bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of immunogenicity of gene-deleted and subunit vaccines constructed against the emerging pseudorabies virus variants
Authors: Zhang Hong-liang , Zhang Rui-hua , Liu Gang , Li Gui-mei , Wang Feng-xue , Wen Yong-jun , Shan Hu
Published: May 2023

Background

Pseudorabies (PR) (also called Aujeszky’s disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections.

Methods

The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines.

Results

Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90–100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits.

Conclusions

The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.
Molecular triage of cervical screening samples in women 55–59 years of age: a pilot study
Authors: Helenius Gisela , Lillsunde-Larsson Gabriella , Bergengren Lovisa
Published: May 2023

Background

With HPV screening the specificity of screening positives has decreased, even with a cytological triage test. Increases in colposcopies and detection of benign or low-grade dysplasia are reported, not least in older women. These results highlight the necessity to find other triage tests in HPV screening strategies, so that women can be more accurately selected for colposcopy, thus minimizing the clinically irrelevant findings.

Methods

The study included 55- to 59-year-old women who exited the screening with normal cytology, but later in a follow-up test were positive for the HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 and had a cervical cone biopsy done. To model a screening situation with hrHPV-positive women, three different triage strategies, namely, cytology, genotyping and methylation, were performed. The study considered the effect of direct referral to colposcopy for HPV genotypes 16, 18, 31, 33, 45, 52 and 58, and methylation for FAM19A4 and hsa-mir124-2 and/or any form of abnormal cytology.

Results

Seven out of 49 women aged 55–59 years with hrHPV had a cone biopsy with high-grade squamous intraepithelial lesion. No triage method found all cases, and when comparing positive and negative predictive value and false negative rate, cytology showed better results than genotyping and methylation.

Conclusion

This study does not support a switch in triage strategies from cytology to hrHPV genotyping and methylation for women above 55 years of age yet, but demonstrates the need for more evidence on molecular triage strategies.
Sex-specific associations of matrix metalloproteinases in Alzheimer’s disease
Authors: Aksnes Mari , Edwin Trine H. , Saltvedt Ingvild , Eldholm Rannveig S. , Chaudhry Farrukh A. , Halaas Nathalie B. , Myrstad Marius , Watne Leiv O. , Knapskog Anne-Brita
Published: May 2023

Introduction

Alzheimer’s disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD.

Methods

In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aβ and tau pathology as well as disease progression. Further, we studied sex-specific interactions.

Results

MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aβ biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women.

Conclusion

Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.
Identification and validation of CCL2 as a potential biomarker relevant to mast cell infiltration in the testicular immune microenvironment of spermatogenic dysfunction
Authors: Dong Fan , Ping Ping , Wang Si-Qi , Ma Yi , Chen Xiang-Feng
Published: May 2023

Background

Spermatogenic dysfunction is an important cause of azoospermia. Numerous studies have focused on germ-cell-related genes that lead to spermatogenic impairment. However, based on the immune-privileged characteristics of the testis, the relationship of immune genes, immune cells or immune microenvironment with spermatogenic dysfunction has rarely been reported.

Results

Using integrated methods including single-cell RNA-seq, microarray data, clinical data analyses and histological/pathological staining, we found that testicular mast cell infiltration levels were significantly negatively related to spermatogenic function. We next identified a functional testicular immune biomarker, CCL2, and externally validated that testicular CCL2 was significantly upregulated in spermatogenic dysfunctional testes and was negatively correlated with Johnsen scores (JS) and testicular volumes. We also demonstrated that CCL2 levels showed a significant positive correlation with testicular mast cell infiltration levels. Moreover, we showed myoid cells and Leydig cells were two of the important sources of testicular CCL2 in spermatogenic dysfunction. Mechanistically, we drew a potential “myoid/Leydig cells-CCL2-ACKR1-endothelial cells-SELE-CD44-mast cells” network of somatic cell–cell communications in the testicular microenvironment, which might play roles in spermatogenic dysfunction.

Conclusions

The present study revealed CCL2-relevant changes in the testicular immune microenvironment in spermatogenic dysfunction, providing new evidence for the role of immunological factors in azoospermia.
ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer
Authors: Xin Shiyong , Liu Xiang , Li Ziyao , Sun Xianchao , Wang Rong , Zhang Zhenhua , Feng Xinwei , Jin Liang , Li Weiyi , Tang Chaozhi , Mei Wangli , Cao Qiong , Wang Haojie , Zhang Jianguo , Feng Lijin , Ye Lin
Published: May 2023

Background

Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq.

Methods

A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed.

Results

The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence.

Conclusions

The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.
Risk factors for school-based presenteeism in children: a systematic review
Authors: Woodland Lisa , Brooks Samantha K. , Webster Rebecca K. , Amlôt Richard , Rubin G. James
Published: May 2023

Introduction

Children attending school whilst unwell, known as school-based presenteeism, results in negative impacts on education and mental and physical health. We aimed to identify the risk factors for this behaviour.

