bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐world efficacy of single‐agent belantamab mafodotin in relapsed systemic AL amyloidosis
Authors: Khwaja Jahanzaib , Bomsztyk Joshua , Atta Maria , Bygrave Ceri , Forbes Adam , Durairaj Senthil , Fernandes Savio , Taylor James , Paterson Pamela , Brearton Gillian , Crawley Charles , Sheehy Oonagh , Brown Rachel , Soutar Richard , Garg Mamta , Rydzewski Andrzej , Jamroziak Krzysztof , Mahmood Shameem , Wechalekar Ashutosh D.
Published: January 2024

Systemic light chain (AL) amyloidosis is a relapsing plasma cell disorder. Therapy is limited, particularly for triple‐class refractory disease. We report the use of belantamab mafodotin, a BCMA‐directed drug–antibody conjugate, for relapsed AL amyloidosis, including patients traditionally excluded from clinical trials. Thirty‐one patients were reviewed, with a median of three prior lines of therapy. The median follow‐up was 12 months (95% CI 4–19), and a median of five doses were delivered. The best haematological overall response rate was 71%, and the complete/very good partial response was 58%. Sixty‐eight percent had keratopathy and improved in all. Belantamab mafodotin has high efficacy and good tolerability in patients with relapsed AL amyloidosis.
Undoing Aid: UK Aid Cuts, Development Relationships and Resourcing Futures in Malawi
Authors: Morley Alyssa , Silver Rachel
Published: January 2024

The decision of the United Kingdom government to reduce its Official Development Assistance by £ 4.6 billion in 2020 was framed by its proponents as a nationalist response to a domestic financial crisis. This Conservative‐led austerity measure triggered the early closure of hundreds of aid projects globally. Concerned British politicians equated the cuts to moral failures as humanitarian and civil society actors claimed the lost funding would devastate the world's most vulnerable populations. In the vast space between British funders and the so‐called ‘beneficiaries’ of aid is a diverse cadre of mid‐level actors ‘doing’ and, in this case, ‘un‐doing’ development programming. This article examines their experiences in prematurely closing British‐funded projects in one postcolonial context, Malawi. Drawing upon semi‐structured interviews, the article explores the emotional, material and relational consequences of austerity. It builds on Didier Fassin's theorization of moral economies to argue that the timing and approach of this funding withdrawal violated the accepted moral economies of aid, breaching obligations between Malawian mid‐level aid workers and community members (including family) as well as among institutions. It concludes by considering how this particular rupture to the relational infrastructure of aid has prompted demands for recalibrated resourcing futures in Malawi.
The quest to end marginalization: Jordan's diversifying alignments in the post‐Arab Spring era
Authors: Altunisik Meliha , Koprulu Nur
Published: January 2024

Since 2017 Jordan has been diversifying its alignments while its relations with its traditional backers have become tenser. Drawing upon the existing literature that explains Jordan's alignment choices, this article aims to understand Jordan's diversification of its alignments and how they evolved in the post‐Arab Uprisings era. It is argued that although the regime security argument and the linkage between external and internal threats for explaining Jordan's alignment decisions have been very useful, to take these arguments further, there is a need to unpack regime security. The article, thus, introduces the importance of the content of the threat and from whom it is perceived to understand this complex interaction between external and domestic threat perceptions and how that interaction affects Jordan's alignment choices.
‘RISDM‘: species distribution modelling from multiple data sources in R
Authors: Foster Scott D. , Peel David , Hosack Geoffrey R. , Hoskins Andrew , Mitchell David J. , Proft Kirstin , Yang Wen‐Hsi , Uribe‐Rivera David E , Froese Jens G.
Published: January 2024

Species distribution models (SDMs) are usually based on a single data type, such as presence‐only (PO), presence‐absence (PA) or abundance (AA). Results from SDMs using single sources of data will suffer from inherent biases and limitations to that data type. For example, PO data contain sampling‐bias and PA/AA data are often less expansive and more sparse. Integrated SDMs (ISDMs) combine multiple data types and have recently emerged as a way to leverage strengths and minimise weaknesses of the different data types. They pose a common (distribution) model and separate observation models for each of the data types. The ‘RISDM' package for the R environment (www.r‐project.org) provides access to this modelling framework using functions for preparation, fitting, interpreting and diagnosing models. The functionality of the package is demonstrated here using synthetic data sets.
Stuck on you: Wind‐dispersed seeds attach to the external surfaces of a tree frog
Authors: Gould John , Valdez Jose W.
Published: January 2024

