bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the response of yellow lupine (Lupinus luteus L.) root to drought mediated by pathways related to phytohormones, lipid, and redox homeostasis
Authors: Burchardt Sebastian , Czernicka Małgorzata , Kućko Agata , Pokora Wojciech , Kapusta Małgorzata , Domagalski Krzysztof , Jasieniecka-Gazarkiewicz Katarzyna , Karwaszewski Jacek , Wilmowicz Emilia
Published: November 2024

Background

Yellow lupine (Lupinus luteus L.) is a high-protein crop of considerable economic and ecological significance. It has the ability to fix atmospheric nitrogen in symbiosis with Rhizobium, enriching marginal soils with this essential nutrient and reducing the need for artificial fertilizers. Additionally, lupine produces seeds with a high protein content, making it valuable for animal feed production. However, drought negatively affects lupine development, its mutualistic relationship with bacteria, and overall yield. To understand how lupine responds to this stress, global transcriptome sequencing was conducted, along with in-depth biochemical, chromatography, and microscopy analyses of roots subjected to drought. The results presented here contribute to strategies aimed at mitigating the effects of water deficit on lupine growth and development.

Results

Based on RNA-seq, drought-specific genes were identified and annotated to biological pathways involved in phytohormone biosynthesis/signaling, lipid metabolism, and redox homeostasis. Our findings indicate that drought-induced disruption of redox balance characterized by the upregulation of reactive oxygen species (ROS) scavenging enzymes, coincided with the accumulation of lipid-metabolizing enzymes, such as phospholipase D (PLD) and lipoxygenase (LOX). This disruption also led to modifications in lipid homeostasis, including increased levels of triacylglycerols (TAG) and free fatty acids (FFA), along with a decrease in polar lipid content. Additionally, the stress response involved alterations in the transcriptional regulation of the linolenic acid metabolism network, resulting in changes in the composition of fatty acids containing 18 carbons.

Conclusion

The first comprehensive global transcriptomic profiles of lupine roots, combined with the identification of key stress-responsive molecules, represent a significant advancement in understanding lupine’s responses to abiotic stress. The increased expression of the Δ12DESATURASE gene and enhanced PLD activity lead to higher level of linoleic acid (18:2), which is subsequently oxidized by LOX, resulting in membrane damage and malondialdehyde (MDA) accumulation. Oxidative stress elevates the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), while the conversion of FFAs into TAGs provides protection against ROS. This research offers valuable molecular and biochemical candidates with significant potential to enhance drought tolerance . It enables innovative strategies in lupine breeding and crop improvement to address critical agricultural challenges.
Perspectives of midwives on respectful maternity care
Authors: Lunda Petronella , Minnie Catharina Susanna , Lubbe Welma
Published: November 2024

Background

Respectful maternity care forms the foundation of maternity services; however, delivery of dignified, efficient, and effective care in these settings remains inconsistent. Research has identified several factors that influence respectful maternity care. To understand the South African context, these factors were explored and described from the perspectives of midwives. 

Methods

A qualitative descriptive inquiry was conducted, with participants recruited through snowball sampling on the social networking site Facebook. Semi-structured questions were used to collect data, to which participants responded in writing, detailing factors that influenced respectful care, including words and practices they associated with respectful maternity care. The data was analyzed using content analysis to identify common categories.

Results

Twenty-five responses from participants were analyzed; four categories and six sub-categories emerged as representations of respectful maternity care. The categories and sub-categories were as follows: healthcare professional behavior (ethical conduct and professional attributes related to education and training), managerial support (conducive work environment), interpersonal facet of care (characteristics of healthcare providers), and the birth environment (caring within the birth environment and client-centered care).

Conclusion

Midwives emphasized the importance of understanding respectful maternity care to ensure optimal outcomes for women, families, and communities. However, given the complexity of maternity care, it is crucial for policymakers, administrators, and midwives to comprehend and appreciate the various elements that define respectful care, as this understanding can significantly enhance its successful implementation.
A study of the enablers and barriers to the collection of sociodemographic data by public health units in Ontario, Canada during the COVID-19 pandemic
Authors: Komeiha Menna , Kujbida Gregory , Reynolds Aideen , Mbagwu Ikenna , Dojeiji Laurie , O’Rourke Joseph J. , Raju Shilpa , Varia Monali , Stylianou Helen , Burgess Sydnee , Ogundele Oluwasegun Jko , Pinto Andrew D.
Published: November 2024

Background

Collection and use of sociodemographic data (SDD), including race, ethnicity and income, are foundational to understanding health inequities. Ontario’s public health units collected SDD as part of COVID-19 case management and vaccination activities. This research aimed to identify enablers and barriers to collecting SDD during COVID-19 case management and vaccination.

