bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo‐controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor
Authors: Perin Emerson , Loveland Lacey , Caporusso Joseph , Dove Cyaandi , Motley Travis , Sigal Felix , Vartivarian Mher , Oliva Francisco , Armstrong David G ,   the VMNHU‐003 study group
Published: May 2023

To evaluate the status of a 7‐month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent‐to‐Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a t‐test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N = 44), there was a positive trend toward closure in the VM202 group from 3 to 6 months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound‐closing effects at month 6 (P = .0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (P = .0391, .0391, and .0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (P = .03 for all points). A potentially clinically meaningful 0.15 increase in Ankle‐Brachial Index was observed in the VM202 group at day 210 in the ITT population (P = .0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites.
Should Political Philosophers Attend to Victim Testimony?
Authors: Engelstad Ane
Published: May 2023

There is a growing recognition that victims of injustice may have privileged access to knowledge about the injustices they experience, and that injustices are perpetuated through silencing victims by taking them to be less credible, and through denying them the platform and capacity to speak. However, these are not ideas that political philosophers tend to engage with in a sustained manner, to the extent that they alter methodological approaches to be systematically attentive to victim testimony. In this article, I provide two arguments in favour of political philosophers attending to victim testimony, one moral, one epistemic, and demonstrate that the moral case has little purchase, but that the epistemic case is more successful. Then, I present the strongest case against including victim testimony in political philosophy, and I argue that it does not hold up to scrutiny. In so doing, I demonstrate how methodological practices in political philosophy could be improved through drawing on feminist social epistemology; attending to victim testimony can enrich political philosophy in epistemically acceptable ways, and it also corrects for a range of potential biases.
Electrophysiological study prior to planned pulmonary valve replacement in patients with repaired tetralogy of Fallot
Authors: Bouyer Benjamin , Jalal Zakaria , Daniel Ramirez F. , Derval Nicolas , Iriart Xavier , Duchateau Josselin , Roubertie François , Tafer Nadir , Tixier Romain , Pambrun Thomas , Cheniti Ghassen , Ascione Ciro , Yokoyama Masaaki , Kowalewski Christopher , Buliard Samuel , Chauvel Rémi , Arnaud Marine , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre , Cochet Hubert , Thambo Jean‐Benoit , Sacher Frederic
Published: May 2023

Aim

Ventricular arrhythmias (VAs) are the most common cause of death in patients with repaired Tetralogy of Fallot (rTOF). However, risk stratifying remains challenging. We examined outcomes following programmed ventricular stimulation (PVS) with or without subsequent ablation in patients with rTOF planned for pulmonary valve replacement (PVR).

Methods

We included all consecutive patients with rTOF referred to our institution from 2010 to 2018 aged ≥18 years for PVR. Right ventricular (RV) voltage maps were acquired and PVS was performed from two different sites at baseline, and if non‐inducible under isoproterenol. Catheter and/or surgical ablation was performed when patients were inducible or when slow conduction was present in anatomical isthmuses (AIs). Postablation PVS was undertaken to guide implantable cardioverter‐defibrillator (ICD) implantation.

Results

Seventy‐seven patients (36.2 ± 14.3 years old, 71% male) were included. Eighteen were inducible. In 28 patients (17 inducible, 11 non‐inducible but with slow conduction) ablation was performed. Five had catheter ablation, surgical cryoablation in 9, both techniques in 14. ICDs were implanted in five patients. During a follow‐up of 74 ± 40 months, no sudden cardiac death occurred. Three patients experienced sustained VAs, all were inducible during the initial EP study. Two of them had an ICD (low ejection fraction for one and important risk factor for arrhythmia for the second). No VAs were reported in the non‐inducible group (p < .001).

Conclusion

Preoperative EPS can help identifying patients with rTOF at risk for VAs, providing an opportunity for targeted ablation and may improve decision‐making regarding ICD implantation.
Upstream conduct and price authority with competing organizations
Authors: Andreu Enrique , Neven Damien , Piccolo Salvatore , Venturini Roberto
Published: May 2023

We characterize the degree of price authority that competing upstream principals award their downstream agents in a setting where these agents own private information about demand and incur nonverifiable distribution costs. Principals cannot internalize these costs through monetary incentives and design “permission sets” from which agents choose prices. The objective is to understand the forces shaping delegation and the constraints imposed on equilibrium prices. When principals behave noncooperatively, agents are biased toward excessively high prices because they pass on distribution costs to consumers. Hence, the permission set only features a price cap that is more likely to bind as products become closer substitutes, in sectors where distribution is sufficiently costly, and when demand is not too volatile. By contrast, when principals behave cooperatively, the optimal delegation scheme is richer and more complex. Because principals want to charge the monopoly price, the optimal permission set features a price floor when the distribution cost is sufficiently low, it features instead full discretion for moderate values of this cost, and only when it is high enough, a price cap is optimal. Surprisingly, while competition (as captured by stronger product substitutability) hinders delegation in the noncooperative regime, the opposite occurs when principals maximize industry profit.
Philosophical health: Unveiling the patient's personal philosophy with a person‐centred method of dialogue
Authors: de Miranda Luis , Loughlin Michael
Published: May 2023

