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Background: To prevent deterioration after admission to the intensive care unit (ICU), and to improve rehabilitation, the ICU team should use digital technologies to provide comprehensive and practical information alongside personalised support for survivors and their family members. However, a knowledge gap exists on the users' preferences for such an e-health platform in ICU follow-up services., Objectives: This study aims to explore the opinions and priorities for an e-health platform, including choices in digital elements, according to survivors of critical illness and their family members., Methods: A cross-sectional survey was used among members and other interested individuals of the Dutch volunteer organisation 'Foundation Family- and Patient-Centred Intensive Care'. An investigator-developed questionnaire was disseminated through the newsletter and social media channels of the Foundation Family- and Patient-Centred Intensive Care. The results of this member consultation were analysed and reported as descriptive statistics on demographic variables and outcome measures in opinions and priorities of the participants., Results: Most of the 227 participants were female (76%), aged 46-55 years (33%), and completed higher education (70%). The participants reported high confidence in advice delivered through an e-health platform (72%). They prioritised the provision of a guide including relevant professionals who may support them during their recovery when using an e-health platform., Conclusions: ICU survivors prioritised the provision of relevant professionals who may support them during their recovery when using an e-health platform; however, selection bias means the population studied is likely to be more digitally connected than the general ICU population. Digital solutions could cater to their information and support needs. For family members, the highest priority reported was receiving help in managing their emotional distress. The development of an e-health platform considering the opinions and priorities of this target group could contribute to a personalised recovery trajectory promoting self-management while including digital elements addressing relevant ICU follow-up services., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Reliable and recent data of human rabies deaths and animal bites are not available in India, where a third of global cases occur. Since there is a global target of eliminating dog-mediated human rabies by 2030, understanding whether the country is on track is essential. We aimed to estimate the animal-bite burden and the number of human rabies deaths in India., Methods: We conducted a community-based nationwide cross-sectional survey with a multistage cluster-sampling design from March 2, 2022 to Aug 26, 2023, covering 60 districts in 15 Indian states. The head of the household or an adult family member was interviewed to collect information about animal-bite history in family members, receipt of anti-rabies vaccination (ARV), and death following animal bite in the family. Annual animal-bite incidence along with 95% CIs were estimated after applying the sampling weights and adjusting for clustering. We estimated annual human rabies deaths using a decision-tree probability model with parameters from the community survey and laboratory data on rabies positivity among suspected rabid dogs., Findings: Of the 337 808 individuals residing in the 78 807 households surveyed, 2052 gave a history of animal bite, mostly (1576 [76·8%]) due to dogs in the past 1 year. The weighted and adjusted annual incidence of animal bite was 6·6 (95% CI 5·7-7·6) per 1000 population, translating into 9·1 million bites nationally. Annual dog-bite incidence was 5·6 (4·8-6·6) per 1000. Among people who had been bitten by a dog, 323 (20·5%) did not receive ARV, and 1043 (66·2%) received at least three doses. Nearly half (615 [49·1%]) of the 1253 individuals who received one dose did not complete their full course of vaccination. We estimated 5726 (95% uncertainty interval 3967-7350) human rabies deaths occurring annually in India., Interpretation: Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal., Funding: Indian Council of Medical Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

This study investigates the role of emotional attachment to competing institutional logics on women's uptake of cervical cancer screening in Mozambique. Through a qualitative study conducted in Xai-Xai, Southern Mozambique, we identify 2 concurrent logics in the context of screening: preservation logic, influenced by social-cultural norms, and the prevention logic, centered around screening. Women, affected by emotions such as shame, fear, and marital subordination, often become attached to the preservation logic, which influences their values and contradicts acceptance of screening. However, some women with marital autonomy may reflect on both logics and gradually detach themselves from the preservation norms and show their intention to adopt life-saving behavior by accepting screening. It is through their emotions that women show their attachment to and detachment from competing logics, reinforcing traditional norms on the one hand, or giving them the means to adopt preventive measures on the other. The study indicates that cultural expectations, shame and the desire to preserve intimacy tie women to the logic of preservation and have a negative impact on participation in cervical cancer screening. Consequently, to improve screening uptake in Mozambique, the authorities need to adapt screening to socio-cultural and emotional factors, empower women, and effectively engage communities., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

This study evaluates the accuracy and repeatability of craniofacial measurements with a 3D light scanner, specifically the EINSTAR scanner, in comparison to traditional caliper measurements for facial anthropometry. Eleven volunteers were assessed by two examiners, one experienced and one inexperienced, who performed direct caliper measurements and indirect measurements using the scanner. Results indicated minimal differences between caliper and scanner results, with overall high accuracy and reliability demonstrated by correlation coefficients. Despite the slightly longer scanning time, the benefits of 3D imaging, including detailed surface mapping and virtual modeling, justify its integration into clinical practice, particularly in maxillofacial surgery and craniofacial assessment. Craniofacial measurements obtained with the EINSTAR scanner showed excellent reliability and accuracy, which qualifies this method for clinical and scientific use.

Purpose: Multiple studies have explored the needs and experiences of patients, family members, and healthcare professionals regarding hospital-to-home transitions. Our study aimed to identify, critically appraise, and summarize these studies in a qualitative meta-synthesis., Materials and Methods: Medline, CINAHL and Embase were systematically searched to identify eligible articles from inception to June 2024. Qualitative studies were included and critically appraised using the Critical Appraisal Skills Program. Insufficient-quality papers were excluded. We performed a meta-synthesis following (1) open coding by two independent researchers and (2) discussing codes during reflexivity meetings., Results: Ninety-eight studies were appraised, of which 53 were included. We reached thematic saturation, four themes were constructed: (1) care coordination and continuity, (2) communication, (3) patient and family involvement, and (4) individualized support and information exchange. For patients and families, tailored information and support are prerequisites for a seamless transition and an optimal recovery trajectory after hospital discharge. It is imperative that healthcare professionals communicate effectively within and across care settings to ensure multidisciplinary collaboration and care continuity., Conclusions: This study identifies essential elements of optimal transitional care. These findings could be supportive to researchers and healthcare professionals when (re)designing transitional care interventions to ensure care continuity after hospital discharge.

Background: This protocol describes a realist review exploring the problem of "missingness" in healthcare, defined as the repeated tendency not to take up offers of care that has a negative impact on the person and their life chances. More specifically, the review looks at the phenomenon of patients missing multiple appointments in primary care in the UK - at the causal factors that influence how patients come to be "missing" in this way, and what interventions might support uptake and "presence" in healthcare. Background research informing this project suggests that a high rate of missed appointments predicted high premature death rates, and patients were more likely to have multiple long-term health conditions and experience significant socioeconomic disadvantage. Most research in this field focuses on population- or service-level characteristics of patients who miss appointments, often making no distinction between causes of single missed appointments and of multiple missed appointments. There have therefore been no interventions for 'missingness', accounting for the complex life circumstances or common mechanisms that cause people to repeatedly miss appointments., Methods: We use a realist review approach to explore what causes missingness - and what might prevent or address it - for whom, and in what circumstances. The review uses an iterative approach of database searching, citation-tracking and sourcing grey literature, with selected articles providing insight into the causal dynamics underpinning missed appointments and the interventions designed to address them., Discussion: The findings of this review will be combined with the findings of a qualitative empirical study and the contributions of a Stakeholder Advisory Group (STAG) to inform the development of a programme theory that seeks to explain how missingness occurs, whom it affects and under what circumstances. This will be used to develop a complex intervention to address multiple missed appointments in primary care., Prospero Registration: CRD42022346006., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Lindsay C et al.)

