bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of microneedling depth of penetration in management of atrophic acne scars: a split‐face comparative study
Authors: El‐Domyati Moetaz , Moftah Noha H. , Ahmed Asmaa M. , Ibrahim Michel R.
Published: December 2023

Background

Microneedling is a technique of repeated puncturing or drilling of the skin to induce repair and collagen induction. There are many reported important factors determining the efficacy of microneedling treatment. The extent of injury needed to produce the desired effect in each condition is one of these important factors.

Objectives

We designed the present split‐face comparative study to evaluate the use and effectiveness of two different depths of penetration of Dermapen needles in the management of atrophic postacne scars.

Patients and methods

The present study involved 14 subjects with atrophic postacne scars. In each patient, both sides of the face were treated with six sessions of microneedling, using Dermapen at 2‐week intervals. A split‐face study design was performed. The right (Rt) side of the face was treated with Dermapen using 2.5 mm needle length, while the left (Lt) side was treated using 1.5 mm needle length.

Results

There was a significantly better percentage of improvement of acne scars on the Rt side of the face compared to the Lt side (P = 0.02) after six sessions. Both sides of the face showed improvement of collagen bundles and elastic fibers characteristics after six sessions.

Conclusions

The use of 2.5 mm depth proved to be more effective both clinically and histologically in the management of atrophic postacne scars.
Milk fortified with chitooligosaccharide–gallic acid conjugate and its liposome: characterisation, storage stability, and in vitro digestibility
Authors: Mittal Ajay , Benjakul Soottawat , Palamae Suriya , Saetang Jirakrit , Singh Avtar
Published: December 2023

The effects of chitooligosaccharide–gallic acid conjugate (CGC) and its liposome (CGLP) at two levels (1.25 and 2.50%, w/v) on quality and shelf‐life of milk kept at 4 °C were studied. Microbial counts including total viable, pathogenic and spoilage bacteria were the lowest for CGC‐fortified milk, especially when 2.50% (w/v) was used (CGC‐2.50) than remaining samples (P < 0.05). Lower thiobarbituric acid reactive substances and peroxide values were obtained for CGC‐2.50 than other samples (P < 0.05). However, higher acidity values and decreased pH and lightness were noticed in the aforementioned sample (P < 0.05). Moreover, all fortified milk samples had higher bioactivities during in vitro digestion, in which CGC‐2.50 had the highest bioactivities (P < 0.05). Higher retention of unsaturated fatty acids content in CGC‐2.50 was obtained than other counterparts (P < 0.05). Therefore, CGC efficiently extended milk shelf‐life with high acceptability at 4 °C for a minimum of 6 days, whereas control had a shelf‐life of less than 4 days.
Twenty years of social media marketing: A systematic review, integrative framework, and future research agenda
Authors: Bartoloni Sara , Ancillai Chiara
Published: December 2023

Social media has been around for 20 years and has profoundly affected the dynamics of interactions between companies and customers. Studies have increasingly focused on how firms effectively use social media in their marketing strategies. However, the literature appears highly fragmented. Scholars have tended to investigate individual facets of social media marketing (SMM) behaviours, adopting a narrow perspective on their antecedents and outcomes. This approach hinders a comprehensive understanding of the overall phenomenon. Against this background, we conducted a systematic literature review (SLR) of 169 articles to develop a causal‐chain framework based on inputs, contingency factors, and outputs to illustrate the interrelationships among different research constructs explored so far. This framework contributes to overcoming the isolated perspectives of firms’ SMM that have characterized the extant knowledge, thus offering clarity and an overarching view of SMM in firms. The findings also provide concrete guidance for future research endeavours in this area.
Medications and cognitive risk in Aboriginal primary care: a cross‐sectional study
Authors: Holdaway Marycarol , Hyde Zoë , Hughson Jo‐anne , Malay Roslyn , Stafford Andrew , Fulford Kate , Radford Kylie , Flicker Leon , Smith Kate , Pond Dimity , Russell Sarah , Atkinson David , Blackberry Irene , LoGiudice Dina
Published: December 2023

Background

Aboriginal and Torres Strait Islander people are ageing with high rates of comorbidity, yet little is known about suboptimal prescribing in this population.

Aim

The prevalence of potentially suboptimal prescribing and associated risk factors were investigated among older patients attending primary care through Aboriginal Community Controlled Health Services (ACCHSs).

Methods

Medical records of 420 systematically selected patients aged ≥50 years attending urban, rural and remote health services were audited. Polypharmacy (≥ 5 prescribed medications), potentially inappropriate medications (PIMs) as per Beers Criteria and anticholinergic burden (ACB) were estimated and associated risk factors were explored with logistic regression.