Method

We conducted a systematic search of five databases (11 July 2022) using words associated with school (e.g., school and childcare) and presenteeism (e.g., presenteeism and sick leave). The studies are synthesised according to the risk factors associated with school-based presenteeism and are grouped into themes by related topics.

Results

Our review included 18 studies, with quantitative, qualitative, and mixed-method study designs. Children, parents, and school staff reported past incidents and intentions for future presenteeism. We identified five themes from these reports: perceptions about the illness / signs and symptom(s); children’s characteristics; children’s and parents’ motivations and attitudes towards school; organisational factors; and school sickness policy. Increased risk of school-based presenteeism was commonly linked to symptoms that were perceived low in severity and unidentifiable, children with a high school absence record, disbelief in children’s illness, unsupportive employers, vague school policies and financial consequences.

Conclusions

School-based presenteeism is complex due to the competing interests of the multiple individuals involved, such as children, parents, and school staff. Sickness policies need to include clear and specific guidance about illness and the signs and symptoms of diseases and should be communicated to all relevant individuals to mitigate against discrepancies in how the policy is interpreted. Furthermore, parents and school staff need support, such as financial and childcare, to be able to manage children when they are unwell.
A pilot screening for cognitive impairment through voice technology (WAY2AGE)
Authors: Moret-Tatay Carmen , Iborra-Marmolejo Isabel , Jorques-Infante María José , Bernabé-Valero Gloria , Beneyto-Arrojo María José , Irigaray Tatiana Quarti
Published: May 2023

Voice technology has grown exponentially, offering an opportunity to different fields, such as the health area. Considering that language can be a sign of cognitive impairment and most screening tools are based on speech measures, these devices are of interest. The aim of this work was to examine a screening tool for Mild Cognitive Impairment (MCI) through voice technology. For this reason, the WAY2AGE voice Bot was tested across Mini-Mental (MMSE) scores. The main results depict a strong relationship between MMSE and WAY2AGE scores, as well as a good AUC value to discriminate between no cognitive impairment (NCI) and MCI groups. However, a relationship between age and WAY2AGE scores, but not between age and MMSE scores, was found. This would indicate that, even if WAY2AGE seems sensitive to detect MCI, the voice tool is age-sensitive and not as robust as the traditional MMSE scale. Future lines of research should look more deeply into parameters that distinguish developmental changes. As a screening tool, these results are of interest for the health area and for at-risk older adults.
Canadian women in otolaryngology: Head and neck surgery part 2—challenges in family planning, fertility, and lactation
Authors: Naismith Kendra , Ioanidis Khrystyna , Dzioba Agnieszka , MacNeil S. Danielle , Paradis Josee , Nayan Smriti , Strychowsky Julie E. , Graham M. Elise
Published: May 2023

Background

Previous literature demonstrates that female surgeons face difficulties in family planning, meeting breastfeeding goals, leadership and advancement opportunities. These issues have received limited attention in Canadian surgeons despite different maternity leave patterns compared to the general Canadian population. We sought to describe the experience of otolaryngologist-head and neck surgeons in family planning, fertility, and lactation and to identify the role of gender and career stage in these experiences.

Methods

A RedCAP® survey was disseminated to Canadian otolaryngology–head and neck surgeons and residents from March to May of 2021 through social media and the national listserv. This survey examined fertility, pregnancy losses, and infant feeding. Major independent variables include gender and career stage (faculty and resident). Dependent variables include respondent experiences with fertility, number of children, and length of parental leave. Responses were tabulated and presented descriptively to communicate the experience of Canadian otolaryngologists. Further, statistical comparisons such as chi-square and t-tests were employed to identify relationships between these variables. Thematic analysis was conducted for narrative comments.

Results

We received 183 completed surveys (22% response rate). 54% of females versus 13% of males agreed that career influenced their ability to have children ( p = 0.002). 74% of female respondents without children have concerns about future fertility compared to 4% of men ( p < 0.001). Furthermore, 80% of women versus 20% of men have concerns about future family planning ( p < 0.001). The average maternity leave was 11.5 weeks for residents, and 22.2 weeks for staff. Additionally, significantly more women than men stated that maternity leave impacted advancement opportunities (32% vs. 7%) and salary/remuneration (71% vs. 24%) ( p < 0.001). Over 60% of those choosing to pump breastmilk at work reported having inadequate time, space, and breastmilk storage. In total, 62% of breastfed infants were receiving breastmilk at 1 year.

Conclusion

Canadian female otolaryngologists-head and neck surgeons face challenges in family planning, ability to conceive, and breastfeeding. Focused effort is required to provide an inclusive environment that helps all otolaryngologists-head and neck surgeons achieve both their career and family goals, regardless of gender or career stage.