Borrelia burgdorferi sensu lato (Bb) are a complex of bacteria genospecies that can cause Lyme disease (LD) in humans after the bite of an infected Ixodes spp. vector tick. In Canada, incidence of LD is increasing in part due to the rapid geographic expansion of Ixodes scapularis across the southcentral and eastern provinces. To better understand temporal and spatial (provincial) prevalence of Bb infection of I. scapularis and how tick surveillance is utilized in Canada to assess LD risk, a literature review was conducted. Tick surveillance studies published between January 1975 to November 2023, that measured the prevalence of Bb in I. scapularis via "passive surveillance" from the public citizenry or "active surveillance" by drag or flag sampling of host-seeking ticks in Canada were included for review. Meta-analyses were conducted via random effects modeling. Forty-seven articles, yielding 26 passive and 28 active surveillance studies, met inclusion criteria. Mean durations of collection for I. scapularis were 2.1 years in active surveillance studies (1999-2020) and 5.5 years by passive surveillance studies (1990-2020). Collectively, data were extracted on 99,528 I. scapularis nymphs and adults collected between 1990-2020 across nine provinces, including Newfoundland & Labrador (33 ticks) and Alberta (208 ticks). More studies were conducted in Ontario (36) than any other province. Across nine provinces, the prevalence of Bb infection in I. scapularis collected by passive surveillance was 14.6% with the highest prevalence in Nova Scotia at 20.5% (minimum studies >1). Among host-seeking I. scapularis collected via active surveillance, Bb infection prevalence was 10.5% in nymphs, 31.9% in adults, and 23.8% across both life stages. Host-seeking I. scapularis nymphs and adults from Ontario had the highest Bb prevalence at 13.6% and 34.8%, respectively. Between 2007-2019, Bb infection prevalence in host-seeking I. scapularis was positively associated over time (p<0.001) which is concurrent with a ∼25-fold increase in the number of annually reported LD cases in Canada over the same period. The prevalence of Bb-infection in I. scapularis has rapidly increased over three decades as reported by tick surveillance studies in Canada which coincides with increasing human incidence for LD. The wide-ranging distribution and variable prevalence of Bb-infected I. scapularis ticks across provinces demonstrates the growing need for long-term standardized tick surveillance to monitor the changing trends in I. scapularis populations and best define LD risk areas in Canada., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PHK, YT, QY, MS, AD, MM, AG, KH, FJA, JM and JHS are employees of Pfizer and may hold shares and/or stock options in the company. The other authors have no potential conflict of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Haploid induction (HI) holds great promise in expediting the breeding process in onion, a biennial cross-pollinated crop. We used the CENH3-based genome elimination technique in producing a HI line in onion. Here, we downregulated AcCENH3 using the RNAi approach without complementation in five independent lines. Out of five events, only three could produce seeds upon selfing. The progenies showed poor seed set and segregation distortion, and we were unable to recover homozygous knockdown lines. The knockdown lines showed a decrease in accumulation of AcCENH3 transcript and protein in leaf tissue. The decrease in protein content in transgenic plants was correlated with poor seed set. When the heterozygous knockdown lines were crossed with wild-type plants, progenies showed HI by genome elimination of the parental chromosomes from AcCENH3 knockdown lines. The HI efficiency observed was between 0 and 4.63% in the three events, and it was the highest (4.63%) when E1 line was crossed with wildtype. Given the importance of doubled haploids in breeding programmes, the findings from our study are poised to significantly impact onion breeding., (© 2024. The Author(s).)

Background: In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF., Methodology/principal Findings: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred., Conclusions/significance: Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia., Trial Registration: CTRI/2017/04/008421., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MdB declares consultancy fees from DNDi. The remaining authors report no conflicts of interest., (Copyright: © 2024 Sundar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although missed appointments in healthcare have been an area of concern for policy, practice and research, the primary focus has been on reducing single 'situational' missed appointments to the benefit of services. Little attention has been paid to the causes and consequences of more 'enduring' multiple missed appointments in primary care and the role this has in producing health inequalities., Methods: We conducted a realist review of the literature on multiple missed appointments to identify the causes of 'missingness.' We searched multiple databases, carried out iterative citation-tracking on key papers on the topic of missed appointments and identified papers through searches of grey literature. We synthesised evidence from 197 papers, drawing on the theoretical frameworks of candidacy and fundamental causation., Results: Missingness is caused by an overlapping set of complex factors, including patients not identifying a need for an appointment or feeling it is 'for them'; appointments as sites of poor communication, power imbalance and relational threat; patients being exposed to competing demands, priorities and urgencies; issues of travel and mobility; and an absence of choice or flexibility in when, where and with whom appointments take place., Conclusions: Interventions to address missingness at policy and practice levels should be theoretically informed, tailored to patients experiencing missingness and their identified needs and barriers; be cognisant of causal domains at multiple levels and address as many as practical; and be designed to increase safety for those seeking care., (© 2024. The Author(s).)

HER2-targeting therapies have advanced breast cancer treatment over the past decade. Clinically, eligibility for HER2 therapies is determined by assessing HER2 levels on tumor cell surfaces through immunohistochemistry or by gene regulation through fluorescence in situ hybridization. HER2 therapies are not always effective in patients with elevated levels of HER2, questioning whether the amount of HER2 is sufficiently predictive of patient outcomes. Additionally, the HER2-targeting antibody-drug conjugate (ADC) Enhertu ® was recently approved for metastasized HER2-low cancers, confirming the benefits of HER2 treatment for patients with low HER2 levels. To evaluate the correlation between HER2 levels and treatment efficacy, we quantified HER2 on eight cell lines using flow cytometry while simultaneously determining the toxicity of two HER2-targeting ADCs. Both HER2-high cell lines and HER2-low cell lines had significant toxicity responses to ADCs. We quantified HER2 internalization and found no correlation between HER2 levels and the percentage of internalization. We found a useful metric suggesting that a minimum number of HER2 receptors trafficked to lysosomes is sufficient to provide effective treatment. Our results indicate that the current standards of determining eligibility for HER2 therapy could limit patients' access to effective treatment. In conclusion, HER2 levels are not wholly adequate to determine the response to ADC treatment.