Results

The prevalence of polypharmacy, PIMs and ACB score ≥3 was 43%, 18% and 12% respectively. In multivariable logistic regression analyses, polypharmacy was less likely in rural (odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.24–0.77) compared to urban patients, and more likely in those with heart disease (OR = 2.62, 95% CI = 1.62–4.25), atrial fibrillation (OR = 4.25, 95% CI = 1.08–16.81), hypertension (OR = 2.14, 95% CI = 1.34–3.44), diabetes (OR = 2.72, 95% CI = 1.69–4.39) or depression (OR = 1.91, 95% CI = 1.19–3.06). PIMs were more frequent in females (OR = 1.88, 95% CI = 1.03–3.42) and less frequent in rural (OR = 0.41, 95% CI = 0.19–0.85) and remote (OR = 0.58, 95% CI = 0.29–1.18) patients. Factors associated with PIMs were kidney disease (OR = 2.60, 95% CI = 1.37–4.92), urinary incontinence (OR = 3.00, 95% CI = 1.02–8.83), depression (OR = 2.67, 95% CI = 1.50–4.77), heavy alcohol use (OR = 2.83, 95% CI = 1.39–5.75) and subjective cognitive concerns (OR = 2.69, 95% CI = 1.31–5.52). High ACB was less common in rural (OR = 0.10, 95% CI = 0.03–0.34) and remote (OR = 0.51, 95% CI = 0.25–1.04) patients and more common in those with kidney disease (OR = 3.07, 95% CI = 1.50–6.30) or depression (OR = 3.32, 95% CI = 1.70–6.47).

Conclusion

Associations between potentially suboptimal prescribing and depression or cognitive concerns highlight the importance of considering medication review and deprescribing for these patients.
Dimensions of young children's toothbrushing resistance: A qualitative content analysis of discussions on the online parenting forum Mumsnet
Authors: Kettle Jennifer , Marshman Zoe
Published: December 2023

Background

Young children's resistant behaviour is a barrier to parental‐supervised brushing. Discussions on online parenting forums offer an insight into parental experiences, behaviour and attitudes. Analysing these discussions also demonstrates how dental advice is represented and potentially resisted.

Aim

To analyse how young children's toothbrushing resistance is discussed on an online parenting forum.

Design

Qualitative content analysis of threads on toothbrushing resistance retrieved from the UK parenting forum Mumsnet.

Results

A search was carried out on Mumsnet in April 2022. Overall, 204 relevant threads were identified and analysed. A coding frame was developed. Posters interacted by discussing their experiences of resistance, asking for advice, making suggestions and being both supportive and critical. Thirty‐seven strategies for addressing resistance were identified. Discussions reflected attitudes and concerns relating to young children and toothbrushing resistance, including the idea brushing should be ‘non‐negotiable’. A key issue was the acceptability of physical force or restraint to achieve adequate brushing. Posters invoked dental authority to support their views.

Conclusion

Understanding how toothbrushing resistance is discussed on a parenting forum helps establish what information and advice is shared, and highlights attitudes and concerns that shape how this problem is approached.
A non‐verbal teaching behaviour analysis for improving pointing out gestures: The case of asynchronous video lecture analysis using deep learning
Authors: Yoon Ho Young , Kang Seokmin , Kim Sungyeun
Published: December 2023

Background

Research into enhancing the effectiveness of information delivery in asynchronous video lectures remains sparse. This study analyzes the nonverbal teaching behaviours in asynchronous online videos, drawing comparisons between pre‐service and in‐service teachers (ITs).

Objectives

This research primarily aims to juxtapose the nonverbal teaching behaviours, such as arm extensions and body orientation, utilized by pre‐service teachers (PTs) and ITs within asynchronous online videos.

Methods

Asynchronous video lectures from four pre‐service and four ITs across four diverse subject topics were scrutinized. Leveraging deep learning technology, teachers' poses during their instruction towards a video camera were quantified, with a particular focus on arm stretch range and body orientation in relation to the subject being taught.

Results

The findings revealed that PTs were deficient in effectively employing pointing gestures. Their arm stretches and body orientation towards the board were not differentiated across subjects. Conversely, ITs demonstrated subject‐specific variations in their arm extension and body orientation, signalling their effective strategies for knowledge dissemination.

Conclusions and Discussion

This study emphasizes the importance of assessing nonverbal teaching behaviours in the development of effective instructional training. It accentuates the need for nonverbal communication and subject‐specific teaching strategy training in PTs. Future investigations could broaden their scope to include larger sample sizes and expanded subject areas to discern more comprehensive trends in nonverbal teaching behaviours.
circELP2 reverse‐splicing biogenesis and function as a pro‐fibrogenic factor by targeting mitochondrial quality control pathway
Authors: Zhang Songzi , Tu Diwei , Liu Weili , Li Ruiqiong , Jiang Mengqi , Yuan Xinglong , Luan Jianlin , Li Hongbo , Lv Changjun , Song Xiaodong
Published: December 2023