Methods

As part of a larger mixed-method research study [1], qualitative methods were used to identify enablers and barriers to SDD collection during the COVID-19 pandemic. Purposive sampling was used to recruit participants from Ontario’s 34 public health units. Sixteen focus groups and eight interviews were conducted virtually using Zoom. Interview data were transcribed and analyzed using inductive and deductive qualitative description.

Results

SDD collection enablers included: legally mandating SDD collection and having dedicated data systems, technological and legal supports, senior management championing SDD collection, establishing rapport and trust between staff and clients, and gaining insight from the experiences from local communities and other jurisdictions. Identified barriers to SDD collection included: provincial data systems being perceived as lacking user-friendliness, SDD collection “was not a priority,” time and other constraints on building staff and client rapport, and perceived discomfort with asking and answering personal SDD questions.

Conclusion

A combination of provincial and local organizational strategies including supportive data systems, training, and frameworks for data collection and use, are needed to normalize and scale up SDD collection by local health units beyond the context of the COVID-19 pandemic.
Diagnosis and treatment of patients with gastroesophageal reflux disease – a systematic review of cost-effectiveness and economic burden
Authors: Maresova Petra , Rezny Lukas , Hruska Jan , Klimova Blanka , Swanstrom Lee L , Kuca Kamil
Published: November 2024

Background

This study aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages.

Methods

The study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included.

Results

Regarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies.

Discussion

The new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms.

Other

Advances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients’ quality of life.
Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial
Authors: Connon Roisin , Olupot-Olupot Peter , Pistorius Arthur M. A. , Okiror William , Ssenyondo Tonny , Muhindo Rita , Uyoga Sophie , Mpoya Ayub , Williams Thomas N. , Gibb Diana M. , Walker A. Sarah , ter Heine Rob , George Elizabeth C. , Maitland Kathryn
Published: November 2024

Background

African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.

Methods

We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled.

Results

Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls.

Conclusions

We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection.

Trial registration

ISRCTN49726849 (registered on 27th October 2017).
Descriptive embryological insights of the colorectum of quail embryos with concern to its functional morphology
Authors: Abdelhakeem Fatma , Madkour Fatma A.
Published: November 2024

Background

Quail is an interesting emerging bird species gaining attention in developmental embryology research due to its small size, quick lifespan, and fast growth rate. These characteristics make quail an ideal model for examining the development of the gastrointestinal tract. Consequently, the embryonic development of the colorectum was conducted to provide a comprehensive understanding of its functions in digestion, absorption, and immunity.

Methodology

The morphological anatomy and microscopical structure of the colorectal wall of 74 embryos were studied using light and scanning electron microscopy (SEM). Histologically, the embryos were collected and dissected to extract the intestine. The samples were then fixed in 10% neutral buffer formalin for a minimum of 24 h, and in 2.5% glutaraldehyde buffer formalin for semithin processing and scanning electron microscopy.

Results

The wall of the embryonic colorectum on the hatching day consisted of three layers; mucosa, muscularis externa, and serosa. Mucosa was a simple layer of columnar enterocytes interspersed with goblet cells that appeared as cub-like shaped cells. Additionally, two ganglionic plexuses were also developed in the colorectal wall; Auerbach plexus (among the colorectal tunica muscularis) and Meissner plexus (submucosal plexus).

Conclusion

The morphological characteristics of the quail colorectum at different ages were closely related to its functional features.
Somatic cell count in dairy goats I: association with infectious and non-infectious factors
Authors: Smistad Marit , Inglingstad Ragnhild Aabøe , Sølverød Liv , Skeie Siv , Hansen Bjørn Gunnar
Published: November 2024

Background

Intramammary infections negatively affect milk quality, animal welfare and productivity in the dairy industry. Somatic cell count (SCC) is the most used screening tool to detect subclinical mastitis caused by intramammary infections. In dairy goats, SCC is greatly influenced by non-infectious factors, which complicates the interpretation. The aim of this research paper was to determine the association between SCC, intramammary infections and non-infectious factors including parity, season, lactation stage, and milk yield in dairy goats. In this longitudinal study, 451 goats from four Norwegian dairy goat herds were sampled for bacteriology and SCC up to nine times during two lactations. Factors like parity, milk yield, and stage of lactation were retrieved from the Norwegian goat recording system.

Results

The most prevalent udder pathogen findings were Staphylococcus caprae (6.8%), Staphylococcus warneri (6.3%), and Staphylococcus epidermidis (3.8%), all of which had a mild but significant impact on SCC. Staphylococcus aureus was detected in 3.6% of the udder halves and had a major effect on SCC. Parity, stage of lactation, season, and milk yield significantly influenced SCC.