Graphical Abstract
Safety injections of nuclear medicine radiotracers: towards a new modality for a real-time detection of extravasation events and 18F-FDG SUV data correction
Authors: Iori Mauro , Grassi Elisa , Piergallini Lorenzo , Meglioli Greta , Botti Andrea , Sceni Giada , Cucurachi Noemi , Verzellesi Laura , Finocchiaro Domenico , Versari Annibale , Fraboni Beatrice , Fioroni Federica
Published: May 2023

Background

18F-FDG PET/CT imaging allows to study oncological patients and their relative diagnosis through the standardised uptake value (SUV) evaluation. During radiopharmaceutical injection, an extravasation event may occur, making the SUV value less accurate and possibly leading to severe tissue damage. The study aimed to propose a new technique to monitor and manage these events, to provide an early evaluation and correction to the estimated SUV value through a SUV correction coefficient.

Methods

A cohort of 70 patients undergoing 18F- FDG PET/CT examinations was enrolled. Two portable detectors were secured on the patients' arms. The dose-rate (DR) time curves on the injected DRin and contralateral DRcon arm were acquired during the first 10 min of injection. Such data were processed to calculate the parameters ΔpinNOR = (DRinmax- DRinmean)/DRinmax and ΔRt = (DRin(t) − DRcon(t)), where DRinmax is the maximum DR value, DRinmean is the average DR value in the injected arm. OLINDA software allowed dosimetric estimation of the dose in the extravasation region. The estimated residual activity in the extravasation site allowed the evaluation of the SUV's correction value and to define an SUV correction coefficient.

Results

Four cases of extravasations were identified for which ΔRt [(390 ± 26) µSv/h], while ΔRt [(150 ± 22) µSv/h] for abnormal and ΔRt [(24 ± 11) µSv/h] for normal cases. The ΔpinNOR showed an average value of (0.44 ± 0.05) for extravasation cases and an average value of (0.91 ± 0.06) and (0.77 ± 0.23) in normal and abnormal classes, respectively. The percentage of SUV reduction (SUV%CR) ranges between 0.3% and 6%. The calculated self-tissue dose values range from 0.027 to 0.573 Gy, according to the segmentation modality. A similar correlation between the inverse of ΔpinNOR and the normalised ΔRt with the SUV correction coefficient was found.

Conclusions

The proposed metrics allowed to characterised the extravasation events in the first few minutes after the injection, providing an early SUV correction when necessary. We also assume that the characterisation of the DR-time curve of the injection arm is sufficient for the detection of extravasation events. Further validation of these hypotheses and key metrics is recommended in larger cohorts.
Feasibility and pilot study of passive heat therapy on cardiovascular performance and laboratory values in older adults
Authors: Flynn Brigid , Vitztum Michelle , Miller Joshua , Houchin Abigail , Kim Jaromme , He Jianghua , Geiger Paige
Published: May 2023

Background

Chronic heat therapy may have beneficial effects on cardiovascular function. These effects may be more pronounced in older adults. We performed a pilot feasibility study of repeated heat therapy sessions in a hot tub (40.5 °C) in older adults while wearing a noninvasive hemodynamic monitor. As part of the protocol, the volunteers underwent cardiovascular performance testing pre- and post-intervention.

Methods

Fifteen volunteers > 50 years old underwent 8–10 separate 45-min hot tub session over 14 days in this exploratory and mixed methods trial. The participants had maximal oxygen consumption (VO2 max) and other cardiovascular data measured via exercise treadmill testing prior to and after all hot tub sessions. The participants also wore noninvasive fingertip volume clamp monitors while immerged in hot water that calculated systemic vascular resistance, heart rate, blood pressure, and cardiac output in order to ascertain the feasibility and utility of this data. Other laboratory studies were obtained pre- and post-intervention. The protocol was determined feasible if the heat therapy and cardiovascular testing was completed by at least 90% (14/15 subjects). Feasibility of the noninvasive monitor was determined by the fidelity of the results. Secondary exploratory outcomes were analyzed for differences to identify if they are acceptable to include in an efficacy trial.

Results

All participants completed the study protocol identifying the feasibility of the protocol. The noninvasive hemodynamic monitors successfully recorded cardiac output, systemic vascular resistance, heart rate, and blood pressure with fidelity based on the analysis of recordings. In the secondary analyses, we found no difference in the pre- to post-intervention measurement of VO2 max but did find increased exercise duration following hot tub therapy compared with prior to the therapy (571 s versus 551 s).