Idiopathic pulmonary fibrosis (IPF) is considered as a chronic, fibrosing interstitial pneumonia with unknown mechanism. The present work aimed to explore the function, biogenesis and regulatory mechanism of circELP2 in pulmonary fibrosis and evaluate the value of blocking circELP2‐medicated signal pathway for IPF treatment. The results showed that heterogeneous nuclear ribonucleoprotein L initiated reverse splicing of circELP2 resulting in the increase of circELP2 generation. The biogenetic circELP2 activated the abnormal proliferation and migration of fibroblast and extracellular matrix deposition to promote pulmonary fibrogenesis. Mechanistic studies demonstrated that cytoplasmic circELP2 sponged miR‐630 to increase transcriptional co‐activators Yes‐associated protein 1 (YAP1) and transcriptional co‐activator with PDZ‐binding motif (TAZ). Then, YAP1/TAZ bound to the promoter regions of their target genes, such as mTOR, Raptor and mLST8, which in turn activated or inhibited the genes expression in mitochondrial quality control pathway. Finally, the overexpressed circELP2 and miR‐630 mimic were packaged into adenovirus vector for spraying into the mice lung to evaluate therapeutic effect of blocking circELP2‐miR‐630‐YAP1/TAZ‐mitochondrial quality control pathway in vivo. In conclusion, blocking circELP2‐medicated pathway can alleviate pulmonary fibrosis, and circELP2 may be a potential target to treat lung fibrosis.
Exposure to prenatal infection and the development of internalizing and externalizing problems in children: a longitudinal population‐based study
Authors: Suleri Anna , Rommel Anna‐Sophie , Neumann Alexander , Luo Mannan , Hillegers Manon , de Witte Lotje , Bergink Veerle , Cecil Charlotte A. M.
Published: December 2023

Background

A large body of work has reported a link between prenatal exposure to infection and increased psychiatric risk in offspring. However, studies to date have focused primarily on exposure to severe prenatal infections and/or individual psychiatric diagnoses in clinical samples, typically measured at single time points, and without accounting for important genetic and environmental confounders. In this study, we investigated whether exposure to common infections during pregnancy is prospectively associated with repeatedly assessed child psychiatric symptoms in a large population‐based study.

Methods

Our study was embedded in a prospective pregnancy cohort (Generation R; n = 3,598 mother–child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. Child total, internalizing, and externalizing problems were assessed repeatedly using the parent‐rated Child Behavioral Checklist (average age: 1.5, 3, 6, 10, and 14 years). Linear mixed‐effects models were run adjusting for a range of confounders, including child polygenic scores for psychopathology, maternal chronic illness, birth complications, and infections during childhood. We also investigated trimester‐specific effects and child sex as a potential moderator.

Results

Prenatal exposure to infections was associated with higher child total, internalizing, and externalizing problems, showing temporally persistent effects, even after adjusting for important genetic and environmental confounders. We found no evidence that prenatal infections were associated with changes in child psychiatric symptoms over time. Moreover, in our trimester‐specific analysis, we did not find evidence of significant timing effects of prenatal infection on child psychiatric symptoms. No interactions with child sex were identified.

Conclusions

Our research adds to evidence that common prenatal infections may be a risk factor for psychiatric symptoms in children. We also extend previous findings by showing that these associations are present early on, and that rather than changing over time, they persist into adolescence. However, unmeasured confounding may still explain in part these associations. In the future, employing more advanced causal inference designs will be crucial to establishing the degree to which these effects are causal.
Consistency of convolutional neural networks in dermoscopic melanoma recognition: A prospective real‐world study about the pitfalls of augmented intelligence
Authors: Goessinger E. V. , Cerminara S. E. , Mueller A. M. , Gottfrois P. , Huber S. , Amaral M. , Wenz F. , Kostner L. , Weiss L. , Kunz M. , Maul J.‐T. , Wespi S. , Broman E. , Kaufmann S. , Patpanathapillai V. , Treyer I. , Navarini A. A. , Maul L. V.
Published: December 2023

Background

Deep‐learning convolutional neural networks (CNNs) have outperformed even experienced dermatologists in dermoscopic melanoma detection under controlled conditions. It remains unexplored how real‐world dermoscopic image transformations affect CNN robustness.

Objectives

To investigate the consistency of melanoma risk assessment by two commercially available CNNs to help formulate recommendations for current clinical use.

Methods

A comparative cohort study was conducted from January to July 2022 at the Department of Dermatology, University Hospital Basel. Five dermoscopic images of 116 different lesions on the torso of 66 patients were captured consecutively by the same operator without deliberate rotation. Classification was performed by two CNNs (CNN‐1/CNN‐2). Lesions were divided into four subgroups based on their initial risk scoring and clinical dignity assessment. Reliability was assessed by variation and intraclass correlation coefficients. Excisions were performed for melanoma suspicion or two consecutively elevated CNN risk scores, and benign lesions were confirmed by expert consensus (n = 3).