Background: Definitive surgical care is often delayed in hypertrophic pyloric stenosis (HPS). Our aim is to evaluate the effect modifiable factors in preoperative HPS management have on efficiency of care., Methods: A retrospective review of all patients undergoing pyloromyotomy for HPS at two US children's hospitals between 2008 and 2018 was performed., Results: 406 patients were included in the study. The majority (310, 76 ​%) were adequately resuscitated and ready for surgery upon diagnosis in the ER. However, only 133 patients (43 ​%) had surgery on the day of admission. Patients diagnosed between 12pm and 6pm were more likely to have surgery the next day than those diagnosed before noon (67 ​% vs 33 ​%, p ​< ​.001), which correlated with a longer length of stay (32 vs 47 ​h, p ​< ​.001)., Conclusion: The majority of patients presenting with HPS can safely undergo same day surgery. Delaying surgery due to an afternoon diagnosis is common, and leads to a modifiable increased total length of stay., Competing Interests: Declaration of competing interest All authors declare that they have no pertinent conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

In this study, we evaluated the immunogenicity and protective immunity of in vitro transcribed Venezuelan equine encephalitis virus (VEEV TC-83 strain) self-amplifying RNA (saRNA) encoding the SARS-CoV-2 spike (S) protein in wild type (S-WT) and stabilized pre-fusion conformations (S-PP). Immunization with S-WT and S-PP saRNA induced specific neutralizing antibody responses in both K18-Tg hACE2 (K18) and BALB/c mice, as assessed using SARS-CoV-2 pseudotyped viruses. Protective immunity was assessed in challenge experiments. Two immunizations with S-WT and S-PP induced protective immunity, evidenced by lower mortality, lower weight loss and more than one log10 lower subgenomic virus RNA titers in the upper and lower respiratory tracts in both K18 and BALB/c mice. Histopathologic examination of lungs post-challenge showed that immunization with S-WT and S-PP resulted in a higher degree of immune cell infiltration and inflammatory changes, compared with control mice, characterized by high levels of T- and B-cell infiltration. No substantial differences were found in the presence and localization of eosinophils, macrophages, neutrophils, and natural killer cells. CD4 and CD8 T-cell depletion post immunization resulted in reduced lung inflammation post challenge but also prolonged virus clearance. These data indicate that immunization with saRNA encoding the SARS-CoV-2 S protein induces immune responses that are protective following challenge, that virus clearance is associated with pulmonary changes caused by T-cell and B-cell infiltration in the lungs, but that this T and B-cell infiltration plays an important role in viral clearance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management., Competing Interests: The authors have no conflict of interest to declare., (Copyright: © 2023 Giridharan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor activates cytoprotective and metabolic gene expression in response to various electrophilic stressors. Constitutive NRF2 activity promotes cancer progression, whereas decreased NRF2 function contributes to neurodegenerative diseases. We used proximity proteomic analysis to define protein networks for NRF2 and its family members NRF1, NRF3, and the NRF2 heterodimer MAFG. A functional screen of co-complexed proteins revealed previously uncharacterized regulators of NRF2 transcriptional activity. We found that ZNF746 (also known as PARIS), a zinc finger transcription factor implicated in Parkinson's disease, physically associated with NRF2 and MAFG, resulting in suppression of NRF2-driven transcription. ZNF746 overexpression increased oxidative stress and apoptosis in a neuronal cell model of Parkinson's disease, phenotypes that were reversed by chemical and genetic hyperactivation of NRF2. This study presents a functionally annotated proximity network for NRF2 and suggests a link between ZNF746 overexpression in Parkinson's disease and inhibition of NRF2-driven neuroprotection.

Background: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection., Methods: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated., Results: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 -25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29-1.73), being male (aRR:1.26; 95%CI: 1.18-1.34), residing in urban location (aRR:1.58; 95%CI: 1.03-2.43) and past history of TB (aRR:1.49; 95%CI: 1.26-1.76)., Conclusion: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acyl-protein thioesterases 1 and 2 (APT1 and APT2) reverse S-acylation, a potential regulator of systemic glucose metabolism in mammals. Palmitoylation proteomics in liver-specific knockout mice shows that APT1 predominates over APT2, primarily depalmitoylating mitochondrial proteins, including proteins linked to glutamine metabolism. miniTurbo-facilitated determination of the protein-protein proximity network of APT1 and APT2 in HepG2 cells reveals APT proximity networks encompassing mitochondrial proteins including the major translocases Tomm20 and Timm44. APT1 also interacts with Slc1a5 (ASCT2), the only glutamine transporter known to localize to mitochondria. High-fat-diet-fed male mice with dual (but not single) hepatic deletion of APT1 and APT2 have insulin resistance, fasting hyperglycemia, increased glutamine-driven gluconeogenesis, and decreased liver mass. These data suggest that APT1 and APT2 regulation of hepatic glucose metabolism and insulin signaling is functionally redundant. Identification of substrates and protein-protein proximity networks for APT1 and APT2 establishes a framework for defining mechanisms underlying metabolic disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardiac rehabilitation (CR) can reduce mortality and improve physical functioning in older patients, but current programs do not support the needs of older patients with comorbidities or frailty, for example due to transport problems and physical limitations. Home-exercise-based cardiac rehabilitation (HEBCR) programs may better meet these needs, but physiotherapy guidelines for personalising HEBCR for older, frail patients with cardiovascular disease are lacking., Purpose: To provide expert recommendations for physiotherapists on how to administer HEBCR to older adults with comorbidities or frailty., Methods: This Delphi study involved a panel of Dutch experts in physiotherapy, exercise physiology, and cardiology. Three Delphi rounds were conducted between December 2020 and February 2022. In the first round panellists provided expertise on applicability and adaptability of existing CR-guidelines. In the second round panellists ranked the importance of statements about HEBCR for older adults. In the third round panellists re-ranked statements when individual scores were outside the semi-interquartile range. Consensus was defined as a semi-interquartile range of ≤ 1.0., Results: Of 20 invited panellists, 11 (55%) participated. Panellists were clinical experts with a median (interquartile range) work experience of 20 (10.5) years. The panel reached a consensus on 89% of statements, identifying key topics such as implementing the patient perspective, assessing comorbidity and frailty barriers to exercise, and focusing on personal goals and preferences., Conclusion: This Delphi study provides recommendations for personalised HEBCR for older, frail patients with cardiovascular disease, which can improve the effectiveness of CR-programs and address the needs of this patient population. Prioritising interventions aimed at enhancing balance, lower extremity strength, and daily activities over interventions targeting exercise capacity may contribute to a more holistic and effective approach, particularly for older adults., Competing Interests: The authors report there are no competing interests to declare., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2 high ESCC., Design: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays., Results: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as potential NRF2 inhibitors with minimal cytotoxicity at specified concentrations. We then validated two of these compounds, pyrimethamine and mitoxantrone, by demonstrating their dose- and time-dependent inhibitory effects on the expression of NRF2 and its target genes in two NRF2 Mut human ESCC cells (KYSE70 and KYSE180). RNAseq and qPCR confirmed the suppression of global NRF2 signaling by these two compounds. Mechanistically, pyrimethamine reduced NRF2 half-life by promoting NRF2 ubiquitination and degradation in KYSE70 and KYSE180 cells. Expression of an Nrf2 E79Q allele in mouse esophageal epithelium (Sox2CreER;LSL-Nrf2 E79Q/+ ) resulted in an NRF2 high phenotype, which included squamous hyperplasia, hyperkeratinization, and hyperactive glycolysis. Treatment with pyrimethamine (30 mg/kg/day, p.o.) suppressed the NRF2 high esophageal phenotype with no observed toxicity., Conclusion: We have identified and validated pyrimethamine as an NRF2 inhibitor that may be rapidly tested in the clinic for NRF2 high ESCC., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This work investigates the effect of copper substitution on the magnetic properties of SmCo 5 thin films synthesized by molecular beam epitaxy. A series of thin films with varying concentrations of Cu were grown under otherwise identical conditions to disentangle structural and compositional effects on the magnetic behavior. The combined experimental and theoretical studies show that Cu substitution at the Co 3g sites not only stabilizes the formation of the SmCo 5 structure but also enhances magnetic anisotropy and coercivity. Density functional theory calculations indicate that Sm(Co 4 Cu 3g ) 5 possesses a higher single-ion anisotropy as compared to pure SmCo 5 . In addition, X-ray magnetic circular dichroism reveals that Cu substitution causes an increasing decoupling of the Sm 4f and Co 3d moments. Scanning transmission electron microscopy confirms predominantly SmCo 5 phase formation and reveals nanoscale inhomogeneities in the Cu and Co distribution. Our study based on thin film model systems and advanced characterization as well as modeling reveals novel aspects of the complex interplay of intrinsic and extrinsic contributions to magnetic hysteresis in rare-earth-based magnets, i.e., the combination of increased intrinsic anisotropy due to Cu substitution and the extrinsic effect of inhomogeneous elemental distribution of Cu and Co.