Many plants exploit the ability of animals to move in order to disperse their pollen and seeds. Despite the growing understanding of the role animals play in the reproductive lives of plants, there are few examples of amphibians contributing to these processes. We report on an Australian tree frog, Litoria fallax, interacting with and likely moving seeds of the broad‐leaved cumbungi, Typha orientalis, over short distances via external transport. Field observations revealed both juvenile and adult L. fallax individuals carrying typha seeds, which were adhered to the skin on the feet, legs, belly and dorsum. Approximately 30% of observed frogs were found to be carrying 1–14 seeds at a time. The small size and specialised fibre tufts of typha seeds, which enable them to be primarily dispersed by wind, also make them susceptible to being unintentionally picked up and transported by L. fallax as they move through aquatic environments. The moist surfaces of frogs, coupled with their presence in freshwater systems that can be dominated by typha, create favourable conditions for seed attachment. These findings highlight a previously unknown interaction between an amphibian and a plant that enables seed dispersal, supporting the need for further exploration into unexpected plant vectors.
Gender identity differences in the experiences of family stressors and violence among transgender and non‐binary individuals in China
Authors: Chan Randolph C. H. , Suen Yiu Tung , Leung Janice Sin Yu
Published: January 2024

Emerging research has demonstrated that transgender and non‐binary (TNB) individuals face an elevated risk of experiencing family rejection and violence. However, there remains a significant knowledge gap regarding how TNB individuals manage stressors and their gender identity within the family context, particularly in regions where TNB individuals are highly stigmatized and where legal protections against family violence are lacking. The present study represents one of the first pioneering efforts to provide large‐scale quantitative data examining the experiences of family stressors, the management of gender identity and expression, and family violence among TNB individuals in China. A national sample of 1063 TNB individuals in China was involved in the study. They completed questionnaires about their experiences of family stressors and violence. The results indicated that 76.0% of TNB individuals reported having encountered at least one form of violence perpetrated by their family members. Transfeminine individuals were more likely to report experiencing emotional and physical abuse, whereas transmasculine individuals were more likely to be subjected to gender identity and/or expression change efforts. Family stressors, including family non‐acceptance and the pressure to marry and reproduce, were positively associated with non‐disclosure of gender identity, the suppression of gender expression, and family violence. The findings underscore the substantial burden of family violence borne by TNB individuals in China, which warrants immediate legal, institutional, and social responses. Trans‐inclusive family violence prevention and intervention are urgently needed, with a focus on Chinese cultural factors and gender identity differences in violence screening and risk assessment.
Associations of polypharmacy with frailty severity and each frailty phenotype in community‐dwelling older adults: Itabashi Longitudinal Study on Aging
Authors: Daimaru Kaori , Osuka Yosuke , Kojima Narumi , Mizukami Katsuyoshi , Motokawa Keiko , Iwasaki Masanori , Inagaki Hiroki , Miyamae Fumiko , Okamura Tsuyoshi , Hirano Hirohiko , Awata Shuichi , Sasai Hiroyuki
Published: January 2024

Aim

Although polypharmacy and frailty are concerns in older adults, there is limited understanding of their association, particularly regarding frailty severity and its phenotypes within this population. This study aimed to examine the association between polypharmacy and frailty severity or frailty phenotypes in community‐dwelling older Japanese adults.

Methods

This cross‐sectional study included 1021 older adults from the Itabashi Longitudinal Study on Aging. Men accounted for 45.4%, and the mean age (standard deviation) was 77.9 (5.1) years. Participants were classified into frail (n = 67), pre‐frail (n = 543), and robust (n = 411) groups using the revised Japanese Cardiovascular Health Study criteria. Polypharmacy was defined as using five or more self‐reported prescription drugs. Ordinal and binomial logistic regression analyses examined the association between polypharmacy and frailty severity or frailty phenotypes (weight loss, weakness, exhaustion, slowness, and low activity). These models were adjusted for age, sex, body mass index, number of comorbidities, living status, employment status, years of education, as well as drinking and smoking habits.

Results

The prevalence of frailty in participants with and without polypharmacy was 10.1% and 5.0%, respectively. Participants with polypharmacy were more likely to have frailty (adjusted odds ratio [95% confidence interval], 1.89 [1.40–2.57]), weight loss (1.81 [1.00–3.27]), weakness (1.50 [1.08–2.09]), and slowness (2.25 [1.29–3.94]) compared with the no‐polypharmacy group.

Conclusions

Polypharmacy was associated with frailty severity and three frailty phenotypes. Longitudinal studies are required to investigate whether polypharmacy can predict the development and progression of frailty. Geriatr Gerontol Int 2024; 24: 196–201.
Unpacking intercity competitive relations in the global corporate spatial organization of manufacturing
Authors: Zhang Weiyang , Qian Yuxin
Published: January 2024

Despite being a traditional research topic in urban studies, competitive relations among cities have rarely been quantified in empirical research. Drawing on methods of social network analysis, this study aims to extract intercity competitive relations at the global scale based on the global corporate spatial organization of manufacturing. The geographies of competitive relations manifest different patterns from those of global city networks based on cooperative relations. This study finds an inverse U‐shaped relationship between cities’ connectivities and their gross intensity of competition. Although most global cities have unique positions in global manufacturing competition, intensive competition occurs among some global cities, whereas extensive competition exists between wide‐ranging cities with weak global connectivities. Furthermore, there is strong competition among cities of similar size and among those located in the same region. This research not only re‐examines global intercity relations from a competitive perspective but also informs the formulation of policy‐making on competition strategies of cities.
Fabrication of mechanically robust nanoporous ZrSiO4 ceramics at low temperature with a low doping level of Mn dopant
Authors: Fu Le , Zhou Huasi , Klintberg Lena , Engqvist Håkan , Xia Wei
Published: January 2024