Results

117 repeated image series of 116 melanocytic lesions (2 melanomas, 16 dysplastic naevi, 29 naevi, 1 solar lentigo, 1 suspicious and 67 benign) were classified. CNN‐1 demonstrated superior measurement repeatability for clinically benign lesions with an initial malignant risk score (mean variation coefficient (mvc): CNN‐1: 49.5(±34.3)%; CNN‐2: 71.4(±22.5)%; p = 0.03), while CNN‐2 outperformed for clinically benign lesions with benign scoring (mvc: CNN‐1: 49.7(±22.7)%; CNN‐2: 23.8(±29.3)%; p = 0.002). Both systems exhibited lowest score consistency for lesions with an initial malignant risk score and benign assessment. In this context, averaging three initial risk scores achieved highest sensitivity of dignity assessment (CNN‐1: 94%; CNN‐2: 89%). Intraclass correlation coefficients indicated ‘moderate’‐to‐‘good’ reliability for both systems (CNN‐1: 0.80, 95% CI:0.71–0.87, p < 0.001; CNN‐2: 0.67, 95% CI:0.55–0.77, p < 0.001).

Conclusions

Potential user‐induced image changes can significantly influence CNN classification. For clinical application, we recommend using the average of three initial risk scores. Furthermore, we advocate for CNN robustness optimization by cross‐validation with repeated image sets.

Trial Registration

ClinicalTrials.gov (NCT04605822).
Parasitism success of Microplitis manilae (Hymenoptera: Braconidae) on different diet‐fed Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae
Authors: Tian Shuang , Di Xue‐Yuan , Yan Bin , Ren Peng , Wu Hui‐Zi , Yang Mao‐Fa
Published: December 2023

Efficient rearing is necessary for the successful biological control of pests. The braconid wasp, Microplitis manilae, is a natural solitary parasitoid of larval Spodoptera frugiperda. However, the effect of the host diet on the parasitism success of M. manilae on S. frugiperda larvae remains unclear. Here, we determined the parasitism rate, oviposition, eclosion rate, developmental period and offspring sex ratio of M. manilae parasitizing S. frugiperda fed with fresh corn leaves or an artificial diet. M. manilae parasitizing the corn leaf‐fed S. frugiperda larvae exhibited a significantly higher parasitism rate (40%), oviposition (62.50 eggs/female) and eclosion rate (81.38%) than the wasp parasitizing the artificial diet‐fed S. frugiperda larvae (22%, 38.33 eggs/female, and 58.73%, respectively). Furthermore, M. manilae parasitizing the corn leaf‐fed S. frugiperda larvae exhibited a significantly shorter developmental period (16.35 days) and lower sex ratio (1.17) than the wasp parasitizing the artificial diet‐fed S. frugiperda larvae (18.00 and 2.15 days, respectively). Overall, M. manilae exhibited better parasitic success on corn leaf‐fed S. frugiperda larvae than on artificial diet‐fed S. frugiperda larvae. Therefore, using fresh corn leaf‐fed S. frugiperda is the most suitable strategy for mass‐rearing M. manilae for pest biocontrol. Our findings suggest M. manilae as an effective biocontrol candidate for controlling S. frugiperda in corn fields.
In‐depth study of Wood's lamp examination combined with reflective confocal laser scanning microscopy for the guidance of vitiligo staging and treatment
Authors: Hou Yongqing , Wei Zijia , Jiang Qian , Chen Hongying , Chen Liuqing , Wu Jiyuan
Published: December 2023

Background

Both Wood's lamp and reflective confidential laser scanning microcopy are helpful for the diagnosis and treatment of vitiligo. However, there is few research that contains large samples and consistent observations.

Aims

To analyze the characteristics of Wood's lamp images and reflectance confocal microscopy (RCM) images of vitiligo lesions and to evaluate their significance in vitiligo staging.

Methods

We analyzed the characteristics of RCM images, Wood's lamp images, the vitiligo disease activity (VIDA) score, and clinical features to guide vitiligo staging and treatment.

Results

The expert consensus based on the clinical features, VIDA score, Wood's lamp findings, and isomorphic response was consistent with the Wood's lamp findings (χ2 = 3.63, p > 0.05) and RCM findings (χ2 = 3.60, p > 0.05) in diagnosing vitiligo and assessing the disease stage. There was a correlation between the three lesion grades based on the Wood's lamp findings and the stage of vitiligo (p < 0.01). Lesions that appeared porcelain white under the Wood's lamp were in the slowly progressive stage; lesions that appeared gray‐white or trichromatic under the Wood's lamp were in the rapidly progressive stage; lesions with clear borders under the Wood's lamp needed further analysis by RCM for the stage to be determined; lesions with blurred borders under the Wood's lamp were in the rapidly progressive stage; lesions that were visible under the naked eye and under the Wood's lamp were in the rapidly progressive stage.