Grounded in ideas about sense‐making and whole‐person care with a long intellectual heritage, the movement for Philosophical Health—with its specific conceptions of philosophical care and counselling—is a relatively recent addition to the ongoing debate about understanding better the perspectives of patients to improve health practice. This article locates the development of this movement within the context of broader discussions of person‐centred care (PCC), arguing that the approach advocated by defenders of philosophical health can provide a straightforward method for implementing PCC in actual cases. This claim is explained and defended with reference to the SMILE_PH method created by Luis de Miranda (Sense‐Making Interviews Looking at Elements of Philosophical Health), an approach recently trialled convincingly with people living with traumatic spinal cord injury.
Outcomes among hospitalized patients with dementia and behavioral disturbances when physical restraints are introduced
Authors: Singh Amteshwar , Gupta Ishaan , Wright Scott Mitchell , Harris Che Matthew
Published: May 2023

Background

Physical restraint use among patients hospitalized with dementia and behavioral disturbances has not been studied nationally in the United States.

Methods

National Inpatient Sample database years 2016 through 2020 were used to compare physically restrained and unrestrained patients with dementia and behavioral disturbances. Multivariable regression analyses were used to assess patient outcomes.

Results

There were 991,605 patients coded for dementia with behavioral disturbances. Among these, physical restraints were used with 64,390 (6.5%) and not with 927,215 (93.5%). Patients in the restrained group were younger (mean age standard error: 78.7 0.25 vs. ; p < 0.01) and more often male (59.0% vs. 45.8%; p < 0.01) compared to the unrestrained group. A higher proportion of Black patients were in the restrained group (15.2% vs. 11.8%; p < 0.01). Larger hospitals also made up a more significant proportion of restrained versus unrestrained patients (53.3% vs. 45.1%; p < 0.01). Those with physical restraints had longer lengths of stays (adjusted mean difference [aMD] = 2.6 days CI [2.2–3.0]; p < 0.01) and higher total hospital charges (aMD = $13,150 CI [10,827‐15,472]; p < 0.01). There were similar adjusted odds for in‐hospital mortality (adjusted odds ratio [aOR] = 1.0 [CI 0.95–1.1]; p = 0.28) and lower odds of being discharged to home after hospitalization (aOR = 0.74 [0.70–0.79]; <0.01) for patients with physical restraints compared to those without.

Conclusion

Among patients hospitalized with dementia and behavioral disturbances, those with physical restraints had greater hospital resource utilization outcomes. Attempts to limit physical restraint use whenever possible may improve outcomes in this vulnerable population.
Grand challenges and platform ecosystems: Scaling solutions for wicked ecological and societal problems
Authors: Ritala Paavo
Published: May 2023

The persistence of grand societal and environmental challenges demands attention from innovation management scholars and practitioners to find effective resolutions. Grand challenges are complex, uncertain, and evaluative and cannot be resolved by individual actors or organizations. Therefore, conventional forms of organizing do not suffice in the face of wicked problems like climate change or global inequality, which require continuous and varied attention and inputs. In this catalyst article, I argue that platform ecosystems—communities and groups of actors in different markets orchestrated through a digital platform and driven by combinations of economic and prosocial incentives—are an organizing form that can help effectively scale solutions for grand societal and environmental problems. This potential is based on three organizational elements of platform ecosystems: (1) coordination structures for orchestrating complementary inputs, (2) instigation and maintenance of collective action, and (3) generativity potential. I illustrate these arguments with practical examples of two platforms with the potential to resolve specific grand challenges: Patient Innovation, which orchestrates a community of innovators seeking to help treatment of chronic and rare diseases, and Excess Materials Exchange, which provides matching solutions to address the challenges associated with industrial material waste. The article concludes with an agenda for future research and practice on platform ecosystems and grand challenges.
Chylothorax secondary to subcutaneous cervical lipoma in a dog
Authors: Sumner S. M. , Makrygiannis E. J. , Bartges J. , Schmiedt C. W.
Published: May 2023

An 8‐year‐old male neutered American English Coonhound was presented for a 2‐day history of increased respiratory effort and rate with an occasional cough. Thoracic radiographs noted pleural effusion, which was chylous based on cytological and chemical evaluation. The dog also had a 2‐year history of a slow growing fatty mass in the right cervical region. A CT scan confirmed the large cervical fat attenuating mass extending from the base of the skull to the cranial thorax and right axillary region with compression of vascular structures. Severe bilateral effusion and secondary pulmonary atelectasis was noted within the thoracic cavity. It was elected to surgically remove the cervical mass and place a PleuralPort within the thoracic cavity. The mass was diagnosed as a lipoma and its removal led to rapid and complete resolution of chylothorax. Based on the literature search, this is the first case report of chylothorax secondary to a cervical mass or subcutaneous lipoma.
Efficacy of high‐level disinfection of endoscopes contaminated with Streptococcus equi subspecies equi with 2 different disinfectants
Authors: Nadruz Veridiana , Beard Laurie A. , Delph‐Miller Katherine M. , Larson Robert L. , Bai Jianfa , Chengappa Muckatira M.
Published: May 2023

Background

Prevention of spread of Streptococcus equi subspecies equi (S. equi) after an outbreak is best accomplished by endoscopic lavage of the guttural pouch, with samples tested by culture and real time, quantitative polymerase chain reaction (qPCR). Disinfection of endoscopes must eliminate bacteria and DNA to avoid false diagnosis of carrier horses of S. equi.