Zircon (ZrSiO4) ceramics have been widely used in many fields due to their excellent physical and chemical properties. However, ZrSiO4 ceramics typically possess moderately low mechanical properties, which hinders their wider application. Meanwhile, elevated temperatures (∼1500°C) are required to obtain high‐purity synthetic ZrSiO4 ceramics, which is time‐ and energy‐consuming. In the present study, we prepared mechanically robust ZrSiO4 ceramics at low temperature (∼1170°C) with a low doping level of Mn dopant (<2 mol%). The ZrSiO4 ceramic processed by hot isostatic pressing with .5 mol% Mn dopant achieved the highest flexural strength (512 MPa), elastic modulus (341 GPa), and nanohardness (20.8 GPa). These values are significantly higher than conventional ZrSiO4 ceramics. The strengthening mechanisms of the prepared ZrSiO4 ceramics were attributed to the formation of homogeneously‐distributed nanopores due to incomplete densification and submicron ZrSiO4 grains (∼300 nm). The nanopores avoided stress concentration and deflected microcracks during loading, and the submicron ZrSiO4 grains endowed the ZrSiO4 ceramics with grain refinement strengthening. The results reported in this study would offer guidance to fabricate mechanically robust ZrSiO4 ceramics at low temperatures with a low doping level of dopant.
Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting
Authors: Daudén Esteban , Escario Elena , Martos‐Cabrera Luisa , Armesto Susana , Herrera‐Acosta Enrique , Vidal David , Vilarrasa Eva , Rivera Raquel , de la Cueva Pablo , Martorell Antonio , Ballesca Ferran , Belinchón Isabel , Carretero Gregorio , Rodríguez Lourdes , Romero‐Maté Alberto , Pujol‐Montcusí J. , Salgado Laura , Sahuquillo‐Torralba Antonio , Coto‐Segura Pablo , Baniandrés Ofelia , Feltes R. , Riera‐Monroig Josep , Garrido Jesus , Llamas‐Velasco Mar
Published: January 2024

Background

Biological therapy dose modification is a common practice in the long‐term treatment of plaque psoriasis.

Objective

The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC‐DR) strategy and assess its safety and cost implications.

Methods

A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow‐up.

Results

In 63/347 patients with an initial standard dose regimen, SEC‐DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC‐DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed.

Limitations

The proper of the study designed and the arbitrary definition of “DR success.”

Conclusion

Off‐label SEC‐DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long‐term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.
A meta‐analysis examining the impact of open surgical therapy versus minimally invasive surgery on wound infection in females with cervical cancer
Authors: Yun Zhouhui , Li Xiumin , Zhu Di , Li Lijie , Jiang Shenglin
Published: January 2024

A meta‐analysis study was executed to measure the effect of minimally invasive surgery (MIS) and open surgical management (OSM) on wound infection (WI) in female's cervical cancer (CC). A comprehensive literature study till February 2023 was applied and 1675 interrelated investigations were reviewed. The 41 chosen investigations enclosed 10 204 females with CC and were in the chosen investigations' starting point, 4294 of them were utilizing MIS, and 5910 were utilizing OSM. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilized to compute the value of the effect of MIS and OSM on WI in female's CC and by the dichotomous approaches and a fixed or random model. The MIS had significantly lower WI (OR, 0.23; 95% CI, 0.15–0.35, p < 0.001) with no heterogeneity (I2 = 0%) and postoperative aggregate complications (PACs) (OR, 0.49; 95% CI, 0.37–0.64, p < 0.001) in females with CC and compared OSM. However, MIS compared with OSM in females with CC and had no significant difference in pelvic infection and abscess (PIA) (OR, 0.59; 95% CI, 0.31–1.16, p = 0.13). The MIS had significantly lower WI, and PACs, though, had no significant difference in PIA in females with CC and compared with OSM. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta‐analysis.
Prognostic value of longitudinal HbA1c variability in predicting the development of diabetic sensorimotor polyneuropathy among patients with type 2 diabetes mellitus: A prospective cohort observational study
Authors: Lai Yun‐Ru , Chiu Wen‐Chan , Huang Chih‐Cheng , Cheng Ben‐Chung , Yu I‐Hsun , Kung Chia‐Te , Lin Ting Yin , Chiang Hui Ching , Kuo Chun‐En Aurea , Lu Cheng‐Hsien
Published: January 2024

Aims/Introduction

This prospective cohort study aims to identify the optimal measure of glycated hemoglobin (HbA1c) variability and to explore its relationship with the development of new diabetic sensorimotor polyneuropathy (DSPN) in individuals with type 2 diabetes mellitus, building upon previous cross‐sectional studies that highlighted a significant association between HbA1c visit‐to‐visit variability and DSPN.

