bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating indigenous knowledge and rural tourism in Kongthong, the “whistling village” of India
Authors: Dixit Saurabh Kumar , Langstieh Kimberley Camelia S. , Abraham Abijith
Published: August 2022

Purpose

This paper aims to derive insights from Kongthong village, popularly known as the “whistling village,” a low-key rural tourism destination that has often gone under the radar. As an upcoming rural tourism destination, mothers create a unique tune for their children, ensuring that their identity remains unique. This is because the residents of Kongthong have two names: an official name and another in the form of a whistled tune. The primary objective of this study is to better understand the rural tourism activities at Kongthong and to explore the symbiotic relationship between indigenous cultural practices and holistic development through tourism.

Design/methodology/approach

The study uses an ethnographic approach wherein the researchers conducted in-depth interviews and group discussions. The study respondents are the village elders, youth, men and women across different age groups. The various governing bodies act as secondary data sources concerning tourism and development.

Findings

The study observes that rural tourism activities in Kongthong go hand in hand with understanding indigenous knowledge. The governing bodies and the local community are on the right path to achieving potential growth and preserving the village as a holistic rural tourist destination.

Originality/value

Rural tourism in Kongthong highlights the traditional practices of the Khasi community. Owing to this, Kongthong was nominated for the United Nations World Tourism Organization (UNWTO) best tourism village by the Government of India as it showcases local culture through social, economic and political elements at the destination that add value to a tourism product.
Clinical features and antimicrobial treatment of skin infections caused by Panton‐Valentine leukocidin‐positive methicillin‐resistant Staphylococcus aureus
Authors: Sugawara‐Mikami Mariko , Kaneko Hiroshi , Sasaki Hiroaki , Sagawa Nobuko , Kambara Takeshi , Nakaminami Hidemasa
Published: August 2022

Skin infections caused by Panton‐Valentine leukocidin (PVL)‐positive methicillin‐resistant Staphylococcus aureus (MRSA), especially the USA300 clone, have been increasing in Japan. To prevent an epidemic of PVL‐positive MRSA, rapid diagnosis and effective antimicrobial therapy are essential. However, the clinical features of, and antimicrobial efficacy against, these skin infections are not well understood in Japan. Here, we report 10 cases of skin infections caused by PVL‐positive MRSA that presented over a two‐year period in our clinic. Genetic analyses revealed that 90% of the PVL‐positive MRSA strains were identified as USA300 and its related clones. Notably, 70% of the patients had atopic dermatitis (AD) as an underlying disease. Average durations of antimicrobial therapy for AD patients (10.6 weeks) were 2.9‐fold longer than those for non‐AD patients (3.7 weeks). However, all cases were improved by a long‐term course of fosfomycin, minocycline, doxycycline, and/or rifampicin. Our data suggest that AD may be an important risk factor for intractable skin infections caused by PVL‐positive MRSA.
A survey on subtypes and clinical characteristics of 1061 patients with urticaria in the primary care institutes in Japan
Authors: Saito Ryo , Takahagi Shunsuke , Nakano Fumi , Furutani Kiyoshi , Mihara Shoji , Numata Tsunemi , Kameyoshi Yoshikazu , Tanaka Toshihiko , Shindo Hajime , Niimi Naomasa , Iwamoto Kazumasa , Hiragun Takaaki , Hiragun Makiko , Tanaka Akio , Hide Michihiro
Published: August 2022

The prevalence of urticaria has been reported mostly in Europe and North America. However, precise information regarding its subtypes and clinical characteristics in primary care practice, especially in Asian countries, are scant. Patients with urticaria and/or angioedema who visited nine primary clinics of accredited dermatologists and allergologists in Japan were recruited from October to November 2020. The information of age, sex, disease duration, urticaria control test (UCT), and concomitant urticaria subtypes were collected. A total of 1061 patients participated. The number of patients was high in the 20 to 50 age groups with a peak in the 40s. The most frequent urticaria subtype was chronic spontaneous urticaria (CSU) followed by dermographism, acute spontaneous urticaria (ASU), angioedema, and cholinergic urticaria (CholU) (66.8%, 22.7%, 18.9%, 14.1% and 5.7% in all patients with urticaria). CSU development increased with age from the 20s to 50s, especially in females. Dermographism had a peak in the 40s. ASU had bimodal peaks in childhood and in the 30s. CholU was common in males in the 10–20s. Most angioedema patients were female with an increase in their 30s. Angioedema was solely present in 14 of 1061 participants (1.3%), while 136 (12.8%) had angioedema concomitant with urticaria. UCT showed poorly controlled urticaria with lower scores in patients with concomitant CSU and other subtypes than in those with CSU alone. Urticaria tends to develop in young to middle‐aged females. The most common urticaria subtype is CSU, while the number of patients with CholU is high and that of angioedema is low in Japan.
Low water availability enhances volatile‐mediated direct defences but disturbs indirect defences against herbivores
Authors: Lin Po‐An , Paudel Sulav , Bin Zainuddin Nursyafiqi , Tan Ching‐Wen , Helms Anjel , Ali Jared G. , Felton Gary W.
Published: August 2022

Interactions between plants and natural enemies of insect herbivores influence plant productivity and survival by reducing herbivory. Plants attract natural enemies via herbivore‐induced plant volatiles (HIPVs), but how water availability (WA) influences HIPV‐mediated defences is unclear.

We use tomato, Solanum lycopersicum, tomato fruitworm, Helicoverpa zea and two natural enemies, the parasitoid wasp, Microplitis croceipes and the predator spined soldier bug, Podisus maculiventris, to investigate the effect of WA on HIPV emission dynamics and associated plant defence.