Conclusions

The current pilot study protocol is feasible for the purpose of analyzing the effects of heat therapy and cardiovascular performance in older adults while wearing a noninvasive hemodynamic monitor and undergoing treadmill stress testing. Secondary analyses found increased exercise tolerance but no differences in VO2 max following heat sessions.
Self-reported adverse events associated with ∆8-Tetrahydrocannabinol (Delta-8-THC) Use
Authors: Leas Eric C. , Harati Raquel M. , Satybaldiyeva Nora , Morales Nicolas E. , Huffaker Shelby L. , Mejorado Tomas , Grant Igor
Published: May 2023

Background

There is an expanding unregulated market for a psychotropic compound called ∆8-Tetrahydrocannabinol (delta-8-THC) that is being derived from hemp, but a summary of adverse events related to delta-8-THC has not been publicly reported.

Methods

This case series assessed adverse events reported by delta-8-THC users on the Reddit forum r/Delta8 and compared these to delta-8-THC AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). Delta-8-THC and cannabis AEs reported in FAERS were also compared. The r/Delta8 forum was selected because it includes a large sample of 98,700 registered individuals who publicly discuss their experiences using delta-8-THC. All r/Delta8 posts were obtained from August 20, 2020, through September 25, 2022. A random sample of r/Delta8 posts was drawn (n = 10,000) and filtered for posts in which delta-8-THC users reported an adverse event (n = 335). FAERS reports that listed delta-8-THC (N = 326) or cannabis (N = 7076) as a suspect product active ingredient were obtained. Adverse events claimed to result from delta-8-THC use were coded using Medical Dictionary for Regulatory Activities to system organ class and preferred term categories.

Results

The absolute number of delta-8-THC adverse event reports (N = 2184, 95% CI = 1949–2426) and serious adverse event reports (N = 437; 95% CI = 339–541) on r/Delta 8 were higher than the adverse event reports (N = 326) and serious adverse event reports (N = 289) to FAERS. Psychiatric disorders were the most frequently cited system organ class in r/Delta8 adverse event reports, mentioned in 41.2% (95% CI = 35.8%-46.3%) of reports, followed by respiratory, thoracic and mediastinal disorders (29.3%, 95% CI = 25.1%-34.0%) and nervous system disorders (23.3%, 95% CI = 18.5%-27.5%). Anxiety (16.4%, 95% CI = 12.8–20.6), Cough (15.5%, 95% CI = 11.9–20.0) and Paranoia (9.3%, 95% CI = 6.3–12.5) were the most frequently cited preferred terms in adverse event reports. The overall prevalence of AEs reported for cannabis and delta-8-THC on FAERS were also similar when analyzed by system organ class (Pearson’s r = 0.88).

Conclusions

The findings of this case series suggest that most of the adverse events reported by delta-8-THC users are like those reported during acute cannabis intoxication. This finding suggests that health care professionals follow similar treatment and management protocols, and that jurisdictions should clarify whether delta-8-THC can be sold as a hemp product.
Fire severity influences large wood and stream ecosystem responses in western Oregon watersheds
Authors: Coble Ashley A. , Penaluna Brooke E. , Six Laura J. , Verschuyl Jake
Published: May 2023

Background

Wildfire is a landscape disturbance important for stream ecosystems and the recruitment of large wood (LW; LW describes wood in streams) into streams, with post-fire management also playing a role. We used a stratified random sample of 4th-order watersheds that represent a range of pre-fire stand age and fire severity from unburned to entirely burned watersheds to 1) determine whether watershed stand age (pre-fire) or fire severity affected riparian overstory survival, riparian coarse wood (CW; CW describes wood in riparian areas), LW, or in-stream physical, chemical, and biological responses; and 2) identify relationships of LW with riparian vegetation and in-stream physical, chemical, and biological factors.

Results

At higher fire severities, LW and CW diameter was smaller, but volume did not change in the first year post-fire. Larger size of CW in riparian areas versus LW in streams suggests potential future recruitment of larger-diameter wood into streams from riparian zones in severely burned watersheds. Fire severity exerted strong control on stream responses across watersheds, explaining more of the variation than stand age. At higher fire severities, riparian tree mortality, salvage logging, light, dissolved organic matter (DOM) concentrations, and fish densities were higher, whereas canopy cover, LW diameter, macroinvertebrate diversity, and amphibian density were lower. In watersheds with older stand ages, elevation and mean annual precipitation were greater but mean annual temperature, specific ultra-violet absorption at 254 nm, and phosphorus concentrations were lower. Overstory mortality in burned riparian areas was lower for red alder (12%) than western redcedar (69%).