Conclusion

The study demonstrates a reliable correlation between the findings of RCM (a sophisticated expensive tool) and Wood's lamp examination (a simple, readily available, inexpensive tool) in the assessment of the disease activity of vitiligo lesions.
Board‐level governance and corporate social responsibility: A meta‐analytic review
Authors: Hussain Nazim , Khan Sana Akbar , Nguyen Duc Khuong , Stocchetti Andrea , Corbet Shaen
Published: December 2023

Board‐level corporate governance (CG) is an effective route to developing sustained ethical behavior, helping firms to meet emerging accountability challenges and international expectations of corporate performance. In recent times, researchers have extensively studied the relationships between various board‐level governance mechanisms and corporate social responsibility (CSR) outcomes; however, results vary substantially. This study addresses the existing heterogeneity in the literature by systematically synthesizing 89 empirical studies on the board governance‐CSR nexus using meta‐analyses using random effect models. Results indicate that most governance mechanisms are strongly associated with CSR disclosure. On the contrary, only a few governance mechanisms are found to be significantly associated with CSR performance, suggesting that not all governance mechanisms are equally effective for performance and disclosure. However, board size and the presence of CSR committee on board are the closest predictors of both CSR outcomes. Additionally, our analysis of the moderating effect of study characteristics shows that coverage period, geographical setting, and measurement of CSR generate variability in existing findings. Our synthesis of the extant literature identifies a theoretical gap, clarifies the board CG‐CSR relationship, and proposes future research directions and guidelines within the field.
Monopsony Power and Upstream Innovation*
Authors: Parra Álvaro , Marshall Guillermo
Published: December 2023

How does a monopsonist incentivize its supplier to innovate? By decreasing the short‐run profit of the supplier, the monopsonist can increase the supplier's incentive to invest in R&D by lessening the supplier's Arrow's replacement effect. The monopsonist engages in this practice despite a distortion in its trade volume with the supplier that causes inefficiency. We discuss implications for the boundaries of the firm.
Distribution of rapid HCV antibody self‐test kits via needle/syringe dispensing machines: Implementation and evaluation of the Vend‐C pilot study in Melbourne, Australia
Authors: O'Keefe Daniel , Jacka David , Douglass Caitlin , Gunn Jack , Stoove Mark , Crawford Sione , Bryant Mellissa , Higgs Peter , Dietze Paul , Hellard Margaret
Published: December 2023

Recent guidance from the World Health Organization strongly recommended hepatitis C virus (HCV) self‐testing. We implemented the Vend‐C pilot study to explore the effectiveness and feasibility of distributing rapid HCV antibody self‐test kits to people who inject drugs via needle/syringe dispensing machines (SDMs). Over a 51‐day study period between August and September 2022, we distributed HCV antibody self‐test kits via two SDMs. During the study period, 63 self‐test kits were dispensed, averaging 1.2 self‐test kits per day. Our access methods for evaluation questionnaires failed to attract participants (n = 4). We implemented the Vend‐C pilot study in direct response to recent WHO recommendations. While self‐test kits were effectively distributed from the two SDMs, our evaluation methodology failed. Consequently, we cannot determine the success of linkage to care. Even so, with HCV treatment numbers dropping in Australia, innovative engagement solutions are needed, and considering the number of self‐test kits provided in our pilot, the model could have an important future place in HCV elimination efforts.
The impact of hepatitis B and C positive serologies on the outcomes of non‐hepatic solid organ transplantation in the United States
Authors: Alqahtani Saleh A. , Stepanova Maria , Al Shabeeb Reem , Eberly Kathrine Luz , Ong Janus , Younossi Zobair M.
Published: December 2023

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non‐hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post‐transplant outcomes in patients with HBV or HCV positivity receiving non‐hepatic solid‐state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006–2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post‐transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post‐transplant survival between lung transplant recipients with vs. without anti‐HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post‐transplant mortality (all p < .01). Similarly, there was higher post‐transplant mortality in kidney transplant recipients with HCV+ (1‐year: 6% vs. 3%; 5‐year: 21% vs. 13%; 10‐year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post‐kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12–1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post‐transplant outcomes in non‐hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post‐transplant mortality.
The role of dacarbazine and temozolomide therapy after treatment with immune checkpoint inhibitors in malignant melanoma patients: A case series and meta‐analysis
Authors: Rydén Viktoria , El‐Naggar Ali Inan , Koliadi Anthoula , Ladjevardi Cecilia Olsson , Digkas Evangelos , Valachis Antonios , Ullenhag Gustav J.
Published: December 2023

Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta‐analysis. Thirty‐five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real‐world progression‐free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta‐analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real‐world response rate to chemotherapy for the prior‐CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04–4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.
Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study
Authors: Deng Ling , Wang Hai‐Yun , Hu Chun‐Fang , Liu Xiao‐Yun , Jiang Kuntai , Yong Juan‐Juan , Wu Xiao‐Yan , Guo Kai‐Hua , Wang Fang
Published: December 2023