We show that low WA initially increases total HIPV emission by tomato on the first day of herbivore exposure and, in contrast, reduces HIPV emission on the second day. Low WA enhances HIPVs that are mostly found in tomato trichomes. Notably, some volatiles inhibited by low WA are known attractants of natural enemies. Evidence from Y‐tube and in‐cage behavioural assays indicates that changes in HIPV emissions by low WA compromise the ability of tomato plants to attract natural enemies.

Synthesis. Based on our results, we propose a hypothesis where plants respond to low WA by enhancing repellent HIPV emissions and reducing the emission of HIPVs that attract natural enemies, which disrupts natural enemy‐mediated plant indirect defences, but enhances plant direct defence against herbivores.
Deep brain stimulation of the anterior nucleus of the thalamus for drug‐resistant epilepsy: Long‐term efficacy and outcomes from a prospective cohort
Authors: Cheung Eric Y. H. , Lau Claire K. Y. , Leung Howan H. W. , Fung Eva L. W. , Tang Venus Y. H. , Cheung Tom C. Y. , Kwong William K. M. , Zhu Xian Lun , Chan David Y. C. , Chan Danny T. M. , Poon Wai Sang
Published: August 2022

Aim

The anterior nucleus of the thalamus (ANT) has been one of the deep brain stimulation (DBS) targets for drug‐resistant epilepsy. This study aims to investigate the control of seizures among patients with ANT DBS for epilepsy. We have pioneered DBS for epilepsy in Hong Kong since 2015 and this study aims to report the long‐term outcomes from a prospective cohort.

Methods

This is a prospective cohort study of ANT DBS for adult patients with drug‐resistant epilepsy, who are unsuitable for resective epilepsy surgery.

Results

Six patients (3 females and 3 males, mean age 31.3) received bilateral ANT DBS in a tertiary university hospital from 2015 to 2018 (one in 2015, two in 2017 and three in 2018). Both frontal transventricular and parietal approaches were used. The active contacts were selected based on the closest Euclidean distance to the mammillothalamic tract and ANT junction. Five of the six cases (83.3%) achieved greater than 50% reduction in seizures after the operations. The median percentage of reduction in seizures was 58.5% at 3 years after DBS (range, 32.7%–80%). Overall, there was a trend of improving seizure control rate from year 1 to year 6 after the ANT DBS operations.

Conclusions

This is the first report of ANT DBS for drug‐resistant epilepsy in Hong Kong. The results are encouraging. ANT DBS for drug‐resistant epilepsy is effective and sustained in long term. The treatment option of ANT DBS should be considered in suitable candidates with drug‐resistant epilepsy in our locality.
Spatial and Temporal Variations in Phosphorus Loads in the Illinois River Basin, Illinois USA
Authors: McIsaac Gregory F. , Hodson Timothy O. , Markus Momcilo , Bhattarai Rabin , Kim Daniel Chulgi
Published: August 2022

Total phosphorus (TP) loads in many rivers in the north‐central United States have increased, including the Illinois River at Valley City, Illinois, USA, which increased 39% from the periods 1989–1996 to 2015–2019 despite efforts to reduce loads from point and nonpoint sources. Here, we quantify long‐term variations in phosphorus (P) loads in the Illinois River and its tributaries and identify factors that may be causing the variations. We calculated river loads of dissolved (DP) and particulate P (PP), total and volatile suspended solids (TSS and VSS), and other potentially related constituents at 41 locations. DP loads generally increased and PP and TSS loads generally decreased from 1989–1996 to 2015–2019. During 1989–1996, P accumulated in the lower basin between Marseilles and Valley City (excluding monitored tributaries). This portion of the basin is very flat and accumulates sediment. During 2015–2019, this section shifted from being a net sink to being a net source of P, accounting for 78% of the increased TP load at Valley City. We present evidence supporting several mechanisms that could have caused this shift: increased DP and chloride loads, reduced sulfate and nitrate concentrations influencing ionic strength and redox potential in the sediments, and increased VSS loads at Valley City possibly indicating greater algal production and contributing to hypoxia in lower river sediments. Additional research is needed to quantify the relative importance of these mechanisms.
Missed nursing care in the COVID‐19 pandemic in Iran
Authors: Hosseini Zeinab , Raisi Leila , Maghari Amir Hossein , Karimollahi Mansoureh
Published: August 2022

Background

Quality of care is one of the most critical issues in nursing care today. Moreover, all health care employees are responsible for providing support and high‐quality, safe care. However, nurses caring for COVID‐19 patients face problems such as unfamiliar work environments, exposure to the disease, lack of experience in their new positions, and close public and media attention. This study aimed to investigate missed nursing care and the reasons for missed nursing care during the coronavirus disease 2019 (COVID‐19) pandemic in Iran.

Methods

This cross‐sectional study included 135 nurses working in COVID‐19 units. Data were collected using the MISSCARE Survey. The significance level for the statistical tests was set at p < 0.05.

Results

Most of the participants were women and had a bachelor's degree in nursing. There was a lack of supportive and necessary care more than any other form of care. According to nurses, the most common reasons for missed care were urgent patient situations, inadequate staff, and an unexpected rise in patient volume and/or patient acuity on the unit.

Conclusion

Generally, the results showed that being positioned in a new situation and unfamiliarity with the disease had a significant impact—among nurses—on the amount of care provided. Managers can use this information to solve existing missed‐nursing‐care problems and contribute to improving the quality of care.