(1) Background: Oxidative stress markers in the follicular fluid and serum of the patient with IVF results (number of fertilized oocytes, number of embryos, cumulative pregnancy rate) are important in establishing the causes of infertility. (2) Methods: 42 patients were enrolled in the study over the duration of 24 months and were divided into two groups: the study group divided into the female etiology for infertility as a tubal factor, diminished ovarian reserve, endometriosis, and unexplained infertility, and the control group consisting of the male factor, excluding the sperm donors and with no female factor cause. On the day of ovarian puncture in IVF, follicular fluid and serum were collected from the patients. (3) Results: Malondialdehyde from the follicular fluid was higher in the control group. The total antioxidant capacity in the follicular fluid is positively correlated with the pregnancy rate. There is no statistically significant difference in the oxidative stress markers from serum in both groups. (4) Conclusions: The capacity of the follicular fluid environment to contain the reactive oxygen species (ROS) leads to a higher pregnancy rate in the control group.

Introduction: Waterlogging is a major stress that severely affects onion cultivation worldwide, and developing stress-tolerant varieties could be a valuable measure for overcoming its adverse effects. Gathering information regarding the molecular mechanisms and gene expression patterns of waterlogging-tolerant and sensitive genotypes is an effective method for improving stress tolerance in onions. To date, the waterlogging tolerance-governing molecular mechanism in onions is unknown., Methods: This study identified the differentially expressed genes (DEGs) through transcriptome analysis in leaf tissue of two onion genotypes (Acc. 1666; tolerant and W-344; sensitive) presenting contrasting responses to waterlogging stress., Results: Differential gene expression analysis revealed that in Acc. 1666, 1629 and 3271 genes were upregulated and downregulated, respectively. In W-344, 2134 and 1909 genes were upregulated and downregulated, respectively, under waterlogging stress. The proteins coded by these DEGs regulate several key biological processes to overcome waterlogging stress such as phytohormone production, antioxidant enzymes, programmed cell death, and energy production. The clusters of orthologous group pathway analysis revealed that DEGs contributed to the post-translational modification, energy production, and carbohydrate metabolism-related pathways under waterlogging stress. The enzyme assay demonstrated higher activity of antioxidant enzymes in Acc. 1666 than in W-344. The differential expression of waterlogging tolerance related genes, such as those related to antioxidant enzymes, phytohormone biosynthesis, carbohydrate metabolism, and transcriptional factors, suggested that significant fine reprogramming of gene expression occurs in response to waterlogging stress in onion. A few genes such as ADH, PDC, PEP carboxylase, WRKY22, and Respiratory burst oxidase D were exclusively upregulated in Acc. 1666., Discussion: The molecular information about DEGs identified in the present study would be valuable for improving stress tolerance and for developing waterlogging tolerant onion varieties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gedam, Khandagale, Shirsat, Thangasamy, Kulkarni, Kulkarni, Patil, Barvkar, Mahajan, Gupta, Bhagat, Khade, Singh and Gawande.)

This paper discusses an innovative APS hollow block wall with a frame made of concrete modified with recycled materials. The technical data of the hollow block, the percentages of the recycled materials, including SBR rubber granules and PET flakes in the modified concrete, and the composition of the concrete modified with this mixture of recycled additives, are presented. To demonstrate the effectiveness of the solution in reducing mechanical vibrations, the effect of the interaction of different frequencies of the mechanical wave on reducing these vibrations was evaluated for APS blocks and Alpha comparison blocks. The test was carried out on a developed test stand dedicated to dynamic measurements for sixteen frequencies in the range from 8 to 5000 Hz, forcing a sinusoidal course of vibrations. The results are presented graphically and show that the new type of APS hollow block wall was much more effective in reducing mechanical vibrations. This efficiency was in the range from 10 to 51% for 12 out of the tested 16 frequencies. For the frequencies of 8, 16, 128, and 2000 Hz, the values were obtained with a difference of 3.58% in favor of the APS hollow block. In addition, the study of the damping effectiveness of the APS hollow blocks, in relation to the vibrations generated by an M-400 impact mill, showed that the APS block wall had a higher damping efficiency of 16.87% compared to the Alpha hollow block for the signal reading on the floor next to the mill, and 18.68% for the signal reading on the mill body. The modified concrete used in the production of the APS hollow blocks enabled the effective use of two recycled materials, SBR rubber and polyethylene terephthalate, in the form of PET flakes.

Objective: This study investigates the feasibility of delivering inspiratory muscle training as part of the physical therapy treatment for patients with post-COVID dyspnoea., Design: Mixed-methods pilot study., Subjects/patients: Patients with complaints of dyspnoea after COVID-19 infection and their physical therapists., Methods: The Amsterdam University of Applied Sciences and the Amsterdam University Medical Centers conducted this study. Participants performed daily inspiratory muscle training at home for 6 weeks, consisting of 30 repetitions against a pre-set resistance. The primary outcome was feasibility assessed as acceptability, safety, adherence and patient- and professional experience obtained through diaries and semi-structured interviews. The secondary outcome was maximal inspiratory pressure., Results: Sixteen patients participated. Nine patients and 2 physical therapists partook in semi-structured interviews. Two patients dropped out before initiating the training. Adherence was 73.7%, and no adverse events occurred. Protocol deviations occurred in 29.7% of the sessions. Maximal inspiratory pressure changed from 84.7% of predicted at baseline to 111.3% at follow-up. Qualitative analysis identified barriers to training: 'Getting acquainted with the training material' and 'Finding the right schedule'. Facilitators were: 'Support from physical therapists' and 'Experiencing improvements'., Conclusion: Delivering inspiratory muscle training to patients with post-COVID dyspnoea seems feasible. Patients valued the simplicity of the intervention and reported perceived improvements. However, the intervention should be carefully supervised, and training parameters adjusted to individual needs and capacity., Competing Interests: The authors have no conflicts of interest to declare., (© Published by Medical Journals Sweden, on behalf of the Foundation for Rehabilitation Information.)