Primary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture‐based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co‐occurred with KIT mutation and amplification. The most common pathways affected were the mitogen‐activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression‐free survival (hazard ratio [HR] = 5.14, 95% confidence interval [CI] = 1.32–19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22–15.30). Treatment with immune‐checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01–0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs.
A longitudinal study of the effect of visuomotor learning on functional brain connectivity
Authors: Wang Kuo‐Pin , Yu Chien‐Lin , Shen Cheng , Schack Thomas , Hung Tsung‐Min
Published: December 2023

Neural adaptation in the frontoparietal and motor cortex–sensorimotor circuits is crucial for acquiring visuomotor skills. However, the specific nature of highly dynamic neural connectivity in these circuits during the acquisition of visuomotor skills remains unclear. To achieve a more comprehensive understanding of the relationship between acquisition of visuomotor skills and neural connectivity, we used electroencephalographic coherence to capture highly dynamic nature of neural connectivity. We recruited 60 male novices who were randomly assigned to either the experimental group (EG) or the control group (CG). Participants in EG were asked to engage in repeated putting practice, but CG did not engage in golf practice. In addition, we analyzed the connectivity by using 8–13 Hz imaginary inter‐site phase coherence in the frontoparietal networks (Fz‐P3 and Fz‐P4) and the motor cortex–sensorimotor networks (Cz‐C3 and Cz‐C4) during a golf putting task. To gain a deeper understanding of the dynamic nature of learning trajectories, we compared data at three time points: baseline (T1), 50% improvement from baseline (T2), and 100% improvement from baseline (T3). The results primarily focused on EG, an inverted U‐shaped coherence curve was observed in the connectivity of the left motor cortex–sensorimotor circuit, whereas an increase in the connectivity of the right frontoparietal circuit from T2 to T3 was revealed. These results imply that the dynamics of cortico‐cortical communication, particularly involving the left motor cortex–sensorimotor and frontal‐left parietal circuits. In addition, our findings partially support Hikosaka et al.'s model and provide additional insight into the specific role of these circuits in visuomotor learning.
A human rights‐based approach to climate injustices at the local, national, and international levels: Program and policy recommendations
Authors: Levy Sheri R. , Gopang Meroona , Ramírez Luisa , Bernardo Allan B. I. , Ruck Martin D. , Sternisko Anni
Published: December 2023

The climate crisis threatens and violates human rights to development, education, food, health, housing, life, meaningful and informed participation, self‐determination, and water. Climate injustices refer to how some communities are shouldering the disproportionate brunt of the negative effects of climate change while being the least responsible. With a human rights‐based approach focused on protection and participation rights, this paper reviews climate injustices based on age, disability, ethnicity, gender identity, geography, income, Indigenous identity, migratory status, race, refugee and internally displaced status, and their intersections. Policy recommendations include increasing climate education, utilizing disaggregated data, and expanding mental health services. Cross‐cutting themes throughout the paper are that climate change is interconnected with other crises, thereby compounding inequalities, and that a diversity of interdisciplinary and international perspectives and knowledge centered on the voices of frontline communities are essential for addressing the climate crisis.
The role of between‐group competition in children's within‐group merit‐based resource allocation
Authors: Xiao Xue , Wang Qian , Li Yanfang
Published: December 2023

The present study tested how 5‐ to 6‐year‐old and 7‐ to 8‐year‐old children allocate with in‐group collaborators according to merit in the context of external between‐group competition. Children (N = 310) first were asked to collaborate with a high‐ or low‐merit partner to complete an intergroup game in the form of competition (further divided into win and lose conditions) or noncompetition. Afterward, they were asked to allocate, reason about, and express their expected allocations toward the in‐group collaborator. We found that 5–6‐year‐olds allocated meritoriously with collaborators in the first‐party context. In contrast, 7–8‐year‐olds were affected by external between‐group competition. Specifically, compared with the noncompetitive condition, 7–8‐year‐olds conducted equal or roughly equal allocations with the in‐group collaborator and referenced Equality and Affiliation more frequently in the win and lose conditions. Furthermore, both 5–6‐year‐olds and 7–8‐year‐olds expected teachers to allocate meritoriously across the win, lose and noncompetitive conditions, indicating that they realized that social norms require them to make allocations based on merit rather than social relationships. The findings suggest that with age, children weighed the moral concerns of merit and the social concerns of in‐group harmony when determining the allocation of resources.
How the media framed the COVID‐19 crisis on Native Nations: A case comparison ofThe New York Timesand theNavajo Times
Authors: Camarillo Earlene , Kunze Stefanie , Pollard Charlie
Published: December 2023

Objective

This article examines how the limited national media reporting covered the pandemic in American Indian communities across the United States, specifically the Diné (Navajo) Nation, and whether and how this coverage differs from American Indian news sources.