These results can be helpful in controlling missed nursing care and finding a more optimal solution for this problem; thus, we can improve the quality of care delivery and increase the satisfaction of nurses and patients. Additionally, an understanding of the kind of missing nursing care during a pandemic can positively enhance the management of similar situations in the future.
Italy: Political Developments and Data in 2021
Authors: RUSSO LUANA , SANDRI GIULIA , SEDDONE ANTONELLA
Published: August 2022

In Italy, 2021 has been a year marking a turning point in the struggle against the COVID‐19 pandemic, and a time of economic, political and social transition. The country has reaped several important successes, policy‐wise, both with regard to the efficacy of its vaccination campaign and to the drafting of its National Recovery and Resilience Plan (NRRP). All this was achieved after a quite troubled start of the year, with the fall of the Conte II government and the arrival in office of the new Prime Minister, Mario Draghi. The effects of the pandemic and the advent of the Draghi government affected both the dynamic of competition in the Italian party system and the intra‐party conflicts. The 2021 round of Italian local elections, involving thousands of municipalities, triggered a surprising victory for the centre left and marked an important shift in the electoral balance of power between Italian parties.
An ensemble learning integration of multiple CNN with improved vision transformer models for pest classification
Authors: Xia Wanshang , Han Dezhi , Li Dun , Wu Zhongdai , Han Bing , Wang Junxiang
Published: August 2022

Pests are the main threats to crop growth, and the precision classification of pests is conducive to formulating effective prevention and governance strategies. In response to the problems of low efficiency and inadaptability to the large‐scale environment of existing pest classification methods, this paper proposes a new pest classification method based on a convolutional neural network (CNN) and an improved Vision Transformer model. First, the MMAlNet is designed to extract the characteristics of the identification object from different scales and finer granularity. Then, a classification model called DenseNet Vision Transformer (DNVT) combining a CNN and an improved vision transformer model is proposed. The proposed DNVT captures both long distance dependencies and local characteristic modelling capabilities, which can effectively improve pest classification accuracy. Finally, the ensemble learning algorithm is used to learn MMAlNet and DNVT classification forecasts for soft voting, further enhancing the classification accuracy of pests. The simulation experiment results on the D0 and IP102 datasets show that the proposed method attained a maximum classification of 99.89 and 74.20%, respectively, which is better than other state‐of‐the‐art methods and has a high practical application value.
Evaluation of Thromboelastography 6s prognostication of fibrinogen supplementation in pediatric cardiac surgery
Authors: Lindhardt Rasmus Bo , Kronborg Jonas Rønne , Wanscher Michael , Andersen Lars Willy , Gjedsted Jakob , Ravn Hanne Berg
Published: August 2022

Background

Implementation of point‐of‐care tests is recommended to provide tailored substitution during cardiac surgery. The measurement and substitution of fibrinogen have gained particular interest since it is the first coagulation factor to become depleted during cardiac surgery. However, the prognostic ability of thromboelastography (TEG) 6s has not been evaluated in pediatric patients.

The aim of the present study was to describe patient characteristics of infants receiving fibrinogen substitution during cardiac surgery and evaluate the prognostic ability of TEG6s after weaning off cardiopulmonary bypass (CPB).

Methods

Infants undergoing congenital cardiac surgery with CPB were retrospectively included (n = 279) between January 2017 to July 2019. Patient and perioperative data were collected on the day of surgery until 6:00 AM the next morning. Hemostatic capacity was assessed with TEG6s.

The efficacy of TEG‐functional fibrinogen‐maximal amplitude (TEG‐FF‐MA) measurements for the prediction of intraoperative bleeding, and thereby cryoprecipitate need, was evaluated by a sensitivity and specificity analysis.

Results

Among 174 children with TEG‐FF‐MA data, 147 (84%) received cryoprecipitate intraoperatively. Cryoprecipitate administration was associated with younger age 66 (10–132) versus 98 (45–204) days (p = .044), higher RACHS‐1 classification, and intraoperative bleeding 21 (11–47) versus 5 (3–13) ml/kg (p < .001, mean difference 29 ml/kg [CI: 8–50]). Median TEG‐FF‐MA values were lower in transfused children 7.6 (5.3–11.0) versus 10.5 (7.3–13.4) mm (p = .004, mean difference − 2.4 mm [CI: −4.1 to − 0.73]).

The volume of cryoprecipitate was associated with bypass time, TEG‐FF‐MA values, and in particular intraoperative bleeding volumes.

A TEG‐FF‐MA threshold of 10.0 mm, resulted in sensitivity: 74%, specificity: 56%, positive predictive value: 80%, and a negative predictive value of 47% for the prediction of intraoperative bleeding (>10 ml/kg) and consequently a need of cryoprecipitate transfusion.

Conclusion

Fibrinogen substitution in infants was associated with younger age and higher RACHS‐1 category.

The prognostic value of TEG6s was evaluated, and cryoprecipitate transfusion was related to TEG‐FF‐MA values, but also CPB‐time, surgical complexity, and in particular excessive intraoperative bleeding. A clear‐cut threshold for TEG‐FF‐MA is difficult to establish in infants undertaken congenital heart surgery.
Markers of neutrophil mediated inflammation associate with disturbed continuous electroencephalogram after out of hospital cardiac arrest
Authors: Pekkarinen Pirkka T. , Carbone Federico , Minetti Silvia , Ramoni Davide , Ristagno Giuseppe , Latini Roberto , Wihersaari Lauri , Blennow Kaj , Zetterberg Henrik , Toppila Jussi , Jakkula Pekka , Reinikainen Matti , Montecucco Fabrizio , Skrifvars Markus B.
Published: August 2022

Background

Achieving an acceptable neurological outcome in cardiac arrest survivors remains challenging. Ischemia‐reperfusion injury induces inflammation, which may cause secondary neurological damage. We studied the association of ICU admission levels of inflammatory biomarkers with disturbed 48‐hour continuous electroencephalogram (cEEG), and the association of the daily levels of these markers up to 72 h with poor 6‐month neurological outcome.