Materials and Methods

In a prospective study, 321 participants diagnosed with type 2 diabetes mellitus underwent comprehensive clinical assessments, neurophysiologic studies, and laboratory evaluations at enrollment and follow‐up. Various indices, including HbA1c standard deviation (HbA1c SD), coefficient of variation (HbA1c CV), HbA1c change score (HbA1c HVS), and average real variability (HbA1c ARV), were employed to calculate the visit‐to‐visit variability HbA1c based on 3 month intervals. The investigation focused on examining the associations between these indices and the development of new DSPN.

Results

The average follow‐up duration was 16.9 ± 6.9 months. The Cox proportional hazards model identified age (P = 0.001), diabetes duration (P = 0.024), and HbA1C ARV (P = 0.031) as the sole factors associated with the development of new DSPN. Furthermore, the cumulative risk of developing DSPN over 1 year demonstrated a significant association with HbA1C ARV (P = 0.03, log‐rank test).

Conclusions

Apart from age and diabetes duration, HbA1c variability emerged as a robust predictor for the occurrence of new DSPN. Among the various measures of HbA1c variability evaluated, HbA1c ARV demonstrated the highest potential as a reliable indicator for anticipating the onset of new DSPN.
Vascularization of the gastrointestinal tract of the bottlenose dolphin (Tursiops truncatus, Montagu 1821)
Authors: Gerussi Tommaso , Graïc Jean‐Marie , Orekhova Ksenia , Cozzi Bruno , Grandis Annamaria
Published: January 2024

Odontocetes primarily rely on fish, cephalopods, and crustaceans as their main source of nutrition. In the digestive system, their polygastric complex exhibits similarities to that of their closest terrestrial relatives such as cows, sheep, and giraffes, while the entero‐colic tract shares similarities with terrestrial carnivores. The morphology, caliber, and structure of the odontocete intestine are relatively constant, and, since there is no caecum, a distinction between the small and large intestine and their respective subdivisions is difficult. To address this issue, we used the intestinal vascularization pattern, specifically the course and branching of the celiac artery (CA) and the cranial and caudal mesenteric arteries (CrMA and CdMA). A series of pictures and dissections of 10 bottlenose dolphins (Tursiops truncatus) were analyzed. Additionally, we performed a cast by injecting colored polyurethane foam in both arteries and veins to measure the caliber of the arteries and clarify their monopodial or dichotomous branching. Our results showed the presence of multiple duodenal arteries (DAs) detaching from the CA. The CrMA gave origin to multiple jejunal arteries, an ileocolic artery (ICA), and, in six cases, a CdMA. In four specimens, the CdMA directly originated from the abdominal aorta. The ICA gave rise to the mesenteric ileal branches (MIB) and mesenteric anti‐ileal branches and the right colic arteries (RCA) and the middle colic arteries. From the CdMA originated the left colic and cranial rectal arteries (LCA and CrRA). The measurements revealed a mixed monopodial and dichotomous branching scheme. The analysis of the arteries and their branching gave us an instrument, based on comparative anatomy, to distinguish between the different intestinal compartments. We used the midpoint of anastomoses between MIB and RCA to indicate the border between the small and the large intestine, and the midpoint of anastomoses between LCA and CrRA, to tell the colon from the rectum. This pattern suggested an elongation of the duodenum and a shortening of the colic tract that is still present in this species. These findings might be related to the crucial need to possess a long duodenal tract to digest prey ingested whole without chewing. A short aboral part is also functional to avoid gas‐producing colic fermentation. The rare origin of the CdMA on the CrMA might instead be a consequence of the cranial thrust of the abdominopelvic organs related to the loss of the pelvic girdle that occurred during the evolution of cetaceans.
In vitro evaluation of the application of an optimized xylanase cocktail for improved monogastric feed digestibility
Authors: Ramatsui Lebogang , Sithole Tariro , Gandla Madhavi L. , Jönsson Leif J. , Edkins Adrienne L. , Malgas Samkelo , Pletschke Brett I.
Published: January 2024

Xylanases from glycoside hydrolase (GH) families 10 and 11 are common feed additives for broiler chicken diets due to their catalytic activity on the nonstarch polysaccharide xylan. This study investigated the potential of an optimized binary GH10 and GH11 xylanase cocktail to mitigate the antinutritional effects of xylan on the digestibility of locally sourced chicken feed. Immunofluorescence visualization of the activity of the xylanase cocktail on xylan in the yellow corn of the feed showed a substantial collapse in the morphology of cell walls. Secondly, the reduction in the viscosity of the digesta of the feed by the cocktail showed an effective degradation of the soluble fraction of xylan. Analysis of the xylan degradation products from broiler feeds by the xylanase cocktail showed that xylotriose and xylopentaose were the major xylooligosaccharides (XOS) produced. In vitro evaluation of the prebiotic potential of these XOS showed that they improved the growth of the beneficial bacteria Streptococcus thermophilus and Lactobacillus bulgaricus. The antibacterial activity of broths from XOS‐supplemented probiotic cultures showed a suppressive effect on the growth of the extraintestinal infectious bacterium Klebsiella pneumoniae. Supplementing the xylanase cocktail in cereal animal feeds attenuated xylan's antinutritional effects by reducing digesta viscosity and releasing entrapped nutrients. Furthermore, the production of prebiotic XOS promoted the growth of beneficial bacteria while inhibiting the growth of pathogens. Based on these effects of the xylanase cocktail on the feed, improved growth performance and better feed conversion can potentially be achieved during poultry rearing.
Context‐dependent accuracy of the cobas plasma separation card for HCV RNA viral load measurement
Authors: Qureshi Huma , Duran Ana Carrasco , Mahmood Hassan , Sarwar Zahida , Mahmood Khalid , Midde Krishna , Canchola Jesse A. , Parkin Neil T. , La Brot Benjamin
Published: January 2024