Methods

This article compares coverage related to COVID‐19 byThe New York Times(NYT) with coverage by theNavajo Times(NT), a Diné newspaper. The authors compiled their own database of news‐based articles published by theNYTand theNTcovering the pandemic and its impact on Native Nations between January 1, 2020, and September 30, 2020, and conducted a comparative content analysis of these articles.

Results

While coverage was limited, theNYTarticles highlight social inequities that settler colonialism and federal Indian law have fostered in the past and present, the cultural backdrop, which contributed to greater adverse impacts from COVID‐19. However, coverage differs from theNTin important ways, particularly when considering the distinction between the Navajo Nation as a bureaucratic entity versus the Diné people, the framing of Native peoples as adaptive, and Indigenous investment in future creation.

Conclusions

TheNTwas more nuanced in its coverage of stories of the impact of COVID‐19 on American Indian communities as compared to theNYT.
MHC‐DRB alleles with amino acids Val11, Phe13, and the shared epitopes promote collagen‐induced arthritis and a rapid IgG1 response in Filipino cynomolgus macaques
Authors: Ishigaki Hirohito , Ito Sayaka , Sasamura Takako , Ishida Hideaki , Nakayama Misako , Nguyen Cong Thanh , Kinoshita Takaaki , Suzuki Shingo , Iwatani Chizuru , Tsuchiya Hideaki , Yamanaka Hisashi , Kulski Jerzy K. , Itoh Yasushi , Shiina Takashi
Published: December 2023

Macaques are useful animal models for studying the pathogenesis of rheumatoid arthritis (RA) and the development of anti‐rheumatic drugs. The purpose of this study was to identify the major histocompatibility complex (MHC) polymorphisms associated with the pathology of collagen‐induced arthritis (CIA) and anti‐collagen IgG induction in a cynomolgus macaque model, as MHC polymorphisms affect the onset of CIA in other animal models. Nine female Filipino cynomolgus macaques were immunized with bovine type II collagen (b‐CII) to induce CIA, which was diagnosed clinically by scoring the symptoms of joint swelling over 9 weeks. MHC polymorphisms and anti‐b‐CII antibody titers were compared between symptomatic and asymptomatic macaques. Four of 9 (44%) macaques were defined as the CIA‐affected group. Anti‐b‐CII IgG in the affected group increased in titer approximately 3 weeks earlier compared with the asymptomatic group. The mean plasma IgG1 titer in the CIA‐affected group was significantly higher (p < 0.05) than that of the asymptomatic group. Furthermore, the cynomolgus macaque MHC (Mafa)‐DRB1*10:05 or Mafa‐DRB1*10:07 alleles, which contain the well‐documented RA‐susceptibility five amino acid sequence known as the shared epitope (SE) in positions 70 to 74, with valine at position 11 (Val11, V11) and phenylalanine at position 13 (Phe13, F13), were detected in the affected group. In contrast, no MHC polymorphisms specific to the asymptomatic group were identified. In conclusion, the presence of V11 and F13 along with SE in the MHC‐DRB1 alleles seems essential for the production of IgG1 and the rapid induction of severe CIA in female Filipino cynomolgus macaques.
The novel HLA‐C*17:69 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: Wang Gang‐Feng , An Lin , Ding Pei‐Pei , Xue Han‐Chun , Yang Li‐Jie
Published: December 2023

HLA‐C*17:69 differs from HLA‐C*17:01:01:02 by one nucleotide in exon 4.
Characterization of novel HLA‐A*24:608N allele discovered in Koreans
Authors: Jeong In Hwa , Lee Jong Kwon , Kwon Won Kyung , Song Eun Young , Kim Kyeong‐Hee , Lee Jina , Jung Sunmi , Jeong Mijeong , Park June‐Woo , Kang Eun Suk
Published: December 2023

A novel null HLA‐A*24 allele, HLA‐A*24:608N, was identified in five Korean subjects including three from a family and two separate individuals. This study was performed to discern its immunological function in transplantation settings. Because this null variant had deletions of approximately 12 k base pairs from intron 3 to 3′ end of the HLA‐A gene, low resolution HLA typing and amplicon‐based next generation sequencing (NGS) typing methods had failed to assign it. Hybrid capture‐based NGS method confirmed that this novel variant had a large deletion. T‐lymphocyte crossmatching by complement‐dependent lymphocytotoxicity and flow cytometry with a serum consisting anti‐HLA‐A24 antibody revealed negative results, implying that an individual with this allele would not carry a functioning A24 antigen. These findings highlight the importance of identifying a null HLA allele by employing appropriate molecular method and providing expected crossmatching outcomes in a real‐world transplantation setting.
Discovery of the HLA‐DQB1*06:465 allele, a variant of HLA‐DQB1*06:04:01:01
Authors: Yang John Jeongseok , Oh Heung‐Bum
Published: December 2023

HLA‐DQB1*06:465 differs from HLA‐DQB1*06:04:01:01 by a non‐synonymous nucleotide substitution in codon 38.
Impact of an ultrasensitive Cytomegalovirus quantitative nucleic acid test on Cytomegalovirus detection and therapy in renal transplant recipients
Authors: Beechar Vivek B. , Pouch Stephanie M. , Phadke Varun K. , Karadkhele Geeta , Larsen Christian P. , Woodworth Michael H.
Published: December 2023

Background

Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR‐based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision‐making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia.