Methods

This is an observational, post hoc sub‐study of the COMACARE trial. We measured serum concentrations of procalcitonin (PCT), high‐sensitivity C‐reactive protein (hsCRP), osteopontin (OPN), myeloperoxidase (MPO), resistin, and proprotein convertase subtilisin/kexin type 9 (PCSK9) in 112 unconscious, mechanically ventilated ICU‐treated adult OHCA survivors with initial shockable rhythm. We used grading of 48‐hour cEEG monitoring as a measure for the severity of the early neurological disturbance. We defined 6‐month cerebral performance category (CPC) 1–2 as good and CPC 3–5 as poor long‐term neurological outcome. We compared the prognostic value of biomarkers for 6‐month neurological outcome to neurofilament light (NFL) measured at 48 h.

Results

Higher OPN (p = .03), MPO (p < .01), and resistin (p = .01) concentrations at ICU admission were associated with poor grade 48‐hour cEEG. Higher levels of ICU admission OPN (OR 3.18; 95% CI 1.25–8.11 per ln[ng/ml]) and MPO (OR 2.34; 95% CI 1.30–4.21) were independently associated with poor 48‐hour cEEG in a multivariable logistic regression model. Poor 6‐month neurological outcome was more common in the poor cEEG group (63% vs. 19% p < .001, respectively). We found a significant fixed effect of poor 6‐month neurological outcome on concentrations of PCT (F = 7.7, p < .01), hsCRP (F = 4.0, p < .05), and OPN (F = 5.6, p < .05) measured daily from ICU admission to 72 h. However, the biomarkers did not have independent predictive value for poor 6‐month outcome in a multivariable logistic regression model with 48‐hour NFL.

Conclusion

Elevated ICU admission levels of OPN and MPO predicted disturbances in cEEG during the subsequent 48 h after cardiac arrest. Thus, they may provide early information about the risk of secondary neurological damage. However, the studied inflammatory markers had little value for long‐term prognostication compared to 48‐hour NFL.
Attention bias and alcohol craving: Differential effects via biological sex and mood
Authors: Moskal Katie R. , Dvorak Robert D. , Burr Emily K. , El Helou Gaelle , Cora Jessica L. , De Leon Ardhys N. , Leary Angelina V.
Published: August 2022

Background

Attentional bias (AB) has been linked to alcohol use, mood, and alcohol craving, with key differences across different types of mood and biological sex. However, further exploration of the role of AB across these alcohol variables is needed. The current study examined the relationship between mood and AB as predictors of alcohol craving using ecological momentary assessment (EMA). Exploratory analysis examined these effects as a function of biological sex.

Methods

Participants (n = 69) from a Midwestern University carried a mobile device for 15 days and provided ratings of momentary mood (positive mood, anxious mood, and sad mood), alcohol craving, and AB. Data were analyzed using a two‐level multilevel regression model, with associations between craving, mood, and AB examined at both the momentary and between‐subjects levels.

Results

Across assessments, positive and negative moods were positively associated with momentary craving, with AB found to operate differently between men and women. At the within‐subjects level, increases in positive mood among men strengthened the AB‐craving association, while women showed stronger AB‐craving associations when positive mood decreased. At the between‐subjects level, trait‐like sadness led to positive AB‐craving associations for men, however, this was the opposite for women. Similarly, AB‐craving associations were positive and robust for men with trait‐like positive mood but again the opposite was observed for women.

Conclusions

The findings highlight the importance and nuances of biological sex in the context of mood, AB, and craving. Interventions targeting AB and/or emotion regulation may yield different outcomes for men and women.
The threat of an indigenous medicinal plant encroacher: Artemisia afra in Klipriviersberg Nature Reserve, Johannesburg, South Africa
Authors: Setshedi Kgalalelo T. A. , Newete Solomon W. , Witkowski Ed T. F.
Published: August 2022

Artemisia afra was identified as an encroaching shrub in the Klipriviersberg Nature Reserve (KNR). Ecological factors that influence the encroachment of A. afra and its population structure were unknown, making it difficult to monitor and control the spread of the plant. This study assessed the density and size‐class distributions (SCD) of A. afra across the main habitats in the KNR (streamside, plains and ridges, with ridges divided into crest, mid‐slope and bottom slope), as well as the relationship between A. afra density and certain ecological factors. Results showed that there was a significant difference (p < 0.05) between plant density on the different habitats with the ridge and bottom slope having by far the highest density (>900 plants/ha). Canopy volume was considered the best measure for the SCD of A. afra. Overall, the population structure of A. afra displayed an inverse J‐shaped curve, indicating that despite clearing efforts and the drought of 2015–2016, it is effectively a recruiting population. Over 71% of the A. afra population were flowering, suggesting relatively rapid attainment of reproductive maturity, and high seed production. Hence, the high levels of encroachment are likely to continue. Further research on controlling A. afra with the integrated use of more intense winter fires, herbicides and the feasibility of sustainable harvesting of this medicinal plant should be undertaken. We also need a much better understanding of the regeneration ecology of A. afra in order to better control it.
Efficacy of intravenous immunoglobulin in the treatment of recurrent spontaneous abortion: A systematic review and meta‐analysis
Authors: Shi Yimin , Tan Dongmei , Hao Baozhen , Zhang Xiurong , Geng Wei , Wang Yayu , Sun Jianyi , Zhao Yue
Published: August 2022

Objective

We aimed to evaluate the efficacy of IVIG in the treatment with patients with recurrent spontaneous abortion (RSA).