Hypothesis/Objectives

Compare failure rates of disinfection of endoscopes contaminated with S. equi using 2 disinfectants (accelerated hydrogen peroxide [AHP] or ortho‐phthalaldehyde [OPA]). The null hypothesis was that there would be no difference between the AHP and OPA products (based on culture and qPCR results) after disinfection.

Methods

Endoscopes contaminated with S. equi were disinfected using AHP, OPA or water (control). Samples were collected before and after disinfection and submitted for detection of S. equi by culture and qPCR. Using a multivariable logistic regression model‐adjusted probability, with endoscope and day as controlled variables, the probability of an endoscope being qPCR‐positive was determined.

Results

After disinfection, all endoscopes were culture‐negative (0%). However, the raw unadjusted qPCR data were positive for 33% AHP, 73% OPA, and 71% control samples. The model‐adjusted probability of being qPCR‐positive after AHP disinfection was lower (0.31; 95% confidence interval [CI], −0.03‐0.64) compared to OPA (0.81; 95% CI, 0.55‐1.06), and control (0.72; 95% CI, 0.41‐1.04).

Conclusion and Clinical Importance

Disinfection using the AHP product resulted in significantly lower probability of endoscopes being qPCR‐positive compared to the OPA product and control.
Embryonic inhibition of colony‐stimulating factor 1 receptor impacts craniofacial morphogenesis
Authors: Nagra Ashina , Katsube Motoki , Gao Wade , Rosin Jessica M. , Vora Siddharth R.
Published: May 2023

Objectives

Colony‐stimulating factor‐1 receptor (CSF1R) is vital for the recruitment of monocytes, and their proliferation and differentiation into functional osteoclasts. Mouse studies, where CSF1R and its cognate ligand are absent, have significant craniofacial phenotypes, but these have not been studied in detail.

Materials and Methods

Pregnant CD1 mice were fed diets laced with CSF1R inhibitor—PLX5622 starting at embryonic day 3.5 (E3.5) up to birth. Pups were collected at E18.5 to study CSF1R expression using immunofluorescence. Additional pups were studied at postnatal day 21 (P21) and P28 using microcomputed tomography (μCT) and Geometric Morphometrics, to evaluate craniofacial form.

Results

CSF1R‐positive cells were present throughout the developing craniofacial region, including the jaw bones, surrounding teeth, tongue, nasal cavities, brain, cranial vault and base regions. Animals exposed to the CSF1R inhibitor in utero had severe depletion of CSF1R‐positive cells at E18.5 and had significant differences in craniofacial form (size and shape) at postnatal timepoints. Centroid sizes for the mandibular and cranio‐maxillary regions were significantly smaller in CSF1R‐inhibited animals. Proportionally, these animals had a domed skull, with taller and wider cranial vaults and shortening of their midfacial regions. Mandibles were smaller vertically and anterio‐posteriorly, with proportionally wider inter‐condylar distances.

Conclusions

Embryonic inhibition of CSF1R impacts postnatal craniofacial morphogenesis, with significant influences on the mandibular and cranioskeletal size and shape. These data indicate that CSF1R plays a role in early cranio‐skeletal patterning, likely through osteoclast depletion.
Percutaneous Full Endoscopic Lumbar Discectomy for Symptomatic Adjacent Segment Disease after Lumbar Fusion in Elderly Patients
Authors: Feng Pin , Kong Qingquan , Zhang Bin , Liu Junlin , Ma Junsong , Hu Yuan
Published: May 2023

Purpose

Treatment of adjacent segment disease (ASD) is still controversial. The aim of this study was to evaluate the short‐term efficacy and safety and to analyze the technical advantages, surgical approach, and indications of percutaneous full endoscopic lumbar discectomy (PELD) in the treatment of ASD after lumbar fusion in elderly patients.

Methods

A retrospective of 32 patients with symptomatic ASD were accepted for PELD from October 2017 to January 2020. All patients used the transforaminal approach and recorded the operation time and intraoperative conditions. Preoperative, 3, 12, 24 months of postoperative and at the last follow‐up, the pain of back and leg of visual analog scale (VAS), Oswestry dysfunction index (ODI), and Japanese Orthopaedic Association Assessment Treatment Score (JOA) were performed, and the paired student's t test was used to the compare the continuous variables preoperatively and postoperatively. The clinical efficacy was evaluated according to MacNab standards. The lumbar MRI was performed to evaluate the decompression of the nerve roots, and the lumbar lateral and dynamic X‐rays were performed to evaluate the stability of the surgical segment.