Conclusions

Our results link forested streams, fire, and LW by identifying key relationships that change with fire severity and/or watershed stand age. Severe fires burn more overstory riparian vegetation, leading to increased light, DOM concentrations, and macroinvertebrate and fish densities, along with reduced canopy cover, LW diameter, macroinvertebrate diversity, and amphibian densities. We highlight an important function of red alder in riparian zones—as a fire-resistant species, it may help facilitate a more rapid recovery for streams in fire-prone landscapes. Continued comprehensive aquatic and riparian ecosystem monitoring of these watersheds will aid in understanding long-term effects of post-fire management activities (salvage logging) on aquatic ecosystems.
Treatment with succinate dehydrogenase inhibitor Y12196 protects strawberries from boscalid-resistant Botrytis cinerea with the H272R mutation in SDH B
Authors: Wu Jianyan , Mao Hanxin , Sun Yanan , Wei Fanglin , Wang Hancheng , Zhang Chuanqing
Published: May 2023

Gray mold, caused by Botrytis cinerea, poses a significant threat to the strawberry industry worldwide. B. cinerea is a high-risk pathogen in the sense of fungicide resistance. The sensitivities of B. cinerea isolates collected from Zhejiang Province, China, to the succinate dehydrogenase inhibitors (SDHIs) boscalid and Y12196 were determined based on discriminatory dose or 50% effective concentration (EC50). Of the 42 isolates collected in 2018, 15 were resistant to boscalid (35.7%), and 3 were resistant to Y12196 (7.1%). Among the 84 isolates collected in 2019, the EC50 values for boscalid ranged from 0.097 to 54.162 mg/L, while the EC50 values for Y12196 ranged from 0.284 to 20.147 mg/L. Sequence analysis showed that the B. cinerea isolates carrying P225F (proline → phenylalanine) and N230I (asparagine → isoleucine) mutations in SDH subunit B exhibited cross-resistance between boscalid and Y12196. However, boscalid-resistant isolates with a point mutation at position 272 of SDH B (H272R, histidine → arginine) were more sensitive to Y12196. Consistent with this, Y12196, but not boscalid, could successfully inhibit the growth of B. cinerea carrying the H272R mutation (BcSDHB−H272R) on detached strawberries and leaves. Molecular docking simulations further revealed that the hydrogen bonds and π-π interactions were formed between Y12196 and BcSDHB−H272R, but not between boscalid and BcSDHB−H272R, explaining why the boscalid-resistant B. cinerea H272R mutant isolates were sensitive to Y12196. Together, our results suggested that Y12196 could effectively control boscalid resistance associated with the H272R mutation.
Fresh versus frozen embryo transfer in women with polycystic ovaries syndrome undergoing in vitro fertilisation
Authors: Hussein Mohamed , Sayed Abdullah , Eldaly Ashraf , AlSawaf Ahmed H. , Eid Marwa M. , Abdel-Rasheed Mazen , Rashwan Ahmed S.
Published: May 2023

Background

Polycystic ovarian syndrome (PCOS) cases undergoing in vitro fertilisation (IVF) are widely at risk of ovarian hyperstimulation; therefore, elective freezing of all embryos to be transferred in a later cycle is preferred. We aimed to compare the pregnancy outcome between the fresh and the frozen embryo transfer (ET) in PCOS cases undergoing IVF with antagonist ovarian induction using human chorionic gonadotropin (HCG) as a trigger.

Methods

In this prospective randomised study, 110 infertile PCOS women underwent fresh ET (group A) or frozen ET (group B) with GnRH-antagonist protocol. The primary outcome was the chemical and clinical pregnancy rates. The secondary outcomes were the ongoing pregnancy rate, ovarian hyperstimulation syndrome (OHSS) rate, pregnancy loss rate, ectopic pregnancy rate, and congenital anomalies rate.

Results

There was no significant difference between both groups regarding chemical pregnancy rate (44.23% vs 47.27%, P = 0.752), clinical pregnancy rate (42.31% vs 43.64%, P = 0.89), ongoing pregnancy rate (38.46% vs 41.82%, P = 0.723), pregnancy loss rate (17.39% vs 15.4%, P = 1), ectopic pregnancy rate (1.92% vs 0%, P = 0.486) and anomaly malformation rate (4.35% vs 3.85%, P = 1). On the other hand, the incidence of OHSS was significantly less in group B than in group A (3.64% vs 19.23%, P = 0.011), and the OHSS grade was less severe in group B than in group A (P = 0.033). However, there was no statistically significant difference between both regarding the need for hospitalisation (P = 0.111), ICU admission (P = 0.486), and ascites tapping (P = 0.486).

Conclusions

Under GnRH-antagonist protocol, frozen ET has the upper hand in PCOS undergoing IVF treatment for infertility, as it protects against OHSS and decreases its severity.