Collection and preservation of plasma are challenging in remote or under‐resourced settings. The cobas® Plasma Separation Card (PSC) is an alternative specimen type for blood‐borne pathogen nucleic acid quantitation. We assessed PSC as a specimen type for HCV RNA quantitation in Pakistan. Plasma from venous blood and PSC from finger prick blood were prepared at two sites: Site 1 (in Lahore, n = 199) consisted of laboratory‐based outpatient clinics. Specimens were prepared in the same facility and stored frozen. Site 2 was a catchment area within a resource‐limited, semi‐urban locality of Islamabad with limited access to healthcare services (n = 151). Community public health outreach staff collected blood and prepared the PSC in the participants' homes. Specimens were transported to the central hepatitis laboratory in Lahore to be stored frozen until tested. HCV RNA testing was performed using the cobas HCV RNA test in a central laboratory. Concordance with respect to RNA detectability was high at Site 1 (97.4%), but lower at Site 2 (82.4%). At Site 1, HCV viral load in plasma and PSC were well correlated across the linear range with a 0.21 log10 IU/mL mean bias toward higher concentrations in PSC. At Site 2, HCV viral load in plasma and PSC were poorly correlated. There was a 0.11 log10 IU/mL mean bias toward higher concentrations in PSC. PSC performance can be excellent in underserved settings where refrigerated transport of traditional specimens is difficult. In very challenging field settings, extra support must be provided to ensure correct specimen collection and handling.
Total factor productivity and state ownership: Evidence from China's 2008 stimulus package
Authors: Han Shi‐zhuan , Duan Taotao , Gao Han , Zhou Tianhang , Li Jie
Published: January 2024

We examine the impact of China's economic stimulus plan in 2008 on the total factor productivity (TFP) of China's listed firms. We hypothesize that firms operating in regions characterized by greater resource misallocation would experience a more pronounced decline in TFP following the implementation of the stimulus plan. To gauge the extent of resource misallocation, we employ the proportion of state‐owned enterprises (SOEs) as a measure. Our findings reveal a substantial decrease in TFP for firms located in provinces with higher SOE shares compared to those in provinces with lower SOE shares, amounting to approximately 9.2%. These results highlight the unintended policy consequence of the stimulus plan for firm‐level productivity in China.
Embracing the future: Technological developments and sustainability in health professional education
Authors: Pusic Martin , Crampton Paul E. S. , Eva Kevin W.
Published: January 2024

Pusic, Crampton, and Eva announce the release of Medical Education's 15th annual State of the Science issue: Embracing the Future
Rethinking the value proposition of assessment at a time of rapid development in generative artificial intelligence
Authors: Fawns Tim , Schuwirth Lambert
Published: January 2024

The authors argue for evolving assessment practices by focusing on their value proposition to educators (producing the medical graduates needed for society) rather than protecting existing processes.
The alternative sigma factor RpoS regulates Pseudomonas aeruginosa quorum sensing response by repressing the pqsABCDE operon and activating vfr
Authors: Muriel‐Millán Luis Felipe , Montelongo‐Martínez Luis Fernando , González‐Valdez Abigail , Bedoya‐Pérez Leidy Patricia , Cocotl‐Yañez Miguel , Soberón‐Chávez Gloria
Published: January 2024

Pseudomonas aeruginosa is an important opportunistic pathogen. Several of its virulence‐related processes, including the synthesis of pyocyanin (PYO) and biofilm formation, are controlled by quorum sensing (QS). It has been shown that the alternative sigma factor RpoS regulates QS through the reduction of lasR and rhlR transcription (encoding QS regulators). However, paradoxically, the absence of RpoS increases PYO production and biofilm development (that are RhlR dependent) by unknown mechanisms. Here, we show that RpoS represses pqsE transcription, which impacts the stability and activity of RhlR. In the absence of RpoS, rhlR transcript levels are reduced but not the RhlR protein concentration, presumably by its stabilization by PqsE, whose expression is increased. We also report that PYO synthesis and the expression of pqsE and phzA1B1C1D1E1F1G1 operon exhibit the same pattern at different RpoS concentrations, suggesting that the RpoS‐dependent PYO production is due to its ability to modify PqsE concentration, which in turn modulates the activation of the phzA1 promoter by RhlR. Finally, we demonstrate that RpoS favors the expression of Vfr, which activates the transcription of lasR and rhlR. Our study contributes to the understanding of how RpoS modulates the QS response in P. aeruginosa, exerting both negative and positive regulation.
Circular RNA CircACAP2 regulates temporomandibular joint osteoarthritis via miR‐21‐5p/PLAG1 axis
Authors: Chen Hongyu , Qu Zhuli , Shi Tingting , Zhao Huaqiang , Huang Shengdong , Ma Chuan
Published: January 2024

Objectives

The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR‐21‐5p may participate in the TMJOA development and the interaction between circRNA‐ACAP2 (CircACAP2) and miR‐21‐5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA.