Results

A total of 32 patients were included in the study, including 17 males and 15 females. The follow‐up time ranged from 24 to 50 months, with an average of (33.2 ± 8.1) months and an average operation time of (62.7 ± 28.1) minutes. Compared to preoperatively, the VAS score of the back and leg pain (p < 0.05), ODI (p < 0.05), and JOA (p < 0.05) postoperatively were significantly improved. At the last follow‐up, according to the modified MacNab standard assessment, 24 cases were excellent, five cases were good, and three cases were fair, the excellent and good rate was 90.65%. As for complications, one case had a small rupture of the dural sac during the operation, which was found but not repaired during the operation, and one case recurred after the operation. At the last follow‐up, there were three cases of intervertebral instability.

Conclusion

PELD showed satisfactory short‐term efficacy and safety in the management of ASD after lumbar fusion in elderly patients. Therefore, PELD might be an alternative choice for elderly patients with symptomatic ASD after lumbar fusion, but surgical indications must be strictly controlled.
Optimization of light/dark cycle in an extended photoperiod‐based speed breeding protocol for grain legumes
Authors: Mitache Mohammed , Baidani Aziz , Houasli Chafika , Khouakhi Khadija , Bencharki Bouchaib , Idrissi Omar
Published: May 2023

The use of high‐performing varieties could contribute to increase food legume production and meet the population demand. However, the long process of conventional breeding is a serious limitation that needs further acceleration of genetic improvement. Speed breeding based on extended photoperiod is one of the techniques that allows rapid generation turnover by accelerating the plant life cycle. The present study focused on optimizing the duration of extended photoperiod for lentil, chickpea and faba bean in a growth chamber with light‐emitting diode (LED) light sources. Significant differences in growth rate, biomass production, phenology, physiology, plant injury and yield components were observed depending on light phase durations (22, 18 and 14 h). Twenty‐two hours of light resulted in earlier flowering and maturity, but higher stress symptoms than the other two light treatments. However, vegetative development was almost normal with limited stress under 14 h of light, but late flowering and maturity. Interestingly, good plant establishment with limited stress and shorter vegetative cycle was observed under 18 h of light. Therefore, a photoperiod of 18 h of light/6 h of darkness could be advised for a rapid breeding protocol.
Widespread keratinocytic epidermal nevus with an associated chylous pericardial effusion
Authors: Rowe Georgina , Snyder Kristen M. , Treat James R.
Published: May 2023

A 17‐year‐old male presented for review of a widespread keratinocytic epidermal nevus (KEN) in the setting of a chronic pericardial effusion. Biopsy of the epidermal nevus revealed a KRAS mutation. Pericardiocentesis revealed a chylous effusion and magnetic resonance lymphangiogram demonstrated an underlying lymphatic malformation. There are rare case reports of KEN with an associated KRAS mutation. This case highlights the importance of being alert to epidermal nevus syndrome, particularly in patients with a widespread nevus and seemingly unrelated pathology.
Rationally Facing Death: Fear and Other Alternatives
Authors: Cholbi Michael
Published: May 2023

Explaining what emotions or attitudes it is rational for humans to have toward our own deaths and toward their mortality has been a central task within most philosophical traditions. This article critically examines the rationality of five emotions or attitudes that might be taken toward death: fear, insofar as death can harm us by reducing our overall level of well‐being; the related attitude of existential terror, a feeling of dismay or uncanniness directed at the prospect of our eventual non‐existence; regret, directed at our being constituted as mortals; anger or resentment; and gratitude. Our conclusion is that there is in all likelihood no specific emotion or attitude that we are rationally required to take toward death or mortality. Neither anger nor gratitude are rational attitudes toward death, and while fear, existential terror, and regret are stronger candidates for being rational attitudes toward death, it proves difficult to show that death rationally requires any particular emotions or attitudes on our part.
Using the social ecological model to identify challenges facing Latino immigrants
Authors: Moyce Sally , Comey Danika , Anderson Jacey , Creitz Adam , Hines Deborah , Metcalf Madeline
Published: May 2023

Background

New Latino immigrant populations face challenges and barriers when arriving in new immigrant destinations.

Objective

To better understand the challenges faced by Latino immigrants in a new immigrant destination by using the Social Ecological Model.

Design

This study solicited the perceptions of key informants and Latino immigrant participants through qualitative data collection methods to understand how to address and decrease barriers to healthcare services and community resources.

Sample

Researchers conducted semi‐structured interviews with two groups of respondents: 13 key informants and 30 Latino immigrants.

Measurements

Data were analyzed using thematic analysis and categorized based on the Social Ecological Model.

Results

Themes identified at the individual and interpersonal levels of the Social Ecological Model include fear of deportation and stress. Themes at the community level include cultural differences, discrimination, and a lack of exposure of the majority community to Latino immigrants. At the system level, researchers identified language barriers, the cost of healthcare, and housing. At the policy level, researchers identified legal status and occupational exploitation as challenges for this community.