Trial registration

It was first registered at ClinicalTrials.gov on 22/12/2021 with registration number NCT05167838.
Apical but not basal RV strain reflects right ventricular dysfunction in patients with dilated cardiomyopathy
Authors: Ali Asmaa Ahmed , Mohammed Safaa Abo Alfadl , Hamdy Amal Mohamed
Published: May 2023

Background

RV dysfunction is an important predictor of morbidity and mortality in cardiac patients, especially those having dilated cardiomyopathy (DCM). Deformation imaging parameters (strain and strain rate) are established as new echocardiographic measures that allow for both global and regional RV function assessment. Previous studies showed that heterogeneous segmental deformation affects global RV function differently in various disease states. Echo-Doppler parameters of RV and LV function including RV global longitudinal strain, basal & apical RV strain, LV ejection fraction and LV global longitudinal strain were evaluated in 42 DCM patients & 28 normal subjects, aiming to assess the value of apical versus basal RV strain in detection of RV dysfunction in patients with dilated cardiomyopathy.

Results

DCM patients had significantly lower values of both RV global longitudinal strain and apical RV strain compared to normal subjects (p < 0.001). Basal RV strain did not significantly differ in DCM from normal. The apical RV strain correlated significantly with RV global longitudinal strain, LV ejection fraction and LV global longitudinal strain (p < 0.001 for all). Using ROC curve, a cut-off value of apical RV strain ≤ 29.5 distinguished RV dysfunction from normal with 91.2% sensitivity & 100% specificity.

Conclusions

RV apical but not basal strain reflects the status of RV function, and it represents a valuable measure to diagnose RV dysfunction in patients with DCM.
Application of The Consolidated Framework for Implementation Research to inform understanding of barriers and facilitators to the implementation of opioid and naloxone training on college campuses
Authors: Shelton Rachel C. , Goodwin Kathleen , McNeil Michael , Bernitz Melanie , Alexander Savannah P. , Parish Carrigan , Brotzman Laura , Lee Matthew , Li WaiKwan , Makam Supriya , Ganek Nicholas , Foskett Dean , Warren Chloe , Metsch Lisa R.
Published: May 2023

Background

The opioid epidemic in the US continues to worsen. Opioid-only and polysubstance-involved opioid overdose deaths are increasing among adolescents and young adults, who have limited knowledge of opioid overdose prevention, including recognition and response. College campuses have infrastructure to support national-level implementation of evidence-based public health strategies for providing opioid overdose prevention and naloxone training programs among this priority population. However, college campuses are an underutilized, understudied setting for this programming. To address this gap, we conducted research assessing barriers and facilitators to planning and implementing this programming on college campuses.

Methods

We held 9 focus groups among purposively selected campus stakeholders whose perceptions were important to understand in planning for the dissemination and implementation of opioid overdose prevention and naloxone training. Focus group scripts were informed by The Consolidated Framework for Implementation Research (CFIR) to query about perceptions of opioid and other substance use, opioid and other substance use-related resources, and naloxone administration training. We used a deductive-inductive, iterative approach to thematic analysis.

Results

Themes about implementation barriers included (1) the perception that problematic use of other (non-opioid) substances was more prevalent than opioid use on campus and focus on those substances would be a greater priority on college campuses; (2) student schedules were overwhelmed with academic commitments and extracurricular activities, making delivery of additional training challenging; (3) barriers related to the perceived complexity and decentralization of communication on campus, preventing students from knowing how to access substance use-related resources. Themes about implementation facilitators included (1) framing naloxone training as important in becoming a responsible leader on campus and in the broader community and (2) leveraging existing infrastructure, champions within existing campus groups, and tailored messaging to facilitate participation in naloxone training.

Conclusions

This is the first study to provide in-depth insights into potential barriers and facilitators to widespread, routine implementation of naloxone/opioid education on undergraduate college campuses. The study captured diverse stakeholder perspectives and was theoretically grounded in CFIR, contributing to the growing literature on the application and refinement of CFIR across diverse community and school contexts.
Impact of e-service quality on e-loyalty of online banking customers in Pakistan during the Covid-19 pandemic: mediating role of e-satisfaction
Authors: Khan Fahad Najeeb , Arshad Muhammad Usman , Munir Muhammad
Published: May 2023