Onion thrips, Thrips tabaci Lindeman, an economically important onion pest in India, poses a severe threat to the domestic and export supply of onions. Therefore, it is important to study the distribution of this pest in order to assess the possible crop loss, which it may inflict if not managed in time. In this study, MaxEnt was used to analyze the potential distribution of T. tabaci in India and predict the changes in the suitable areas for onion thrips under two scenarios, SSP126 and SSP585. The area under the receiver operating characteristic curve values of 0.993 and 0.989 for training and testing demonstrated excellent model accuracy. The true skill statistic value of 0.944 and 0.921, and the continuous Boyce index of 0.964 and 0.889 for training and testing, also showed higher model accuracy. Annual Mean Temperature (bio1), Annual Precipitation (bio12) and Precipitation Seasonality (bio15) are the main variables that determined the potential distribution of T. tabaci, with the suitable range of 22-28 °C; 300-1000 mm and 70-160, respectively. T. tabaci is distributed mainly in India's central and southern states, with 1.17 × 10 6  km 2 , covering 36.4% of land area under the current scenario. Multimodal ensembles show that under a low emission scenario (SSP126), low, moderate and optimum suitable areas of T. tabaci is likely to increase, while highly suitable areas would decrease by 17.4% in 2050 20.9% in 2070. Whereas, under the high emission scenario (SSP585), the high suitability is likely to contract by 24.2% and 51.7% for 2050 and 2070, respectively. According to the prediction of the BCC-CSM2-MR, CanESM5, CNRM-CM6-1 and MIROC6 model, the highly suitable area for T. tabaci would likely contract under both SSP126 and SSP585. This study detailed the potential future habitable area for T. tabaci in India, which could help monitor and devise efficient management strategies for this destructive pest., (© 2023. The Author(s).)

Background: Post-kala-azar dermal leishmaniasis (PKDL), a dermal form of the disease, occurs in some visceral leishmaniasis (VL) patients following treatment. The PKDL disease mechanism is not yet clearly understood. Here we have studied the role of dermal fibroblasts in VL and PKDL disease mechanism., Methods: Dermal fibroblasts were grown from skin biopsy explants collected from individual VL and PKDL patients and healthy controls. Fibroblasts from the third passage were subjected to RNA sequencing to analyze differentially expressed genes (DEGs). Significantly important genes were further validated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA)., Results: Transcriptome analysis of PKDL versus VL identified 516 DEGs (263 were overrepresented and 253 were underrepresented in PKDL). Among the top hub genes, MMP2, IL1B, CXCL8, IFIH1, NFKB1A, IL6, ISG15, and EGFR were underexpressed and ACTB, HSP90AA1, RAB7A, and RPS27A were overexpressed in PKDL compared to VL., Conclusions: Our data indicate that PKDL fibroblasts may present antigens through the MHC I pathway activating CD8+ T-cell mediated response, while VL fibroblasts express nuclear factor-κB (NFκB)-mediated chemokines, IL1B, IL6, and IL8, resulting in the recruitment of natural killer (NK)-cells and monocytes to the site of infection, leading to the clearance of parasite from the skin and visceralization of the disease., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Mechanical ventilation affects the respiratory muscles, but little is known about long-term recovery of respiratory muscle weakness (RMW) and potential associations with physical functioning in survivors of critical illness. The aim of this study was to investigate the course of recovery of RMW and its association with functional outcomes in patients who received mechanical ventilation., Methods: We conducted a prospective cohort study with 6-month follow-up among survivors of critical illness who received ≥ 48 hours of invasive mechanical ventilation. Primary outcomes, measured at 3 timepoints, were maximal inspiratory and expiratory pressures (MIP/MEP). Secondary outcomes were functional exercise capacity (FEC) and handgrip strength (HGS). Longitudinal changes in outcomes and potential associations between MIP/MEP, predictor variables, and secondary outcomes were investigated through linear mixed model analysis., Results: A total of 59 participants (male: 64%, median age [IQR]: 62 [53-66]) were included in this study with a median (IQR) ICU and hospital length of stay of 11 (8-21) and 35 (21-52) days respectively. While all measures were well below predicted values at hospital discharge (MIP: 68.4%, MEP 76.0%, HGS 73.3% of predicted and FEC 54.8 steps/2m), significant 6-month recovery was seen for all outcomes. Multivariate analyses showed longitudinal associations between older age and decreased MIP and FEC, and longer hospital length of stay and decreased MIP and HGS outcomes. In crude models, significant, longitudinal associations were found between MIP/MEP and FEC and HGS outcomes. While these associations remained in most adjusted models, an interaction effect was observed for sex., Conclusion: RMW was observed directly after hospital discharge while 6-month recovery to predicted values was noted for all outcomes. Longitudinal associations were found between MIP and MEP and more commonly used measures for physical functioning, highlighting the need for continued assessment of respiratory muscle strength in deconditioned patients who are discharged from ICU. The potential of targeted training extending beyond ICU and hospital discharge should be further explored., Competing Interests: The authors have declared that they have no competing interests, (Copyright: © 2023 Major et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi sarcoma (KS), the plasmablastic form of multicentric Castleman's disease, and primary effusion lymphoma. In sub-Saharan Africa, KS is the most common HIV-related malignancy and one of the most common childhood cancers. Immunosuppressed patients, including HIV-infected patients, are more prone to KSHV-associated disease. KSHV encodes a viral protein kinase (vPK) that is expressed from ORF36. KSHV vPK contributes to the optimal production of infectious viral progeny and upregulation of protein synthesis. To elucidate the interactions of vPK with cellular proteins in KSHV-infected cells, we used a bottom-up proteomics approach and identified host protein ubiquitin-specific peptidase 9X-linked (USP9X) as a potential interactor of vPK. Subsequently, we validated this interaction using a co-immunoprecipitation assay. We report that both the ubiquitin-like and the catalytic domains of USP9X are important for association with vPK. To uncover the biological relevance of the USP9X/vPK interaction, we investigated whether the knockdown of USP9X would modulate viral reactivation. Our data suggest that depletion of USP9X inhibits both viral reactivation and the production of infectious virions. Understanding how USP9X influences the reactivation of KSHV will provide insights into how cellular deubiquitinases regulate viral kinase activity and how viruses co-opt cellular deubiquitinases to propagate infection. Hence, characterizing the roles of USP9X and vPK during KSHV infection constitutes a first step toward identifying a potentially critical interaction that could be targeted by future therapeutics. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi sarcoma (KS), the plasmablastic form of multicentric Castleman's disease, and primary effusion lymphoma. In sub-Saharan Africa, KS is the most common HIV-related malignancy. KSHV encodes a viral protein kinase (vPK) that aids viral replication. To elucidate the interactions of vPK with cellular proteins in KSHV-infected cells, we used an affinity purification approach and identified host protein ubiquitin-specific peptidase 9X-linked (USP9X) as a potential interactor of vPK. Depletion of USP9X inhibits both viral reactivation and the production of infectious virions. Overall, our data suggest a proviral role for USP9X.