Conclusion

Understanding the challenges faced by Latino immigrants requires multi‐level interventions to address barriers that prevent new immigrants from accessing community resources.
Hyperbolicity study of the modulation equations for the Benjamin–Bona–Mahony equation
Authors: Gavrilyuk Sergey , Lin Yu‐Hsi , Shyue Keh‐Ming
Published: May 2023

A complete study of the modulation equations for the Benjamin–Bona–Mahony equation is performed. In particular, the boundary between the hyperbolic and elliptic regions of the modulation equations is found. When the wave amplitude is small, this boundary is approximately defined by , where k is the wave number. This particular value corresponds to the inflection point of the linear dispersion relation for the BBM equation. Numerical results are presented showing the appearance of the Benjamin–Feir instability when the periodic solutions are inside the ellipticity region.
Congenital glaucoma in a tiger (Panthera tigris)
Authors: Dianis Allison E. , Pinard Chantale L. , Pagliarani Sara , Susta Leonardo , Dutton Christopher J.
Published: May 2023

Objective

To describe a case of congenital glaucoma in atiger (Panthera tigris).

Animal Studied

An 8‐month‐old intact female tiger wasreferred for suspected glaucoma of the right eye. The right eye was buphthalmicwith moderate episcleral injection, circumferential superficial cornealneovascularization, moderate corneal edema, and a fixed dilated pupil. Tapetalreflection was absent due to a mature cataract. Rebound tonometry under generalanesthesia revealed 70 mmHg and 21 mmHg in the right and left eye, respectively.

Procedure

A trans‐conjunctival enucleation was performedand the globe was submitted for histopathology.

Results

Histopathology revealed a thin sclera, amorphousmaterial contouring an imperforate and hypoplastic iridocorneal angle, ahypoplastic lens with severe anterior‐posterior compression, subcapsularepithelial hyperplasia, and Morganian globules, and segmental moderate retinalatrophy. Periodic acid‐Schiff stain highlighted segmental dilations of theDescemet's membrane. Masson trichrome stain highlighted a pre‐irido collagenmembrane.

Conclusion

The tiger's age and histopathologic findingsare consistent with congenital goniodysgenesis. This is the first known reportof congenital glaucoma in a tiger.
Myths and methodologies: Cardiopulmonary exercise testing for surgical risk stratification in patients with an abdominal aortic aneurysm; balancing risk over benefit
Authors: Bailey Damian M. , Davies Richard G. , Rose George A. , Lewis Michael H. , Aldayem Ahmed Abd , Twine Chistopher P. , Awad Wael , Jubouri Matti , Mohammed Idhrees , Mestres Carlos A. , Chen Edward P. , Coselli Joseph S. , Williams Ian M. , Bashir Mohamad ,   The International Academic Surgical Consortium (THALAMUS)
Published: May 2023

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure‐induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom‐limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring ‘myth’ that AAA patients should be fearful of and avoid rigorous exercise. On the contrary, by appraising fundamental vascular mechanobiological forces associated with exercise, in conjunction with ‘methodological’ recommendations for risk mitigation specific to this patient population, we highlight that the benefits conferred by cardiopulmonary exercise testing and exercise training across the continuum of intensity far outweigh the short‐term risks posed by potential AAA rupture.
Mite diversity and intra-plant distribution in mango crop
Authors: Melo André S. , Melo José W.S. , Paz-neto Antônio A. , Gondim-junior Manoel G.C.
Published: May 2023

Effective management of arthropod communities in agricultural environments requires knowledge of the diversity and distribution of species that inhabit host crops. Therefore, we conducted this study to evaluate the richness, abundance, and intra-plant distribution of the most abundant mite species in mango plants. Leaves or reproductive structures were collected monthly considering the different canopy quadrants (North, South, East, and West), the position of the branch (basal, median, and apical), and, in the case of leaves, their position on the branch (basal, median, and apical). A total of 28 species belonging to 12 mite families were identified. Cisaberoptus kenyae, Vilaia pamithus, and Oligonychus mangiferus were the most abundant phytophagous species, accounting for 87%, 6%, and 3% of the total number of mites collected, respectively. Vilaia pamithus was the most abundant species in the southern quadrant. Amblyseius largoensis (Phytoseiidae) and Cunaxa sp1. (Cunaxidae) were the most abundant among the predators (15.1% and 13.1%, respectively). The highest level of diversity was observed in the basal and median leaves of the basal and median branches of mangoes. The intra-plant distribution of these species was influenced by plant architecture and geographical position. Most species were found on mango leaves, whereas other species colonized inflorescences and/or fruits, but at low densities. In this study, we found considerable diversity of phytophagous and predator mites in mango plants. These predator mites may be crucial for controlling mango pests.
Distributional learning of musical pitch despite tone deafness in individuals with congenital amusia
Authors: Zhu Jiaqiang , Chen Xiaoxiang , Chen Fei , Zhang Caicai , Shao Jing , Wiener Seth
Published: May 2023