Materials and Methods

The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR‐21‐5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual‐luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model.

Results

The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR‐21‐5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models.

Conclusions

The present study unveiled that CircACAP2/miR‐21‐5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA.
Combining bioenergetics and movement models to improve understanding of the population consequences of disturbance
Authors: Chudzińska Magda , Klementisová Katarína , Booth Cormac , Harwood John
Published: January 2024

We developed dynamic bioenergetics models to investigate how behavioural responses to anthropogenic disturbance events might affect the population dynamics of three marine mammal species (harbour porpoise, grey seal and harbour seal) with contrasting life‐history traits (capital versus income breeders) and movement behaviour (resident versus nomadic). We used these models to analyse how individual vital rates were affected by differences in the probability of disturbance and the duration of any behavioural response, while taking account of uncertainty in the model parameters and heterogeneity in behaviour. The outputs of individual movement models and telemetry data were then used to determine how the probability of exposure might vary among species, individuals, and geographical locations. We then demonstrate how these estimated probabilities of exposure can be translated into probabilities of disturbance. For illustrative purposes, we modelled the potential effects of a temporary decrease in energy assimilation associated with a series of disturbance events that might realistically occur during the construction of an offshore windfarm. Offspring starvation mortality was the vital rate that was most affected by these disturbance events. Monitoring of rate should be considered as standard practice so that populations responses can be detected as early as possible. Predicted effects on individual vital rates depended on the species' movement behaviour and the likely density of animals where the modelled construction activity was assumed to take place. The magnitude of these effects also depended critically on the assumed duration of the reduction in energy assimilation. No direct estimates of this variable are currently available, but we suggest some ways in which it could be estimated. The described approach could be extended to other species and activities, given sufficient information to parameterise the component models. However, we emphasise the need to account for among‐individual heterogeneities and uncertainties in the values of the many model parameters.
The origin of excavator nesting behavior and its impact on the evolution of Neotropical parrots
Authors: Ramírez‐Herranz Myriam , Sayol Ferran , Rios Rodrigo S. , Antonelli Alexandre , Squeo Francisco A.
Published: January 2024

How the origin of novel behaviors can shape the evolutionary trajectory of organisms in response to environmental change remains poorly understood. Birds, especially those with big brains like parrots, are benchmarks for their behavioral innovation capacity in novel environments. Here, we assess whether and how the emergence of open areas in the Neotropics that started in the middle Miocene influenced the evolution of nesting behavior in parrots and how they triggered changes in other life‐history traits. To address these questions, we use a phylogenetic‐based analyses of trait evolution in the subfamily Arinae (Neotropical parrots), focusing on habitat, nesting behavior, morphology, and life‐history traits (clutch size, incubation period and fledging period). Evolutionary reconstructions show that transitions to excavating behavior mostly happened when species colonized open areas, providing evidence that this behavior originated in open environments. Evolutionary models suggest that the new open areas and the excavator nesting behavior exerted new selective pressures on morphology and life‐history traits, leading to evolutionary changes towards larger clutch sizes and shorter fledging periods in excavator parrots. Our study indicates that excavator nesting behavior in Neotropical parrots has likely played a key role in allowing them to exploit the ecological opportunities available in newly formed open biomes.
Transposable elements contribute to the establishment of the glycine shuttle in Brassicaceae species
Authors: Triesch S. , Denton A. K. , Bouvier J. W. , Buchmann J. P. , Reichel‐Deland V. , Guerreiro R. N. F. M. , Busch N. , Schlüter U. , Stich B. , Kelly S. , Weber A. P. M.
Published: January 2024

C3‐C4 intermediate photosynthesis has evolved at least five times convergently in the Brassicaceae, despite this family lacking bona fide C4 species. The establishment of this carbon concentrating mechanism is known to require a complex suite of ultrastructural modifications, as well as changes in spatial expression patterns, which are both thought to be underpinned by a reconfiguration of existing gene‐regulatory networks. However, to date, the mechanisms which underpin the reconfiguration of these gene networks are largely unknown.

In this study, we used a pan‐genomic association approach to identify genomic features that could confer differential gene expression towards the C3‐C4 intermediate state by analysing eight C3 species and seven C3‐C4 species from five independent origins in the Brassicaceae.

We found a strong correlation between transposable element (TE) insertions in cis‐regulatory regions and C3‐C4 intermediacy. Specifically, our study revealed 113 gene models in which the presence of a TE within a gene correlates with C3‐C4 intermediate photosynthesis. In this set, genes involved in the photorespiratory glycine shuttle are enriched, including the glycine decarboxylase P‐protein whose expression domain undergoes a spatial shift during the transition to C3‐C4 photosynthesis. When further interrogating this gene, we discovered independent TE insertions in its upstream region which we conclude to be responsible for causing the spatial shift in GLDP1 gene expression.