Since November 2021, Omicron has been the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that causes the coronavirus disease 2019 (COVID-19) and has continuously impacted human health. Omicron sublineages are still increasing and cause increased transmission and infection rates. The additional 15 mutations on the receptor binding domain (RBD) of Omicron spike proteins change the protein conformation, enabling the Omicron variant to evade neutralizing antibodies. For this reason, many efforts have been made to design new antigenic variants to induce effective antibodies in SARS-CoV-2 vaccine development. However, understanding the different states of Omicron spike proteins with and without external molecules has not yet been addressed. In this review, we analyze the structures of the spike protein in the presence and absence of angiotensin-converting enzyme 2 (ACE2) and antibodies. Compared to previously determined structures for the wildtype spike protein and other variants such as alpha, beta, delta, and gamma, the Omicron spike protein adopts a partially open form. The open-form spike protein with one RBD up is dominant, followed by the open-form spike protein with two RBD up, and the closed-form spike protein with the RBD down. It is suggested that the competition between antibodies and ACE2 induces interactions between adjacent RBDs of the spike protein, which lead to a partially open form of the Omicron spike protein. The comprehensive structural information of Omicron spike proteins could be helpful for the efficient design of vaccines against the Omicron variant.

Purpose: The Coronavirus disease 2019 pandemic occurred during the interview period for numerous surgical fellowships, resulting in most programs transitioning to a virtual interview format during the 2020-2021 application cycle. This study investigated modifications adopted by fellowship programs and perceptions of the virtual interview format among hand surgery fellowship applicants., Methods: Voluntary, anonymous online surveys were emailed to all applicants to the Johns Hopkins hand surgery fellowship during the 2020-2021 interview cycle. The surveys were released after the rank order list certification deadline on May 6, 2021, and closed on May 18, 2021, before the match results were released. Descriptive statistics based on the overall cohort and primary outcome of an applicant's willingness to recommend virtual interviews in the future were conducted., Results: Thirty-four of 112 (30.4%) applicants completed their surveys. Twenty-seven (79.4%) survey respondents recommended the virtual interview format in the future and 7 (20.6%) did not. Applicants who recommended virtual interviews were similar to those who did not on the basis of the number of interviews received and taken, information provided by programs, and self-rated competency with the virtual interview format. Those who recommended virtual interviews rated the effectiveness of self-advocacy higher compared with those who did not. All respondents agreed that cost savings and scheduling were more effective with virtual interviews. Perceived weaknesses differed between the 2 groups and included the lack of physical tour, difficulty with self-advocacy, and technical difficulties. The majority of survey respondents preferred in-person interviews before the interview cycle (n = 32, 94.1%), whereas nearly half of survey respondents preferred virtual interviews after the interview cycle (n = 16, 47.1%)., Conclusions: Nearly 80% of survey respondents recommended virtual interviews in the future. Major benefits included effectiveness of scheduling and cost savings., Clinical Relevance: Virtual interviews may be considered as an alternative or adjunct to in-person hand surgery fellowship interviews in the future., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: A hepatitis B vaccination (HepB) series with an initial dose of hepatitis B immune globulin (HBIG) is the recommended prophylaxis for infants born to mothers with chronic hepatitis B virus (HBV) infection and for HBV-exposed persons without known protection. The HepB and HBIG are administered at different sites (limbs). Instances of HepB and HBIG administered at the same site are documented but the impact on immune responses to HepB remains unanswered., Methods: Newborn and adult BALB/c mice received one dose of HepB at time zero alone or with HBIG in the same or different sites, followed by 2 additional doses of HepB at 3 and 10 weeks (newborn mice) or 4 and 16 weeks (adult mice). To study memory responses mice were given a 4th, booster, dose of HepB at 26 weeks and B cells analyzed., Results: Administration of HepB with HBIG resulted in reduced responses to HepB following the first 2 doses, regardless of site, compared to mice that received HepB only. Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series (p < 0.0001) in all groups of newborn mice that received HepB and HBIG. In adult mice, this difference was only seen when HepB and HBIG were delivered at the same site. However, following a HepB booster at 26 weeks, HBsAg-specific B-cell expansion and memory phenotype were not impacted by initial HBIG administration CONCLUSION: Administration of HBIG with HepB can delay and reduce responses to HepB in mice. Our findings suggest that the initial circulating levels of HBIG could prevent infection despite an impaired response to vaccine and support the current recommendation of assessing seroprotection after series completion for infants born to HBV carrier mothers, including in cases where vaccine and HBIG are administered incorrectly at the same site., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Garlic ( Allium sativum L.) is a clonally propagated bulbous crop and can be infected by several viruses under field conditions. A virus complex reduces garlic yield and deteriorates the quality of the produce. In the present study, we aimed to eliminate Onion yellow dwarf virus (OYDV), Garlic common latent virus (GCLV), Shallot latent virus (SLV), and Allexiviruses from the infected crop using combination of meristem culture, thermotherapy, and chemotherapy. In this study, seven different treatments, namely shoot meristem culture, thermotherapy direct culture, chemotherapy direct culture, chemotherapy + meristem culture, thermotherapy + meristem culture, thermotherapy + chemotherapy direct culture, and thermotherapy + chemotherapy + meristem culture (TCMC), were used. Multiplex polymerase chain reaction (PCR) was employed to detect virus elimination, which revealed the percentage of virus-free plants was between 65 and 100%, 55 and 100%, and 13 and 100% in the case of GCLV, SLV, and OYDV, respectively. The in vitro regeneration efficiency was between 66.06 and 98.98%. However, the elimination of Allexiviruses could not be achieved. TCMC was the most effective treatment for eliminating GCLV, SLV, and OYDV from garlic, with 66.06% plant regeneration efficiency. The viral titre of the Allexivirus under all the treatments was monitored using real-time PCR, and the lowest viral load was observed in the TCMC treatment. The present study is the first to report the complete removal of GCLV, SLV, and OYDV from Indian red garlic with the application of thermotherapy coupled with chemotherapy and shoot meristem culture.

In order to examine the effects of vaccine type and timing of crossbred beef calves ( n = 151) were assigned to one of three BRD vaccination protocols stratified by breed of sire, sex, and date of birth, which included: (1) KM-a pentavalent killed viral (KV) vaccine at 2 to 3 months of age (D 0) and a pentavalent modified-live viral (MLV) vaccine at weaning (D 127); (2) MM-MLV on D 0 and revaccinated on D 127 or (3) WN-MLV at weaning and D 140. Vaccination treatment did not affect performance nor BRSV serum-neutralizing antibody titers. Serum-neutralizing antibody titers to BVDV-1 were greatest for the MM through D 154. However, following booster (KM) or initial vaccination (WN) at D 127, titers increased for the other treatment groups to higher values (KM) by the end of the study. Delay of initial vaccination until weaning may have delayed specific antibody response in the WN group and skewed the immune response towards a Th-1 or cell-mediated response. Overall, the inclusion of an MLV in the vaccine protocol resulted in a more robust antibody response, and the timing of vaccination may affect the onset of efficacious and robust vaccine responses.