Methods

PubMed, Embase, Web of science, Cochrane library were searched for randomized controlled (RCTs) about effect of IVIG on RSA from inception to August 20, 2021. Values of standardized mean differences (SMD) were determined for continuous outcomes.

Results

A total of 15 articles involving 902 patients were included in meta‐analysis. Compared with the control group, IVIG can increase the live birth rate of recurrent spontaneous abortion patients [OR = 3.06, 95%CI (1.23, 7.64, P = .02]. However, recurrent abortion was divided into primary and secondary abortion for subgroup analysis, and there was no statistical difference. Besides, IVIG can also increase the expression in peripheral blood CD3+[OR = .4, 95%CI(‐2.47, 3.15, P = .81],CD4+[OR = 1.16, 95%CI(‐4.60, 6.93, P = .69], and a decrease in the expression of CD8+[OR = ‐1.78, 95%CI(‐5.30, 1.75, P = .32], but there is no statistical significance.

Conclusions

IVIG can significantly increase the live birth rate of recurrent spontaneous abortion. However, the evidence needs further verification and the curative effect is uncertain. It is necessary to further explore the pathogenesis of recurrent abortion and the mechanism of IVIG in the treatment of recurrent spontaneous abortion. Besides, more high‐quality randomized controlled trials suitable for population, race, dosage and timing of IVIG in the treatment of recurrent abortion are needed to confirm its effectiveness, and effective systematic evaluation is also needed to evaluate its use benefit.
Coculture of adipose‐derived mesenchymal stem cells/macrophages on decellularized placental sponge promotes differentiation into the osteogenic lineage
Authors: Khosrowpour Zahra , Hashemi Seyed Mahmoud , Mohammadi‐Yeganeh Samira , Moghtadaei Mehdi , Brouki Milan Peiman , Moroni Lorenzo , Kundu Subhas C. , Gholipourmalekabadi Mazaher
Published: August 2022

Background

Several factors like three‐dimensional microstructure, growth factors, cytokines, cell–cell communication, and coculture with functional cells can affect the stem cells behavior and differentiation. The purpose of this study was to investigate the potential of decellularized placental sponge as adipose‐derived mesenchymal stem cells (AD‐MSCs) and macrophage coculture systems, and guiding the osteogenic differentiation of stem cells.

Methods

The decellularized placental sponge (DPS) was fabricated, and its mechanical characteristics were evaluated using degradation assay, swelling rate, and pore size determination. Its structure was also investigated using hematoxylin and eosin staining and scanning electron microscopy. Mouse peritoneal macrophages and AD‐MSCs were isolated and characterized. The differentiation potential of AD‐MSCs co‐cultured with macrophages was evaluated by RT‐qPCR of osteogenic genes on the surface of DPS. The in vivo biocompatibility of DPS was determined by subcutaneous implantation of scaffold and histological evaluations of the implanted site.

Results

The DPS had 67% porosity with an average pore size of 238 μm. The in vitro degradation assay showed around 25% weight loss during 30 days in PBS. The swelling rate was around 50% during 72 h. The coculture of AD‐MSCs/macrophages on the DPS showed a significant upregulation of four differentiation osteogenic lineage genes in AD‐MSCs on days 14 and 21 and a significantly higher mineralization rate than the groups without DPS. Subcutaneous implantation of DPS showed in vivo biocompatibility of scaffold during 28 days follow‐up.

Conclusions

Our findings suggest the decellularized placental sponge as an excellent bone substitute providing a naturally derived matrix substrate with biostructure close to the natural bone that guided differentiation of stem cells toward bone cells and a promising coculture substrate for crosstalk of macrophage and mesenchymal stem cells in vitro.
Nitrous oxide in labour predicted newborn screening total homocysteine and is a potential risk factor for infant vitamin B12 deficiency
Authors: Ljungblad Ulf Wike , Lindberg Morten , Eklund Erik A. , Saeves Ingjerd , Bjørke‐Monsen Anne‐Lise , Tangeraas Trine
Published: August 2022

Aim

Risk factors for vitamin B12 deficiency in infants are not fully understood. The aim of the study was to assess predictors of total homocysteine and methylmalonic acid analysed in newborn screening dried blood spots.

Methods

In a Norwegian case control study, we analysed total homocysteine and methylmalonic acid in newborn screening dried blood spots of 86 infants clinically diagnosed with vitamin B12 deficiency during 2012–2018. Results were compared to 252 healthy infants and 400 dried blood spot controls. Medical records were reviewed, and mothers completed questionnaires.

Results

Both total homocysteine and methylmalonic acid were significantly higher on newborn screening dried blood spots in infants later clinically diagnosed with vitamin B12 deficiency than controls. Multiple regression analysis showed that the dose of nitrous oxide during labour was the strongest predictor for total homocysteine level in newborn screening dried blood spots for all infants, with larger effect in infants later clinically diagnosed with vitamin B12 deficiency than controls.