Congenital amusia is an innate and lifelong deficit of music processing. This study investigated whether adult listeners with amusia were still able to learn pitch-related musical chords based on stimulus frequency of statistical distribution, i.e., via distributional learning. Following a pretest-training-posttest design, 18 amusics and 19 typical, musically intact listeners were assigned to bimodal and unimodal conditions that differed in distribution of the stimuli. Participants' task was to discriminate chord minimal pairs, which were transposed to a novel microtonal scale. Accuracy rates for each test session were collected and compared between the two groups using generalized mixed-effects models. Results showed that amusics were less accurate than typical listeners at all comparisons, thus corroborating previous findings. Importantly, amusics—like typical listeners—demonstrated perceptual gains from pretest to posttest in the bimodal condition (but not the unimodal condition). The findings reveal that amusics' distributional learning of music remains largely preserved despite their deficient music processing. Implications of the results for statistical learning and intervention programs to mitigate amusia are discussed.
Magnetorheology in unsteady fields: From uniaxial DC to rotating AC fields
Authors: Terkel Matthew , Wright Robert , de Vicente Juan
Published: May 2023

Magnetorheological fluids structured under precession fields are thoroughly investigated. Having complete dynamic triaxial magnetic field control, we are able to study both the structural and magnetorheological response via videomicroscopy and rheometry integration for a wide range of magnetic field configurations, once previously limited to traditional uniaxial fields. Optimal precession fields for driving the formation of more robust particle structures enhancing yield stress response are identified. It is believed that structural reinforcement comes from chain coarsening through lateral chain coalescence and particle compactness within the structures such that a lower energy configuration is found for certain field configurations. Particle level simulations supplement our understanding of lateral chain coalescence and structure strengthening.
PD-L1 methylation restricts PD-L1/PD-1 interactions to control cancer immune surveillance
Authors: Huang Changsheng , Ren Shengxiang , Chen Yaqi , Liu Anyi , Wu Qi , Jiang Tao , Lv Panjing , Song Da , Hu Fuqing , Lan Jingqing , Sun Li , Zheng Xue , Luo Xuelai , Chu Qian , Jia Keyi , Li Yan , Wang Jun , Zou Caicun , Hu Junbo , Wang Guihua
Published: May 2023

Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) have enabled some patients with cancer to experience durable, complete treatment responses; however, reliable anti–PD-(L)1 treatment response biomarkers are lacking. Our research found that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Furthermore, PD-L1 K162 methylation controlled the PD-1/PD-L1 interaction and obviously enhanced the suppression of T cell activity controlling cancer immune surveillance. We demonstrated that PD-L1 hypermethylation was the key mechanism for anti–PD-L1 therapy resistance, investigated that PD-L1 K162 methylation was a negative predictive marker for anti–PD-1 treatment in patients with non–small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti–PD-(L)1 therapy sensitivity. These findings provide insights into the regulation of the PD-1/PD-L1 pathway, identify a modification of this critical immune checkpoint, and highlight a predictive biomarker of the response to PD-1/PD-L1 blockade therapy.
CAGE sequencing reveals CFTR-dependent dysregulation of type I IFN signaling in activated cystic fibrosis macrophages
Authors: Gillan Jonathan L. , Chokshi Mithil , Hardisty Gareth R. , Clohisey Hendry Sara , Prasca-Chamorro Daniel , Robinson Nicola J. , Lasota Benjamin , Clark Richard , Murphy Lee , Whyte Moira K. B. , Baillie J. Kenneth , Davidson Donald J. , Bao Gang , Gray Robert D.
Published: May 2023

An intense, nonresolving airway inflammatory response leads to destructive lung disease in cystic fibrosis (CF). Dysregulation of macrophage immune function may be a key facet governing the progression of CF lung disease, but the underlying mechanisms are not fully understood. We used 5′ end centered transcriptome sequencing to profileP. aeruginosaLPS-activated human CF macrophages, showing that CF and non-CF macrophages deploy substantially distinct transcriptional programs at baseline and following activation. This includes a significantly blunted type I IFN signaling response in activated patient cells relative to healthy controls that was reversible upon in vitro treatment with CFTR modulators in patient cells and by CRISPR-Cas9 gene editing to correct the F508del mutation in patient-derived iPSC macrophages. These findings illustrate a previously unidentified immune defect in human CF macrophages that is CFTR dependent and reversible with CFTR modulators, thus providing new avenues in the search for effective anti-inflammatory interventions in CF.
Cellular-scale proximity labeling for recording cell spatial organization in mouse tissues
Authors: Zhang Xu , Tang Qi , Sun Jiayu , Guo Yilan , Zhang Shaoran , Liang Shuyu , Dai Peng , Chen Xing
Published: May 2023