Objective: We aim to survey and compare integrated plastic surgery and plastic surgery subspecialty fellowship applicants on their experiences with virtual interviews and to determine if there are differences between them., Design: An IRB-approved survey study was conducted using the Qualtrics platform., Setting: The study was conducted at the Johns Hopkins University and the R Adams Cowley Shock Trauma Center in Baltimore Maryland., Participants: Applicants that applied to 1) the Johns Hopkins/University of Maryland or the University of California San Diego integrated plastic surgery residency programs, 2) craniofacial surgery fellowship, and 3) microsurgery, hand surgery, or burn surgery fellowship at the Johns Hopkins University were selected to participate in the survey., Results: A total of 94 surveys were completed by residency applicants and 55 by fellowship applicants. After the interview season, 80% of fellowship applicants recommended virtual interviews compared to 61.7% of residency applicants (p = 0.03). Fellowship applicants reported significantly less issues with self-advocacy and did not view the virtual interview process as significant of a detriment when meeting program residents/staff, viewing the hospital/surrounding area, and learning about the program (p < 0.05). A higher percentage of fellowship applicants interviewed at multiple programs during a single day compared to residency applicants (56.4% vs 27.7%; p < 0.001)., Conclusions: A higher proportion of fellowship applicants prefer virtual interviews, which associated with key differences in perceptions, expectations, and priorities. Our data supports that fellowship programs may wish to continue virtual interviews even after COVID-related restrictions are lifted, because fellows are equally able to self-advocate in a virtual format while benefiting from cost and time savings; fellowship programs would also gain the cost and time savings from this model as well., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Metabolic engineering of microorganisms aims to design strains capable of producing valuable compounds under relevant industrial conditions and in an economically competitive manner. From this perspective, and beyond the need for a catalyst, biomass is essentially a cost-intensive, abundant by-product of a microbial conversion. Yet, few broadly applicable strategies focus on the optimal balance between product and biomass formation. Here, we present a genetic control module that can be used to precisely modulate growth of the industrial bacterial chassis Pseudomonas putida KT2440. The strategy is based on the controllable expression of the key metabolic enzyme complex pyruvate dehydrogenase (PDH) which functions as a metabolic valve. By tuning the PDH activity, we accurately controlled biomass formation, resulting in six distinct growth rates with parallel overproduction of excess pyruvate. We deployed this strategy to identify optimal growth patterns that improved the production yield of 2-ketoisovalerate and lycopene by 2.5- and 1.38-fold, respectively. This ability to dynamically steer fluxes to balance growth and production substantially enhances the potential of this remarkable microbial chassis for a wide range of industrial applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

A new high radial resolution 2D multichannel Charge eXchange Imaging (CXI) diagnostic is under development for deployment at DIII-D. The diagnostic system will measure low-to-intermediate radial wavenumber carbon density fluctuations by observing the n = 8 - 7 (λ = 529.06 nm) C-VI emission line, resulting from charge exchange collisions between heating neutral beam atoms and the intrinsic carbon ion density. The new CXI diagnostic will provide measurements with ΔR ∼ 0.4 cm to access higher k r instabilities (k r < 8 cm -1 ) predicted to arise in the steep-gradient region of the H-mode pedestal. The CXI system will feature 60 fiber bundles in a 12 × 5 arrangement, with each bundle consisting of four 1 mm fibers. A custom optical system has been designed to filter and image incoming signals onto an 8 × 8 avalanche photodiode array. Additionally, a novel electronics suite has been designed and commissioned to amplify and digitize the relatively low-intensity carbon signal at a 2 MHz bandwidth. Forward modeling results of the active C-VI emission suggest sufficient signal to noise ratios to resolve turbulent fluctuations. Prototype measurements demonstrate the ability to perform high frequency pedestal measurements.

Introduction: The 2021 interview cycle for craniofacial fellowship applicants was the first to be held virtually due to the coronavirus disease 2019 pandemic. Here, we detail the craniofacial fellowship applicant perceptions and experience on the virtual interview process., Materials and Methods: An institutional review board-approved 35-question survey study on the perception of the virtual interview process among craniofacial fellowship applicants was conducted. Surveys were distributed to individuals who had applied through the match, overseen by the American Society of Craniofacial Surgeons (ASCFS)., Results: Ten surveys were fully completed with a corresponding response rate of 48%. The average number of interviews completed was 12.7±7.7 and 50% of applicants interviewed at >1 program in a single day. Overall, 90% of respondents preferred in-person interviews before the interview season, however, only 10% preferred the in-person format afterwards. Preference for a virtual-only format increased from 10% to 70%. Applicants cited cost (100%), ease of scheduling (90%), and ability to participate in more interviews (70%) as the primary strengths of the virtual platform; none reported difficulties with self-advocacy. After the interview cycle, 90% stated they would recommend virtual interviews., Conclusions: The greatest strengths of virtual interviews were the ability to participate in more interviews, the ease of scheduling, and the cost benefits. Most applicants reported the same or increased ability for self-advocacy with virtual interviews. Following the index interview cycle for 2021, the majority of fellowship applicants now appear to prefer a virtual-only or hybrid format and would recommend virtual interviews in the future., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Strategies for the most effective treatment for peripheral arterial disease (PAD) remain controversial among clinicians. Several trials have shown improved primary patency of femoropopliteal interventions with the utilization of paclitaxel-coated balloons or stents compared to conventional balloons or stents. However, a 2018 meta-analysis suggested an increased mortality risk for patients receiving drug-coated balloons or stents (DCBS), resulting in an international pause in the use of DCBS. A 2021 meta-analysis by the same group suggested an increased risk of major amputation following DCBS use in peripheral arterial revascularization procedures. Here we report our long-term institutional outcomes comparing uncoated devices to DCBS., Methods: A retrospective review of all patients who underwent peripheral arterial angioplasty, stenting, atherectomy, or a combination between 2011 and 2020 within a regional healthcare system was performed. Univariate, multivariate, and survival analyses were performed using standard statistical methods to assess the primary end points of overall survival, 5-year survival, and amputation-free survival., Results: A total of 2,717 patients were identified, of whom 1,965 were treated with conventional uncoated devices and 752 were treated with DCBS. A univariate analysis showed that patients treated with non-DCBS had higher rates of overall mortality, major amputations, and mortality at 1, 3, and 5 years. A multivariable analysis demonstrated that the use of conventional devices, age, diabetes, chronic kidney disease, myocardial infarction, transient ischemic attack, warfarin use, and atrial fibrillation all significantly increased the risk of 5-year mortality, overall mortality, and combined mortality and/or amputation., Conclusions: DCBS are not associated with increased mortality or worse amputation-free survival in this real-world cohort of patients treated for PAD. Our data suggest that mortality is more closely linked with pre-existing patient comorbidities rather than device selection at the time of revascularization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tomato production is severely affected by abiotic stresses (drought, flood, heat, and salt) and causes approximately 70% loss in yield depending on severity and duration of the stress. Drought is the most destructive abiotic stress and tomato is very sensitive to the drought stress, as cultivated tomato lack novel gene(s) for drought stress tolerance. Only 20% of agricultural land worldwide is irrigated, and only 14.51% of that is well-irrigated, while the rest is rain fed. This scenario makes drought very frequent, which restricts the genetically predetermined yield. Primarily, drought disturbs tomato plant physiology by altering plant-water relation and reactive oxygen species (ROS) generation. Many wild tomato species have drought tolerance gene(s); however, their exploitation is very difficult because of high genetic distance and pre- and post-transcriptional barriers for embryo development. To overcome these issues, biotechnological methods, including transgenic technology and CRISPR-Cas, are used to enhance drought tolerance in tomato. Transgenic technology permitted the exploitation of non-host gene/s. On the other hand, CRISPR-Cas9 technology facilitated the editing of host tomato gene(s) for drought stress tolerance. The present review provides updated information on biotechnological intervention in tomato for drought stress management and sustainable agriculture.