Conclusion

Nitrous oxide dose during labour was a predictor for total homocysteine and may impact the interpretation of total homocysteine analysis in newborn screening. Nitrous oxide is suggested as a contributing risk factor for infants prone to develop vitamin B12 deficiency.
Peripheral neuropathies after BRAF and/or MEK inhibitor treatment: A pharmacovigilance study
Authors: Picca Alberto , Birzu Cristina , Berzero Giulia , Sanchez‐Pena Paola , Gaboriau Louise , Vidil Faustine , Lenglet Timothée , Tafani Camille , Ricard Damien , Psimaras Dimitri , Bihan Kévin
Published: August 2022

Reports suggested the potential occurrence of peripheral neuropathies (PN) in patients treated with BRAF (BRAFi) and/or MEK inhibitors (MEKi) for BRAF‐activated tumours. We aimed to better characterize these PN. We queried the French pharmacovigilance database for all cases of PN attributed to BRAFi and/or MEKi. Fifteen patients were identified. Two main clinical PN phenotypes were seen. Six patients presented a length‐dependent, axonal polyneuropathy: symptoms were mostly sensory and affecting the lower limbs; management and outcome were variable. Nine patients developed a demyelinating polyradiculoneuropathy: symptoms affected the four limbs and included hypoesthesia, weakness and ataxia; cranial nerves were involved in four cases; most patients received intravenous immunoglobulins or glucocorticoids, with variable outcome; one patient was rechallenged with a different BRAFi/MEKi combination with a rapid relapse in symptoms. In conclusion, patients under BRAFi/MEKi therapy may develop treatment‐induced PN. Two main phenotypes can occur: a symmetric, axonal, length‐dependent polyneuropathy and a demyelinating polyradiculoneuropathy.
The role of high‐conductance calcium‐activated potassium channel in headache and migraine pathophysiology
Authors: Al‐Karagholi Mohammad Al‐Mahdi , Hakbilen Cemile Ceren , Ashina Messoud
Published: August 2022

Migraine is a common, neurovascular headache disorder with a complex molecular interplay. The involvement of ion channels in the pathogenesis of migraine gathered considerable attention with the findings that different ion channels subfamilies are expressed in trigeminovascular system, the physiological substrate of migraine pain, and several ion channel openers investigated in clinical trials with diverse primary endpoints caused headache as a frequent side effect. High‐conductance (big) calcium‐activated potassium (BKCa) channel is expressed in the cranial arteries and the trigeminal pain pathway. Recent clinical research revealed that infusion of BKCa channel opener MaxiPost caused vasodilation, headache and migraine attack. Thus, BKCa channel is involved in pathophysiological mechanisms underlying headache and migraine, and targeting BKCa channel presents a new potential strategy for migraine treatment.
The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP‐1α/miR‐143 signalling
Authors: Bagalagel Alaa , Diri Reem , Noor Ahmad , Almasri Deina , Bakhsh Hussain T. , Kutbi Hussam I. , Al‐Gayyar Mohammed M. H.
Published: August 2022

Patients with ulcerative colitis (UC) experience diarrhoea, hematochezia and abdominal pain. UC is a well‐known health challenge affecting 200–250 per 100 000 individuals worldwide, with a similar prevalence in both sexes and elevated upon activation of gut immune responses. We evaluated the potential therapeutic effects of cycloastragenol in experimentally induced UC rats and examined the modulation of sphingosine kinase (SphK), macrophage inflammatory protein (MIP)‐1α and miR‐143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP‐1α, B‐cell lymphoma 2 (BCL2), BCL2‐associated X (BAX), miR‐143, NF‐κB, tumour necrosis factor (TNF)‐α and active caspase‐3. Colon sections were examined using electron microscopy; additional sections were stained with haematoxylin–eosin or immunostained with anti‐TNF‐α and anti‐caspase‐3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a nondistinct brush border with atypical microvilli. Haematoxylin–eosin staining showed damaged intestinal glands, severe haemorrhage and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP‐1α, BAX, NF‐κB, TNF‐α and active caspase‐3, associated with BCL2 and miR‐143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP‐1α/miR‐143, subsequently deactivating inflammatory and apoptotic pathways.
Rare germline ATM variants of uncertain significance in chronic lymphocytic leukaemia and other cancers
Authors: Petrackova Anna , Savara Jakub , Turcsanyi Peter , Gajdos Petr , Papajik Tomas , Kriegova Eva
Published: August 2022

Germline pathogenic ATM (ataxia‐telangiectasia mutated) variants are associated with the risk of multiple cancers; however, genetic testing reveals a large number of ATM variants of uncertain significance (VUS). Here, we studied germline ATM variants occurring in a real‐world cohort of 336 patients with chronic lymphocytic leukaemia (CLL) and public cancer whole‐exome/genome‐sequencing datasets (445 CLL, 75 mantle cell lymphoma, 216 metastatic breast cancer, 140 lung cancer patients). We found that two‐thirds of rare germline ATM variants are pathogenic (18%–50%) or VUS‐predicted pathogenic (50%–82%), depending on cancer type and reaching a prevalence of up to 8%, and one‐third are VUS‐predicted benign. Patients with both pathogenic and VUS‐predicted pathogenic variants, all heterozygous, mostly missense, are more predisposed to biallelic ATM inactivation by acquiring deletion (del)11q than patients without these variants, similar to patients with somatic ATM variants. A functional assay of ATM activity in primary CLL cells proved that VUS‐predicted pathogenic ATM variants partially reduce ATM activity and concurrent del(11q) leads to complete loss of ATM activity. The rare germline variants were associated with reduced progression‐free survival in CLL on novel agents, comparable to somatic ATM or TP53 disruptions. Our results highlight the need to determine the pathogenicity of VUS in clinically relevant genes such as ATM.
Donepezil inhibits neuromuscular junctional acetylcholinesterase and enhances synaptic transmission and function in isolated skeletal muscle
Authors: Redman Robert R. , Mackenzie Harry , Dissanayake Kosala N. , Eddleston Michael , Ribchester Richard R.
Published: August 2022

Background and Purpose

Donepezil, a piperidine inhibitor of acetylcholinesterase (AChE) prescribed for treatment of Alzheimer's disease, has adverse neuromuscular effects in humans, including requirement for higher concentrations of non‐depolarising neuromuscular blockers during surgery. Here, we examined the effects of donepezil on synaptic transmission at neuromuscular junctions (NMJs) in isolated nerve‐muscle preparations from mice.