Proximity labeling has emerged as a powerful strategy for interrogating cell-cell interactions. However, the nanometer-scale labeling radius impedes the use of current methods for indirect cell communications and makes recording cell spatial organization in tissue samples difficult. Here, we develop quinone methide–assisted identification of cell spatial organization (QMID), a chemical strategy with the labeling radius matching the cell dimension. The activating enzyme is installed on the surface of bait cells, which produces QM electrophiles that can diffuse across micrometers and label proximal prey cells independent of cell-cell contacts. In cell coculture, QMID reveals gene expression of macrophages that are regulated by spatial proximity to tumor cells. Furthermore, QMID enables labeling and isolation of proximal cells of CD4
+
and CD8
+
T cells in the mouse spleen, and subsequent single-cell RNA sequencing uncovers distinctive cell populations and gene expression patterns within the immune niches of specific T cell subtypes. QMID should facilitate dissecting cell spatial organization in various tissues.
Super-compact universal quantum logic gates with inverse-designed elements
Authors: He Lu , Liu Dongning , Gao Jingxing , Zhang Weixuan , Zhang Huizhen , Feng Xue , Huang Yidong , Cui Kaiyu , Liu Fang , Zhang Wei , Zhang Xiangdong
Published: May 2023

Integrated quantum photonic circuit is a promising platform for the realization of quantum information processing in the future. To achieve the large-scale quantum photonic circuits, the applied quantum logic gates should be as small as possible for the high-density integration on chips. Here, we report the implementation of super-compact universal quantum logic gates on silicon chips by the method of inverse design. In particular, the fabricated controlled-NOT gate and Hadamard gate are both nearly a vacuum wavelength, being the smallest optical quantum gates reported up to now. We further design the quantum circuit by cascading these fundamental gates to perform arbitrary quantum processing, where the corresponding size is about several orders smaller than that of previous quantum photonic circuits. Our study paves the way for the realization of large-scale quantum photonic chips with integrated sources and can have important applications in the field of quantum information processes.
IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation
Authors: Conrey Peyton E. , Denu Lidiya , O’Boyle Kaitlin C. , Rozich Isaiah , Green Jamal , Maslanka Jeffrey , Lubin Jean-Bernard , Duranova Tereza , Haltzman Brittany L. , Gianchetti Lauren , Oldridge Derek A. , De Luna Nina , Vella Laura A. , Allman David , Spergel Jonathan M. , Tanes Ceylan , Bittinger Kyle , Henrickson Sarah E. , Silverman Michael A.
Published: May 2023

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have been proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on a larger scale, whether the systemic and mucosal anti-commensal responses are redundant or have unique features. To address this gap in knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry and metagenomic sequencing (mFLOW-Seq) to comprehensively define which microbes induce mucosal and systemic antibodies. We coupled this approach with high-dimensional immune profiling to study a cohort of pediatric patients with SIgAD and household control siblings. We found that mucosal and systemic antibody networks cooperate to maintain homeostasis by targeting a common subset of commensal microbes. In IgA-deficiency, we find increased translocation of specific bacterial taxa associated with elevated levels of systemic IgG targeting fecal microbiota. Associated features of immune system dysregulation in IgA-deficient mice and humans included elevated levels of inflammatory cytokines, enhanced follicular CD4 T helper cell frequency and activation, and an altered CD8 T cell activation state. Although SIgAD is clinically defined by the absence of serum IgA, the symptomatology and immune dysregulation were concentrated in the SIgAD participants who were also fecal IgA deficient. These findings reveal that mucosal IgA deficiency leads to aberrant systemic exposures and immune responses to commensal microbes, which increase the likelihood of humoral and cellular immune dysregulation and symptomatic disease in patients with IgA deficiency.
Rising trend of childlessness in China: analysis of social and regional disparities with 2010 and 2020 census data
Authors: Jiang Quanbao , Zhang Cuiling , Zhuang Yaer , Jiang Yu , Zhang Xuying
Published: May 2023

Introduction

In recent decades, there has been a significant increase in childlessness. This paper analysed childlessness in China, specifically examining its socio and regional disparities.

Methods

With data from China’s 2020 population census, supplemented with data from China’s 2010 population census and 2015 inter-censual 1% population sample survey, we used a basic indicator of age-specific childlessness proportion, a decomposition method, and probability distribution models to analyse, fit and project childlessness.

Results

We presented age-specific childlessness proportions for women as a whole and by socioeconomic features, decomposition and projection results. The childlessness proportion increased markedly from 2010 to 2020, reaching 5.16% for women aged 49. The proportion is highest for city women, followed by township women, and is lowest among village women, at 6.29%, 5.50% and 3.72 % for women aged 49, respectively. The proportion for women aged 49 with high college education or above was 7.98%, and only 4.42% for women with junior high school education. The proportion also exhibits marked provincial discrepancies, and the total fertility rate is negatively correlated with childlessness at the province level. The decomposition results distinguished the different contribution of change in educational structure and change in childlessness proportion for subgroups to the total childlessness proportion change. It is projected that city women, women with high education will have higher childlessness proportion, and the proportion will further increase with the rapid increase in education level and urbanisation.