This study explores the mediating role of e-satisfaction during the pandemic on the relationship between e-service quality and e-loyalty of banking customers in Pakistan. The data were collected from 442 customers of online banking services in Pakistan during the Covid-19 pandemic, following a survey-based study. Baron and Kenny (J Personal Soc Psychol, 51(6):1173, 1986) and Preacher and Hayes (Behav Res Methods, 40(3):879-891, 2008) mediation technique which utilizes the bootstrapping method has been used to explore mediation. The findings show that e-service quality has a significant positive effect on the e-loyalty of the customers of online banking services. Relationships between e-service quality and e-loyalty of online banking customers in Pakistan are significantly and fully mediated by their online satisfaction in unusual situations. This study would help the bankers to implement more effective marketing strategies to retain their customers and attract potential customers, particularly during non-normal situations like the Covid-19 pandemic. It will help them identify the areas of e-services that need improvement to enhance the satisfaction and loyalty of the customers. The bootstrap method for mediation along with Baron and Kenny (J Personal Soc Psychol, 51(6):1173, 1986) leads to using a more sophisticated methodological technique to explore the mediation. The Oliver Expectancy-Disconfirmation Paradigm (EDP) in electronic banking setup during non-normal situations like the Covid-19 pandemic also served as a unique contribution to this study. Application of Baron and Kenny (J Personal Soc Psychol, 51(6):1173, 1986) mediation along with Preacher and Hayes (Behav Res Methods, 40(3):879-891, 2008) leads to more robust findings for the study in non-normal situations like the Covid-19 pandemic. The study findings add scientific value as they are applicable to the banking sector in particular in non-normal situations like the Covid-19 pandemic and the overall service sector in general. Further, as two different methods of mediation have been employed and this makes the study more rigorous and scientific.
Euthanasia and physician-assisted suicide in people with intellectual disabilities and/or autism spectrum disorders: investigation of 39 Dutch case reports (2012–2021)
Authors: Tuffrey-Wijne Irene , Curfs Leopold , Hollins Sheila , Finlay Ilora
Published: May 2023

Background

Euthanasia review committees (Regionale Toetsingscommissies Euthanasie, RTE) scrutinise all Dutch cases of euthanasia and physician-assisted suicide (EAS) to review whether six legal ‘due care’ criteria are met, including ‘unbearable suffering without prospect of improvement’. There are significant complexities and ethical dilemmas if EAS requests are made by people with intellectual disabilities or autism spectrum disorders (ASD).

Aims

To describe the characteristics and circumstances of people with intellectual disabilities and/or ASD who were granted their EAS request; investigate the main causes of suffering that led to the EAS request; and examine physicians’ response to the request.

Method

The online RTE database of 927 EAS case reports (2012–2021) was searched for patients with intellectual disabilities and/or ASD (n = 39). Inductive thematic content analysis was performed on these case reports, using the framework method.

Results

Factors directly associated with intellectual disability and/or ASD were the sole cause of suffering described in 21% of cases and a major contributing factor in a further 42% of cases. Reasons for the EAS request included social isolation and loneliness (77%), lack of resilience or coping strategies (56%), lack of flexibility (rigid thinking or difficulty adapting to change) (44%) and oversensitivity to stimuli (26%). In one-third of cases, physicians noted there was ‘no prospect of improvement’ as ASD and intellectual disability are not treatable.

Conclusions

Examination of societal support for suffering associated with lifelong disability, and debates around the acceptability of these factors as reasons for granting EAS, are of international importance.
Maternally Inherited Diabetes and Deafness (MIDD) – Atypical Clinical Diabetes Features Leading to the Diagnosis
Authors: Kyriakidou Anna , Hadjivassiliou Marilena , Papapostolou Anastasia , Picolos Michalis K
Published: May 2023

Maternally inherited diabetes and deafness (MIDD) syndrome refers to a rarely diagnosed disorder caused by pathogenic variants in mtDNA. It was first identified in 1992 and, to date, is considered underdiagnosed because of misclassification to type 1 or type 2 diabetes mellitus. MIDD reflects a multisystem metabolic syndrome commonly resulting in insulin-requiring diabetes and sensorineural deafness but can also lead to a broad range of other manifestations. The spectrum of pathology differs among individuals, likely because of varied degrees of heteroplasmy associated with mtDNA. Heteroplasmy also creates diagnostic difficulties, with a high index of suspicion required to diagnose MIDD in some cases. Here, we review a patient with MIDD who presented with an atypical clinical diabetes picture, additionally documenting his pedigree. To our knowledge, this is the first Cypriot reported with MIDD.
Radiofrequency Ablation of Cervical Thyroid Cancer Metastases—Experience of Endocrinology Practices in the United States
Authors: Ahmad Shahzad , Aljammal Jules , Orozco Ian , Raashid Sheharyar , Zulfiqar Fizza , Nikravan Sean P , Hussain Iram
Published: May 2023

Context

Radiofrequency ablation (RFA) is used in the United States to treat benign thyroid nodules; however, experience with treating cervical recurrence/persistence of papillary thyroid cancer (PTC) is limited.

Objective

To evaluate the efficacy RFA for the treatment of cervical recurrence/persistence of PTC in the United States.

Methods

This is a retrospective, multicenter study of 8 patients who underwent RFA of 11 cervical metastatic PTC lesions between July 2020 and December 2021. The volume reduction (VR) of the lesions, thyroglobulin (Tg) levels and complications following RFA were assessed. Energy applied per unit volume (E/V) during RFA was also determined.