Our findings hint at a pivotal role of TEs in the evolution of C3‐C4 intermediacy, especially in mediating differential spatial gene expression.
Upstream and downstream implementation arrangements in two‐level games. A focus on administrative simplification in the Italian National Recovery and Resilience Plan
Authors: Di Mascio Fabrizio , Natalini Alessandro , Profeti Stefania
Published: January 2024

The onset of the European NGEU program represented for European member states a formidable opportunity for post‐pandemic recovery and yet a significant challenge at the same time: to receive and retain EU funds, each state had to promptly draw up a National Recovery and Resilience Plan—NRRP) and commit to a pressing timetable for its implementation. Regarding this challenge, the Italian government's response is a case in point: first, Italy is by far the largest beneficiary of NGEU funds; second, it has long had a reputation for being laggard in both the implementation of European directives and the spending of cohesion policy structural funds; and the formulation of the NRRP, the design of the governance in charge of its implementation, and implementation itself, occurred at a particular moment in the country's political life. Based on these premises, the article examines the upstream process by which the Italian government designed the implementation arrangements for the adoption of simplification policies under the NRRP and their downstream recalibration in the first two years, taking the implementation arrangements as the dependent variable. Analytically, the focus is on the interplay between the pressures of EU timetables and internal political dynamics, be they the legacy or strategic political considerations on the part of national policymakers, in determining the design and eventual re‐design of implementation arrangements as the plan unfolds.
Oral candida lesions and Candida tropicalis: Potential prognostic markers in end‐of‐life cancer patients
Authors: Shimosato Maiko , Kada Shinpei , Yase Eriko , Sakane Naoki
Published: January 2024

Aims

Oral candidosis is common in patients with end‐of‐life cancer; however, its prognosis is unclear. We aimed to assess oral candidosis and Candida species as prognostic indicators in palliative care for these patients.

Methods

We consecutively included palliative care patients, assessed for candidosis via microbiological techniques, and classified into three groups by the extent of oral lesions. The association between oral candidosis and overall survival was assessed using a Cox proportional hazards model adjusted by performance status (PS).

Results

We studied 142 patients (median age 77; 52.8% women) with a 76.1% oral candidosis prevalence. Candida albicans (80.6%) was the most common species. Oral lesions were classified as none, grade 1 (28.7%), or ≥ grade 2 (14.8%). During follow‐up, Cox models identified ≥grade 2 lesions (aHR = 2.04; 95% CI: 1.18–3.54; p = .011) and Candida tropicalis (aHR = 2.38; 95% CI: 1.03–5.55; p = .044) as predictors.

Conclusion

The extent of oral candidosis lesions or the presence of C. tropicalis may serve as prognostic indicator in patients with end‐of‐life cancer. Therefore, solely concentrating on the prevalence and frequency of fungal species may be insufficient for predicting life prognosis; it is advisable to assess these parameters through both visual examination and culture.
Exemplar or facilitator: An exploration of the lived experience of nurse mentors supporting the adaptation of internationally educated nurses
Authors: Smith Carly , Cantillon Peter
Published: January 2024

Introduction

Deficits in nursing workforces have led to major increases in overseas recruitment in many countries. Internationally educated nurses recruited within Ireland must complete an adaptation programme before they can practice nursing, a process contingent on the support from nurse mentors. However, it is becoming progressively difficult to identify nurses willing to act as mentors, threatening viability of overseas nurse recruitment. This research set out to address this problem by exploring the lived experiences of nurse mentors during the adaptation programme.

Methods

An interpretative phenomenological analysis research design was utilised to explore the experiences of nurse mentors. Semi‐structured interviews were conducted with a maximum variance sample of 11 nurse mentors. The data were subjected to an Interpretive Phenomenological Analysis (IPA) sequential analytical approach yielding integrative themes.

Results

The lived experiences of participants coalesced into three conceptual themes, mentor identity, sustainability, and learner socialisation. Participants who self‐identified as ‘mentor exemplars’ expressed more negative perceptions of the role when compared with nurses who positioned themselves as ‘mentor facilitators’. Nurse mentors were challenged by the complexities of intercultural dissonance and insufficient time and training for their mentoring role because of the pressures of clinical service.

Conclusion

Although mentorship is essential for the integration of internationally educated nurses, the sustainability of the mentorship role is contingent on how it is supported through training and protected within busy clinical environments. Critically, nurse mentors need to learn how to conceptualise their role as one of facilitating the development of others rather than presenting themselves as exemplary role models.
Differentiating patient characteristics between platelet refractory patients with and without antibodies to human leukocyte antigens
Authors: Liu Kelsey , Stephens Laura , Nedelcu Elena , Bakhtary Sara
Published: January 2024

Background

Predicting whether a patient's platelet refractoriness (PR) is due to immune or nonimmune causes can be challenging. This study compared the demographics and clinical history of PR patients with human leukocyte antigen (HLA) antibodies (HLA‐PR) versus PR patients without HLA antibodies.