Methods

We conducted a single‐center cohort study contrasting RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ >300 IU/mL) with those monitored with a more sensitive qNAT (LLOQ >35 IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R−: high risk; any R+: moderate risk). CMV viral load monitoring was performed monthly post transplantation, with the primary outcomes being time to CMV DNAemia and its duration.

Results

Total 1382 patients were analyzed from 2014 to 2016 and 2019 to 2021. Moderate‐risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR: 1.95, 95% confidence interval [CI]: 1.55–2.46) and an average of 24 (95% CI: 16.40–31.98) additional days of DNAemia. There was no difference in CMV end‐organ disease or 1‐year all‐cause mortality between moderate‐risk RTRs.

Conclusions

The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate‐risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs.

Key Summary

The use of ultrasensitive CMV qNAT assays in moderate‐risk CMV renal transplant recipients is associated with earlier detection and longer durations of CMV DNAemia without impacting CMV end‐organ disease or 1‐year mortality.

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Nested Selves: Self‐Organization and Shared Markov Blankets in Prenatal Development in Humans
Authors: Ciaunica Anna , Levin Michael , Rosas Fernando E. , Friston Karl
Published: December 2023

The immune system is a central component of organismic function in humans. This paper addresses self‐organization of biological systems in relation to—and nested within—other biological systems in pregnancy. Pregnancy constitutes a fundamental state for human embodiment and a key step in the evolution and conservation of our species. While not all humans can be pregnant, our initial state of emerging and growing within another person's body is universal. Hence, the pregnant state does not concern some individuals but all individuals. Indeed, the hierarchical relationship in pregnancy reflects an even earlier autopoietic process in the embryo by which the number of individuals in a single blastoderm is dynamically determined by cell– interactions. The relationship and the interactions between the two self‐organizing systems during pregnancy may play a pivotal role in understanding the nature of biological self‐organization per se in humans. Specifically, we consider the role of the immune system in biological self‐organization in addition to neural/brain systems that furnish us with a sense of self. We examine the complex case of pregnancy, whereby two immune systems need to negotiate the exchange of resources and information in order to maintain viable self‐regulation of nested systems. We conclude with a proposal for the mechanisms—that scaffold the complex relationship between two self‐organising systems in pregnancy—through the lens of the Active Inference, with a focus on shared Markov blankets.
The kiwifruit amyloplast proteome (kfALP): a resource to better understand the mechanisms underlying amyloplast biogenesis and differentiation
Authors: Li Ang , Lin Jiajia , Zeng Zhebin , Deng Zhiping , Tan Jinjuan , Chen Xiaoya , Ding Gang , Zhu Man , Xu Bin , Atkinson Ross G. , Nieuwenhuizen Niels J. , Ampomah‐Dwamena Charles , Cheng Yunjiang , Deng Xiuxin , Zeng Yunliu
Published: December 2023

The biogenesis and differentiation (B&D) of amyloplasts contributes to fruit flavor and color. Here, remodeling of starch granules, thylakoids and plastoglobules was observed during development and ripening in two kiwifruit (Actinidia spp.) cultivars – yellow‐fleshed ‘Hort16A’ and green‐fleshed ‘Hayward’. A protocol was developed to purify starch‐containing plastids with a high degree of intactness, and amyloplast B&D was studied using label‐free‐based quantitative proteomic analyses in both cultivars. Over 3000 amyloplast‐localized proteins were identified, of which >98% were quantified and defined as the kfALP (kiwifruit amyloplast proteome). The kfALP data were validated by Tandem‐Mass‐Tag (TMT) labeled proteomics in ‘Hort16A’. Analysis of the proteomic data across development and ripening revealed: 1) a conserved increase in the abundance of proteins participating in starch synthesis/degradation during both amyloplast B&D; 2) up‐regulation of proteins for chlorophyll degradation and of plastoglobule‐localized proteins associated with chloroplast breakdown and plastoglobule formation during amyloplast differentiation; 3) constitutive expression of proteins involved in ATP supply and protein import during amyloplast B&D. Interestingly, two different pathways of amyloplast B&D were observed in the two cultivars. In ‘Hayward’, significant increases in abundance of photosynthetic‐ and tetrapyrrole metabolism‐related proteins were observed, but the opposite trend was observed in ‘Hort16A’. In conclusion, analysis of the kfALP provides new insights into the potential mechanisms underlying amyloplast B&D with relevance to key fruit quality traits in contrasting kiwifruit cultivars.