Experimental Approach

We measured effects of therapeutic concentrations of donepezil (10 nM to 1 μM) on AChE enzymic activity, muscle force responses to repetitive stimulation, and spontaneous and evoked endplate potentials (EPPs) recorded intracellularly from flexor digitorum brevis muscles from CD01 or C57BlWldS mice.

Key Results

Donepezil inhibited muscle AChE with an approximate IC50 of 30 nM. Tetanic stimulation in sub‐micromolar concentrations of donepezil prolonged post‐tetanic muscle contractions. Preliminary Fluo4‐imaging indicated an association of these contractions with an increase and slow decay of intracellular Ca2+ transients at motor endplates. Donepezil prolonged spontaneous miniature EPP (MEPP) decay time constants by about 65% and extended evoked EPP duration almost threefold. The mean frequency of spontaneous MEPPs was unaffected but the incidence of ‘giant’ MEPPs (gMEPPs), some exceeding 10 mV in amplitude, was increased. Neither mean MEPP amplitude (excluding gMEPPs), mean EPP amplitude, quantal content or synaptic depression during repetitive stimulation were significantly altered by concentrations of donepezil up to 1 μM.

Conclusion and Implications

Adverse neuromuscular signs associated with donepezil therapy, including relative insensitivity to neuromuscular blockers, are probably due to inhibition of AChE at NMJs, prolonging the action of ACh on postsynaptic nicotinic acetylcholine receptors but without substantively impairing evoked ACh release.
Dysferlinopathies: Clinical and genetic variability
Authors: Ivanova Alisa , Smirnikhina Svetlana , Lavrov Alexander
Published: August 2022

Dysferlinopathies are a clinically heterogeneous group of diseases caused by mutations in the DYSF gene encoding the dysferlin protein. Dysferlin is mostly expressed in muscle tissues and is localized in the sarcolemma, where it performs its main function of resealing and maintaining of the integrity of the cell membrane. At least four forms of dysferlinopathies have been described: Miyoshi myopathy, limb‐girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset, and isolated hyperCKemia. Here we review the clinical features of different forms of dysferlinopathies and attempt to identify genotype–phenotype correlations. Because of the great clinical variability and rarety of the disease and mutations little is known, how different phenotypes develop as a result of different mutations. However, missense mutations seem to induce more severe disease than LoF, which is typical for many muscle dystrophies. The role of several specific mutations and possible gene modifiers is also discussed in the paper.
Diamond‐Blackfan anaemia caused by a de novo initiation codon mutation resulting in a shorter isoform of GATA1
Authors: Chen Tongtong , Zhang Qianqian , Shang Xuan , Zou Shaomin , Qin Jiaofeng , Li Kui , Lin Bin , Tao Zhenzhong , Long Xingjiang , Xu Xiangmin
Published: August 2022

Diamond‐Blackfan anaemia (DBA) is an inherited marrow failure disorder characterised by selective erythroid aplasia. Herein, we reported a case of DBA caused by a novel GATA1 gene mutation. The proband manifested normocytic normochromic anaemia, while the parents were asymptomatic. Next‐generation sequencing identified a novel de novo mutation at GATA1 initiation codon (GATA1:c.3G>A) in the proband. The mutation led to a shortened GATA1 protein (GATA1s), which caused a reduction in full‐length functional GATA1 protein (GATA1fl). This is the first report of GATA1‐related DBA patient in the East Asian population, which expanded the mutational spectrum of DBA furthering understanding of its pathogenesis.
The analgesic and anti‐haemorrhagic efficacy of platelet‐rich plasma in tonsillectomy: A systematic review and meta‐analysis of randomised controlled trials
Authors: Albazee Ebraheem , Diab Sherein , Awad Ahmed K. , Aboeldahab Heba , Abdella Walid Shaban , Abu‐Zaid Ahmed
Published: August 2022

Objectives

To evaluate the analgesic and anti‐haemorrhagic efficacy of platelet‐rich plasma (PRP) among patients undergoing tonsillectomy.

Design

A systematic review and meta‐analysis of randomised controlled trials (RCTs).

Setting

PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases were screened from inception until July 2021, and updated in December 2021.

Participants

Patients undergoing tonsillectomy.

Main outcome measures

The efficacy endpoints of postoperative pain and haemorrhage were summarised as standardised mean difference (SMD) and risk ratio (RR), respectively, with 95% confidence interval (CI).

Results

Seven RCTs Seven RCTs were analysed, comprising a total of 392 patients. Risk of bias evaluation showed an overall high risk in one RCT, low risk in four RCTs and some concerns in two RCTs. The pooled results revealed that the mean postoperative pain score was significantly reduced in favour of the PRP group compared with the control group (SMD = −1.38, 95% CI [−1.91, −0.85], p < 0.001). Subgroup analysis showed the effect estimate was statistically significant for early postoperative pain (Day 0 to Day 3), without substantial difference between both groups on late postoperative pain (Days 5 and 7). Moreover, the rate of postoperative haemorrhage was significantly reduced in favour of the PRP group compared with the control group (RR = 0.16, 95% CI [0.05, 0.50], p = 0.001). Subgroup analysis showed the effect estimate was statistically significant for the rate of primary and secondary haemorrhage.