Materials and Methods

A retrospective review of all patients with PR consults at a single institution over a 3‐year period was performed. Patient charts were reviewed for all patients with confirmed PR, and demographic information (e.g., sex, race and ethnicity, preferred language) and clinical history (e.g., pregnancy, transfusion, primary diagnosis) were collected. Patient characteristics were compared among the HLA and non‐HLA cohorts.

Results

A total of 295 patients with confirmed PR were identified, of whom approximately 70% did not have HLA antibodies and 30% did. Approximately 84% of the HLA‐PR cohort was female. A history of transfusions was not associated with HLA‐PR (p = .1). A history of pregnancy was strongly associated with the occurrence of HLA‐PR (p < .001). Splenomegaly was associated with PR in the absence of HLA alloimmunization whereas infection, fever, bleeding, and disseminated intravascular coagulation were not.

Conclusion

In this single‐institution retrospective review, a history of pregnancy was strongly associated with HLA‐PR, whereas a history of transfusion was not.
Quantifying Offense and Defense Workloads in Professional Rugby Union
Authors: Stevens Luke J. , Hopkins Will G. , Chittenden Jessica A. , Koper Bianca Z. , Smith Tiaki Brett
Published: January 2024

Purpose: Rugby union is a contact team sport demanding high levels of physical capacity, and understanding the match workloads can be useful to inform training. In this study, the factors influencing locomotion and contact workloads for offensive and defensive ball-in-play periods are quantified. Methods: Locomotion and contact metrics were collected from global positioning system units and videos for 31 professional players of a Super Rugby team across 14 games in the 2021 season. Data were analyzed with a generalized mixed-model procedure that included effects for type of play, playing position, match outcome, and ball-in-play time. Magnitudes were assessed with standardization, and evidence for substantial magnitudes was derived from sampling uncertainty. Results: When offense was compared to defense, most metrics showed decisively substantial increases (small to moderate) for forwards and backs. There was decisive evidence that locomotion metrics were substantially lower (large differences) and contact metrics were higher (very large differences) when comparing forwards to backs on offense and defense. When winning was compared to losing, there was good evidence that forwards experienced small increases in overall workload on defense, and backs experienced a small increase in high-speed running and a moderate decrease in contacts on offense. Match-to-match changes associated with ball-in-play time, attributed to fatigue, were decisive (moderate to very large) across most metrics for forwards and backs in offense and defense. Conclusions: The increased locomotion and contact workloads in offensive periods and the differing physical requirements between positions and match outcomes for both types of play are novel findings that should aid practitioners in designing effective training.
Septins provide microenvironment sensing and cortical actomyosin partitioning in motile amoeboid T lymphocytes
Authors: Zhovmer Alexander S. , Manning Alexis , Smith Chynna , Nguyen Ashley , Prince Olivia , Sáez Pablo J. , Ma Xuefei , Tsygankov Denis , Cartagena-Rivera Alexander X. , Singh Niloy A. , Singh Rakesh K. , Tabdanov Erdem D.
Published: January 2024

The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For amoeboid motility, lymphocytes do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape and steric interactions with the microenvironment. However, the exact mechanism of amoeboid motility remains elusive. Here, we report that septins participate in amoeboid motility of T cells, enabling the formation of F-actin and α-actinin–rich cortical rings at the sites of cell cortex–indenting collisions with the extracellular matrix. Cortical rings compartmentalize cells into chains of spherical segments that are spatially conformed to the available lumens, forming transient “hourglass”-shaped steric locks onto the surrounding collagen fibers. The steric lock facilitates pressure-driven peristaltic propulsion of cytosolic content by individually contracting cell segments. Our results suggest that septins provide microenvironment-guided partitioning of actomyosin contractility and steric pivots required for amoeboid motility of T cells in tissue-like microenvironments.
Single-cell joint profiling of multiple epigenetic proteins and gene transcription
Authors: Xiong Haiqing , Wang Qianhao , Li Chen C. , He Aibin
Published: January 2024

Sculpting the epigenome with a combination of histone modifications and transcription factor occupancy determines gene transcription and cell fate specification. Here, we first develop uCoTarget, utilizing a split-pool barcoding strategy for realizing ultrahigh-throughput single-cell joint profiling of multiple epigenetic proteins. Through extensive optimization for sensitivity and multimodality resolution, we demonstrate that uCoTarget enables simultaneous detection of five histone modifications (H3K27ac, H3K4me3, H3K4me1, H3K36me3, and H3K27me3) in 19,860 single cells. We applied uCoTarget to the in vitro generation of hematopoietic stem/progenitor cells (HSPCs) from human embryonic stem cells, presenting multimodal epigenomic profiles in 26,418 single cells. uCoTarget reveals establishment of pairing of HSPC enhancers (H3K27ac) and promoters (H3K4me3) and RUNX1 engagement priming for H3K27ac activation along the HSPC path. We then develop uCoTargetX, an expansion of uCoTarget to simultaneously measure transcriptome and multiple epigenome targets. Together, our methods enable generalizable, versatile multimodal profiles for reconstructing comprehensive epigenome and transcriptome landscapes and analyzing the regulatory interplay at single-cell level.