL10-Nrf2-FTH-MSC transplantation combined with ICB demonstrated an enhanced anticancer effect for CT2A GBMs compared with transplanting it alone. Histology revealed that peritumorally injected CXCL10-Nrf2-FTH-MSCs survived longer in the TME, increased CXCL10 production, and ultimately remodeled the TME by increasing CD8+T cells, interferon-γ+cytotoxic T lymphocytes (CTLs), GzmB+CTLs, and Th1 cells while reducing regulatory T cells (Tregs), exhausted CD8+and exhausted CD4+T cells.

Conclusions

MRI-guided peritumoral administration of CXCL10 and Nrf2-overexpressed MSCs can significantly limit GBM growth by revitalizing T lymphocytes within TME. The combination application of CXCL10-Nrf2-FTH-MSC transplantation and ICB therapy presents a potentially effective approach to treating GBM.
Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion
Authors: Teagle Alexandra Rose , Castro-Sanchez Patricia , Brownlie Rebecca J , Logan Nicola , Kapoor Simran S , Wright David , Salmond Robert J , Zamoyska Rose
Published: December 2023

Background

Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long-term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+T cell antitumor efficacy in ACT. We tested whetherPtpn22KOcytolytic T cells (CTLs) were also more effective thanPtpn22WTCTL in controlling tumors in scenarios that favor T cell exhaustion.

Methods

Tumor control byPtpn22WTandPtpn22KOCTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic restimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins byPtpn22WTandPtpn22KOT cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade onPtpn22KOCTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout.

Results

Despite having improved effector function at the time of transfer,Ptpn22KOCTL became more exhausted thanPtpn22WTCTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced inPtpn22KOcells. Antitumor responses ofPtpn22KOCTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen inPtpn22KOCTL.

Conclusions

This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short-term augmented effector function against the risk of T cell exhaustion in order to achieve longer-term protection.