Conclusion

PRP was associated with significant reduction in postoperative pain and haemorrhage among patients undergoing tonsillectomy.
Incidence of skin diseases in healthcare workers before and during the COVID‐19 pandemic at Trieste hospitals (northeastern Italy)
Authors: Piapan Linda , Bramuzzo Davide , Rui Francesca , Filon Francesca Larese
Published: August 2022

Background

Occupational skin diseases (OSDs) are common in healthcare workers (HCWs).

Objectives

To investigate and compare the incidence and clinical features of OSDs among HCWs before and during the COVID‐19 pandemic.

Materials and Methods

Incident cases of OSDs were investigated in the cohort of HCWs at Trieste Hospitals from 1 July 2018 (3340 workers) to 31 October 2021 (137 532 person‐months).

Results

The monthly incidence was ranging from 0 to 11.90 cases per 10 000 person‐months in pre‐COVID‐19 period (cumulative incidence 4.22; 95% confidence interval [CI]: 2.9–6.0) and from 0 to 13.61 cases per 10 000 person‐months in COVID‐19 period (cumulative incidence 5.06; 95% CI: 3.6–6.9). The incidence rate ratio (IRR) between COVID‐19 and pre‐COVID‐19 period was 1.22 (95% CI: 0.73–1.98). The incidence of OSDs in the COVID‐19 period was 6.1 (4.2–8.6) and 2.7 (95% CI: 1.1–5.6) cases × 10 000 person‐months for women and men, respectively, with an IRR of 2.25 (95% CI: 0.98–5.9). Incidence in nurses in the COVID‐19 period was 6.7 (95% CI: 4.2–10.2) cases × 10 000 person‐months.

Conclusions

Incidence of OSDs was a little bit higher during the COVID‐19 pandemic compared to the previous period but fluctuation of numbers were mainly related to calendar period, with higher incidence in winter and spring. Incidence data were higher than that observed in 2004–2013 in the same cohort. Face dermatitis cases doubled after the start of COVID‐19 pandemic. Overall data demonstrated a non‐significant increase of OSDs in HCWs during the pandemic, probably due to the preventive strategies set up in our cohort over the years.
Exosome‐shuttled mitochondrial transcription factor A mRNA promotes the osteogenesis of dental pulp stem cells through mitochondrial oxidative phosphorylation activation
Authors: Guo Jia , Zhou Feng , Liu Zhi , Cao Yuan , Zhao Wanming , Zhang Zheru , Zhai Qiming , Jin Yan , Li Bei , Jin Fang
Published: August 2022

Objectives

The treatment of bone defects by stem cells (MSCs) has achieved limited success over the recent few decades. The emergence of exosomes provides a new strategy for bone regeneration. Here, we aimed to investigate the effect and mechanisms of exosomes combined with dental pulp stem cells (DPSCs) on bone regeneration.

Materials and Methods

We isolated exosomes from stem cells from human exfoliated deciduous teeth (SHED) aggregates and evaluated the efficacy of exosomes combined with DPSCs in a cranial bone defect model. The potential mechanisms were further investigated.

Results

The effect of exosomes combined with DPSCs was remarkable on bone regeneration in vivo and exosomes promoted osteogenic differentiation of DPSCs in vitro. Mechanistically, exosomes increased the expression of mitochondrial transcription factor A (TFAM) in DPSCs by transferring TFAM mRNA. Moreover, highly expressed TFAM in DPSCs enhanced glutamate metabolism and oxidative phosphorylation (OXPHOS) activity.

Conclusions

Consequently, exosomes strengthened bone regeneration of DPSCs through the activation of mitochondrial aerobic metabolism. Our study provides a new potential strategy to improve DPSC‐based bone regenerative treatment.
Genetic evidence to inform management of rare genetic variants and gene flow: Balancing the conservation of the rare “Spirit bear” allele and population genetic diversity across a complex landscape
Authors: Henson Lauren H. , Service Christina , Stronen Astrid Vik , Moody Jason , Housty William , Reece Donald , vonHoldt Bridgett , Darimont Chris T.
Published: August 2022

Incorporating genetic considerations into wildlife management can require balancing the conservation of rare genetic variants with the maintenance of gene flow. One system illustrating such trade‐offs is coastal British Columbia, Canada, where black bears (Ursus americanus) can carry a genetic variant responsible for white‐coated “Spirit bears.” We examined population genetic structure, diversity, and gene flow using 22 microsatellite loci for 357 individuals collected over a 23,500 km2 area from a long‐term noninvasive bear monitoring collaboration among the Gitga'at, Kitasoo/Xai'xais, Nuxalk, Haíɫzaqv, and Wuikinuxv First Nations and partnering scientists. We found broad‐ (two groups) and fine‐scale (eight groups) population structures. At the finer scale, three islands formed unique genetic groups and four genetic groups showed heterozygote deficiency, including two populations containing Spirit bear alleles. We additionally created effective estimation of migration surfaces and found that breaks among genetic groups and areas of lower than average migration aligned with wide waterways (>2 km). Given the apparent isolation of island groups, heterozygote deficiencies, and the distribution of the rare Spirit bear allele, we provide recommendations to prevent the loss of Spirit bear allele carriers and individuals contributing genetic diversity to isolated, genetically depauperate groups. More broadly, we highlight the value of locally led, fine‐scale genetic monitoring for wildlife management.