Results

Nine out of 11 (81.8%) lesions had initial volume under 0.5 mL and showed a complete (n = 8) or near-complete (n = 1) response. The 2 lesions with initial volume over 1.1 mL had a partial response, 1 of which had regrowth. There was a median VR of 100% (range 56.3-100%) after a median follow-up period of 453 days (range 162-570 days), with corresponding decline in Tg levels from a median of 0.7 ng/mL (range 0-15.2 ng/mL) to a median of 0.3 ng/mL (range 0-1.3 ng/mL). All patients with an E/V of at least 4483 J/mL or higher had a complete or near-complete response. There were no complications.

Conclusion

RFA performed in an endocrinology practice is an efficacious treatment option for selected patients with cervical metastases of PTC, particularly those who cannot or do not want to undergo further surgery.
Thoracic Epidural Anesthesia in Cardiac Surgery: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Chiew John Keong , Low Christopher Jer Wei , Zeng Kieran , Goh Zhi Jie , Ling Ryan Ruiyang , Chen Ying , Ti Lian Kah , Ramanathan Kollengode
Published: May 2023

BACKGROUND:

Research on fast-track recovery protocols postulates that thoracic epidural anesthesia (TEA) in cardiac surgery contributes to improved postoperative outcomes. However, concerns about TEA’s safety hinder its widespread usage. We conducted a systematic review and meta-analysis to assess the benefits and risks of TEA in cardiac surgery.

METHODS:

We searched 4 databases for randomized controlled trials (RCTs) assessing the use of TEA against only general anesthesia (GA) in adults undergoing cardiac surgery, up till June 4, 2022. We conducted random-effects meta-analyses, evaluated risk of bias using the Cochrane Risk-of-Bias 2 tool, and rated certainty of evidence via the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Primary outcomes were intensive care unit (ICU), hospital length of stay, extubation time (ET), and mortality. Other outcomes included postoperative complications. Trial sequential analysis (TSA) was conducted on all outcomes to elicit statistical and clinical benefit.

RESULTS:

Our meta-analysis included 51 RCTs (2112 TEA patients and 2220 GA patients). TEA significantly reduced ICU length of stay (−6.9 hours; 95% confidence interval [CI], −12.5 to −1.2; P = .018), hospital length of stay (−0.8 days; 95% CI, −1.1 to −0.4; P < .0001), and ET (−2.9 hours; 95% CI, −3.7 to −2.0; P < .0001). However, we found no significant change in mortality. TSA found that the cumulative Z-curve passed the TSA-adjusted boundary for ICU length of stay, hospital length of stay, and ET, suggesting a clinical benefit. TEA also significantly reduced pain scores, pooled pulmonary complications, transfusion requirements, delirium, and arrhythmia, without additional complications such as epidural hematomas, of which the risk was estimated to be <0.14%.

CONCLUSIONS:

TEA reduces ICU and hospital length of stay, and postoperative complications in patients undergoing cardiac surgery with minimal reported complications such as epidural hematomas. These findings favor the use of TEA in cardiac surgery and warrant consideration for use in cardiac surgeries worldwide.
The Wage Phillips Curve under Labor Market Power
Authors: Burya Anastasia , Mano Rui , Timmer Yannick , Weber Anke
Published: May 2023

Using the near universe of online vacancy postings in the United States, we explore linkages between labor market power and the trade-off between unemployment and wages. We estimate the Phillips curve at the commuting zone level and find that the relationship between unemployment and wage inflation is weak in regions with high labor market power. These results help explain the flattening of the wage Phillips curve following the global financial crisis. In the context of rising interest rates, unemployment is likely to rise more in poorer US regions because labor market power is more prevalent there, thus leading to rising inequality.
Measuring Work from Home in the Cross Section
Authors: Kmetz Augustus , Mondragon John , Wieland Johannes F.
Published: May 2023

We compare survey-based measures of work from home (WFH) in the cross section. While the surveys differ in how comprehensively they measure WFH, they are highly correlated in the cross section of US states, suggesting that they will yield similar causal effects. Researchers should carefully consider the trade-off between how comprehensively WFH is measured and measurement error, with the American Community Survey well suited for low levels of aggregation and the Survey of Working Arrangements and Attitudes and Real-Time Population Survey well suited to measuring distinct types of WFH. We also document that the experimental 2020 ACS replicate weights produce errors that are too small.
Least Protected, Most Affected: Impacts of Migration Regularization Programs on Pandemic Resilience
Authors: Urbina Maria José , Rozo Sandra V. , Moya Andrés , Ibáñez Ana María
Published: May 2023

How can regularization programs improve forced migrants' resilience to shocks? We leverage panel data collected during the COVID-19 pandemic to assess whether Venezuelan forced migrants who were eligible for a regularization program in Colombia were more resilient and less affected by the pandemic than similar but noneligible forced migrants. Results indicate that access to the program promoted better health access for eligible migrants, facilitating adherence to prevention guidelines and increasing detection rates. Additionally, eligible migrants had better housing and labor conditions, relative to noneligible migrants.