Purpose: This study investigates patients' experiences of interaction with their healthcare professionals (HCPs) during cancer treatment and identifies elements that HCPs can utilize to improve cancer care provision., Methods: PubMed, CINAHL, PsycINFO, SCOPUS, and Embase were systematically searched for relevant studies published from January 2010 until February 2022. Qualitative studies investigating adult patients' perspectives on their interaction with HCPs during cancer treatment were included. Studies conducted during the diagnosis or end-of-life treatment phase were excluded. Duplicate removal, screening, and quality appraisal were independently performed by four reviewers using Covidence.org. We performed a thematic meta-synthesis of qualitative data extracted from studies meeting the quality criteria in three stages: excerpts coding, codes categorization, and theme identification by merging similar categories., Results: Eighty-eight studies were included for quality appraisal, of which 50 papers met the quality inclusion criteria. Three themes were identified as essential to positively perceived patient-HCP interaction: "Support, respect and agency", "Quantity, timing, and clarity of information", and "Confidence, honesty, and expertise". Overall, patients experienced positive interaction with HCPs when the approach was person-centered and when HCPs possessed strong interpersonal skills. However, patients expressed negative experiences when their preferences regarding communication and the type of personal support needed were ignored., Conclusions: This meta-synthesis emphasizes the importance for HCPs to recognize all patients' needs, including communication and personal support preferences, to provide high-quality care. Consequently, healthcare professionals should continuously train their verbal and non-verbal communication, empathy, active listening, and collaboration skills during their undergraduate and continuing education., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aimed at understanding animal research technicians (ART) work activity to identify difficulties encountered by workers and their determinants which may increase musculoskeletal disorders (MSD) risks. The methods for the work activity analysis combined interviews, observations, events and operations chronicles as well as inclinometry. From the work activity analysis of the three main tasks (changing mouse cages, preparation of water bottles and unloading dirty material), difficulties such as awkward postures, heavy load handling, repetitiveness, high workload, supplementary tasks, interruptions and difficult social interactions emerged. The work activity analysis further allowed the identification of determinants of these difficulties. Some are related to the physical, organizational or social work environment, and others to the interdependence between these determinants. Such an improved understanding of ART work activity will lead to solutions best suited for MSDs prevention in this understudied setting., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To estimate the proportion of the population infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Canada through April 2021, 16 months into the coronavirus disease 2019 (COVID-19) pandemic and 4 months after COVID-19 vaccines became available., Methods: Publication databases, preprint servers, public health databases and the grey literature were searched for seroprevalence surveys conducted in Canada from 1 November 2019 to 10 July 2021. Studies were assessed for bias using the Joanna Briggs Checklist. Numbers of infections derived from seroprevalence estimates were compared with reported cases to estimate under-ascertainment ratios., Results: In total, 12 serosurveys with 210,321 participants were identified. Three (25%) serosurveys were conducted at national level, one (8.3%) was conducted at provincial level, and eight (66.7%) were conducted at local level. All 12 serosurveys had moderate or high risk of bias. The proportion of the population infected by April 2021 was low (2.6%). The proportion of the population infected was higher in surveys of residents of long-term care facilities (43.0-86%), workers at long-term care facilities (22.4-32.4%), and workers in healthcare institutions (1.4-14%)., Conclusions: As of April 2021, the proportion of the population infected by SARS-CoV-2 was low in the overall population of Canada, but was high in healthcare facilities, particularly long-term care facilities, supporting the need for vaccines., (© 2022 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.)

Onion is the most important crop challenged by a diverse group of insect pests in the agricultural ecosystem. The green semilooper (Chrysodeixis acuta Walker), a widespread tomato and soybean pest, has lately been described as an emergent onion crop pest in India. C. acuta whole mitochondrial genome was sequenced in this work. The circular genome of C. acuta measured 15,743 base pairs (bp) in length. Thirteen protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and one control region were found in the 37 sequence elements. With an average 395 bp gene length, the maximum and minimum gene length observed was 1749 bp and 63 bp of nad5 and trnR, respectively. Nine of the thirteen PCGs have (ATN) as a stop codon, while the other four have a single (T) as a stop codon. Except for trnS1, all of the tRNAs were capable of producing a conventional clover leaf structure. Conserved ATAGA motif sequences and poly-T stretch were identified at the start of the control region. Six overlapping areas and 18 intergenic spacer regions were found, with sizes ranged from 1 to 20 bp and 1 to 111 bp correspondingly. Phylogenetically, C. acuta belongs to the Plusiinae subfamily of the Noctuidae superfamily, and is closely linked to Trichoplusia ni species from the same subfamily. In the present study, the emerging onion pest C. acuta has its complete mitochondrial genome sequenced for the first time., Competing Interests: All the authors declare that there is no competing conflict of interest.

Cholera disproportionately affects the most vulnerable segments of the population, particularly those who have low or no access to basic water, sanitation, and hygiene (WASH). Despite some improvements in WASH conditions, cholera still represents a persistent challenge in Mozambique, where outbreaks occur almost every year, with high case fatality rates, posing a threat to the country's economic development. The Government of Mozambique has started developing a revised National Cholera Plan (NCP), which aligns with "ending cholera-a global roadmap to 2030" launched by the Global Task Force on Cholera Control (GTFCC) in 2017. Ending cholera represents a critical step towards achieving the sustainable development goals and requires effective prevention and control interventions, ensuring that no one is left behind. The NCP must use a multi-sector approach and broad stakeholder collaboration with well-coordinated roles and functions of different partners to address major areas for cholera elimination - water and sanitation, health care services and management, epidemiology and surveillance, and health and hygiene promotion. Every cholera death is preventable. In this review, we reiterate the need for effective coordinated actions to control and eliminate cholera in Mozambique and decrease the cholera burden, enabling a healthy population over the generations., Competing Interests: The authors declare no competing interest., (Copyright: Cynthia Semá Baltazar et al.)

The onion ( Allium cepa L.) is a lucrative and high-value vegetable-spice crop in India, but it is sensitive to several of diseases caused by fungi, bacteria, viruses, and nematodes, of which a fungal disease, anthracnose, caused by Colletotrichum spp., is a major issue for both onion producers and researchers since it severely affects the bulb production. Twister disease is currently one of the most common problems in onion production, particularly in humid regions, and it reduces productivity while also lowering the value and profitability. Twister disease is visualised by white or pale-yellow water-soaked oval depressed lesions on leaf blades, which are the first symptoms. Lesions expand as the disease advances, and numerous black-coloured, slightly elevated structures/fruiting bodies appear in the middle area, arranged in concentric rings. Curling, twisting, chlorosis of the leaves, and aberrant extension of the neck or pseudo-stem occurs, followed by rotting of the bulb. In an unmanaged crop, an excess gibberellin production by Colletotrichum gloeosporioides and Gibberella moniliformis is suspected to induce twisting and aberrant neck elongation, which will ruin onion productivity. It is difficult and environmentally unfriendly to control these infections. Since, to the best of our knowledge, this is the first review on onion anthracnose, we tried to consolidate information. This review updates our knowledge of the pathogen, including the disease cycle, infection pathways, and disease management techniques. As a result, growers will be benefit from the application of cultural, biological, and chemical measures and the use of resistant varieties.