Conclusions

Childlessness has risen to a relatively high level, and varies among women with different characteristics. This should be taken into consideration in China’s countermeasures to reduce childlessness and curtail further fertility decline accordingly.
Assessment of anaesthesia workforce capacity in district and tehsil (taluka) hospitals in Sindh province of Pakistan: a survey
Authors: Khuwaja Amin , Tabassum Rafia , Soomro Ahmed , Diloo Raja , Kumar Kelash , Ahmed Jamil , Khan Fauzia
Published: May 2023

Objectives

Our objective was to determine the current availability of human resource at secondary care hospitals in Sindh province and to identify gaps in term of appropriate number of anaesthesiologists available for delivery of safe anaesthesia care.

Design

A cross-sectional survey of anaesthesia workforce.

Setting

All district and taluka hospitals in the Sindh province of Pakistan.

Participants

Administrative anaesthesia leaders in the hospitals.

Outcome measures

Standard descriptive statistics (percentages and numbers) of anaesthesia workforce in these hospitals including both full-time and part-time physician anaesthesiologists, and non-specialist physicians providing anaesthesia services as well as technician support.

Results

Only 54 (75%) hospitals had a full-time anaesthesia physician, and 32 of these had only one. Two hundred and one operating rooms were present in 72 (80%) hospitals with an average of three operating rooms/hospital.

Conclusions

This study has identified a deficit of anaesthesiology personnel in district-level and tehsil-level hospitals of Sindh province of Pakistan.
Anticipatory prescribing in community end-of-life care: systematic review and narrative synthesis of the evidence since 2017
Authors: Bowers Ben , Antunes Bárbara Costa Pereira , Etkind Simon , Hopkins Sarah A , Winterburn Isaac , Kuhn Isla , Pollock Kristian , Barclay Stephen
Published: May 2023

Background

The anticipatory prescribing of injectable medications is recommended practice in controlling distressing symptoms in the last days of life. A 2017 systematic review found practice and guidance was based on inadequate evidence. Since then, there has been considerable additional research, warranting a new review.

Aim

To review the evidence published since 2017 concerning anticipatory prescribing of injectable medications for adults at the end-of-life in the community, to inform practice and guidance.

Design

Systematic review and narrative synthesis.

Methods

Nine literature databases were searched from May 2017 to March 2022, alongside reference, citation and journal hand-searches. Gough’s Weight of Evidence framework was used to appraise included studies.

Results

Twenty-eight papers were included in the synthesis. Evidence published since 2017 shows that standardised prescribing of four medications for anticipated symptoms is commonplace in the UK; evidence of practices in other countries is limited. There is limited data on how often medications are administered in the community. Prescriptions are ‘accepted’ by family caregivers despite inadequate explanations and they generally appreciate having access to medications. Robust evidence of the clinical and cost-effectiveness of anticipatory prescribing remains absent.

Conclusion

The evidence underpinning anticipatory prescribing practice and policy remains based primarily on healthcare professionals’ perceptions that the intervention is reassuring, provides effective, timely symptom relief in the community and prevents crisis hospital admissions. There is still inadequate evidence regarding optimal medications and dose ranges, and the effectiveness of these prescriptions. Patient and family caregiver experiences of anticipatory prescriptions warrant urgent investigation.

PROSPERO registration

CRD42016052108
Is the public ready for a tobacco-free Ireland? A national survey of public knowledge and attitudes to tobacco endgame in Ireland
Authors: Cosgrave Ellen Juliet , Blake Martina , Murphy Edward , Sheridan Aishling , Doyle Frank , Kavanagh Paul
Published: May 2023

Aim

Ireland will not meet the tobacco endgame goal set in its 2013 Tobacco-Free Ireland (TFI) policy of reducing smoking prevalence to less than 5% by 2025. Public opinion on tobacco endgame, a key lever to realise this goal, is uncharted in Ireland. This study aimed to measure public knowledge and attitudes to tobacco endgame.

Methods

A telephone-administered cross-sectional survey of 1000 randomly dialled members of the general public was conducted in 2022. Prevalence of awareness, perceived achievability and support for the TFI goal and tobacco endgame measures was calculated and compared across tobacco product use status. Logistic regression identified factors independently associated with goal support.

Findings

Although TFI goal awareness was low (34.0%), support was high (74.6%), although most (60.2%) believed it achievable beyond 2025. Product-focused measures were popular while support for supply-focused measures was mixed: for example, 86.1% supported nicotine content reduction while 40.3% supported user licencing. Phasing out tobacco sales was highly supported (82.8%); for most, this was contingent on support for currently addicted users. TFI goal support was independently associated with female sex (adjusted odds ratio (aOR) 1.47, 95% CI 1.05 to 2.07), higher education (aOR 1.80, 95% CI 1.21 to 2.66) and non-tobacco product use (aOR 2.67, 95% CI 1.66 to 4.30).

Conclusions

Despite low awareness, tobacco endgame support is strong in Ireland. Public appetite for radically reducing tobacco product appeal and availability combined with public views on endgame achievability subject to extended timelines should be used to re-invigorate tobacco endgame discussion and planning in countries at risk of failing to meet declared targets.