Conclusions

This study highlights that intramammary infections caused by Staphylococcus aureus, along with factors such as increasing parity and the seasonal effects of pasturing, significantly influence the SCC. Understanding these key contributors is essential for improving udder health management and improving milk quality in goat milk production.
Dynamics of cell-free tumor DNA correlate with early MRI response during chemoradiotherapy in rectal cancer
Authors: Clasen Kerstin , Gani Cihan , Schuetz Leon , Clasen Stephan , Ballin Nadja , Bonzheim Irina , Orth Michael , Ossowski Stephan , Riess Olaf , Niyazi Maximilian , Schroeder Christopher , Kelemen Olga
Published: November 2024

Background

In locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification.

Methods

In 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters.

Results

Most patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5.

Conclusions

Weekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found.
Treatment of acute pharyngitis in children: an Italian intersociety consensus (SIPPS-SIP-SITIP-FIMP-SIAIP-SIMRI-FIMMG)
Authors: Chiappini Elena , Simeone Giovanni , Bergamini Marcello , Pellegrino Roberta , Guarino Alfredo , Staiano Annamaria , Esposito Susanna , Gattinara Guido Castelli , Lo Vecchio Andrea , Stefani Stefania , Iacono Iride Dello , Scotese Immacolata , Tezza Giovanna , Dinardo Giulio , Riccio Simona , Pellizzari Sofia , Iavarone Sonia , Lorenzetti Giulia , Venturini Elisabetta , Donà Daniele , Pierantoni Luca , Doria Mattia , Garazzino Silvia , Midulla Fabio , Cricelli Claudio , Terracciano Luigi , Capuano Annalisa , Bruzzese Eugenia , Ghiglioni Daniele , Fusani Lara , Fusco Eleonora , Biasci Paolo , Reggiani Lamberto , Matera Luigi , Mancino Enrica , Barbieri Elisa , D’Avino Antonio , Cursi Laura , Sullo Maria Giuseppa , Scotti Silvestro , Marseglia Gian Luigi , Di Mauro Giuseppe , Principi Nicola , Galli Luisa , Verga Maria Carmen
Published: November 2024

Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50 mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery.
First case of infant botulism in Sicily—case report
Authors: Fazzino Antonino , Cavallaro Carmelinda , Cavataio Francesca , Linares Giulia , Lo Cascio Antonina , Lo Porto Carla , Santangelo Giuseppe , Venuti Laura , Corsello Giovanni , Colomba Claudia
Published: November 2024

Background

Botulism is a rare and life-threatening disease caused by the potent botulinum neurotoxin (BoNT), which can be produced by Clostridium botulinum (C. botulinum) and related bacteria. Clinical manifestations, which include a symmetrical, descending muscular paralysis, generalized hypotonia, and potentially respiratory failure, are non-specific and diagnosis is challenging, especially when anamnesis does not reveal any typical risk factor, like honey consumption.

Case Presentation

We present what is, to the best of our knowledge, the first documented case of infant botulism (IB) in Sicily and discuss its peculiarities and the challenges faced in the diagnostic-therapeutic process. The infant was exclusively breastfed and no history of consumption of possibly contaminated foods, like honey, was found. The signs observed at presentation included poor suction, hypotonia, and hyporeactivity. A detailed anamnesis motivated the suspicion of botulism, due to the occurrence of constipation and exposure to dust from home renovation works during the days before the onset of symptoms. The botulinum antitoxin was administered and the diagnosis was confirmed through fecal examination, detecting toxin-producing C. botulinum.

Conclusion

IB should be considered in every infant with rapidly progressing hypotonia and a history of constipation. However rarely, transmission could occur through inhalation of dust particles containing the toxin, therefore it is important to explore all possible sources of exposure. In the case described, timely diagnosis and treatment determined the successful outcome, which highlights the importance of early intervention in managing IB.
Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 HR + HER2- breast cancer: a retrospective analysis
Authors: Kook Yoonwon , Lee Young-jin , Chu Chihhao , Jang Ji Soo , Baek Seung Ho , Bae Soong June , Cha Yoon Jin , Gong Gyungyup , Jeong Joon , Lee Sae Byul , Ahn Sung Gwe
Published: November 2024

Background

HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.

Methods

A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed.

Results

Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172–1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.

Conclusion

Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.
A lightweight deep-learning model for parasite egg detection in microscopy images
Authors: Xu Wenbin , Zhai Qiang , Liu Jizhong , Xu Xingyu , Hua Jing
Published: November 2024

Background

Intestinal parasitic infections are still a serious public health problem in developing countries, and the diagnosis of parasitic infections requires the first step of parasite/egg detection of samples. Automated detection can eliminate the dependence on professionals, but the current detection algorithms require large computational resources, which increases the lower limit of automated detection. Therefore, we have designed a lightweight deep-learning model, YAC-Net, to achieve rapid and accurate detection of parasitic eggs and reduce the cost of automation.

Methods

This paper uses the ICIP 2022 Challenge dataset for experiments, and the experiments are conducted using fivefold cross-validation. The YOLOv5n model is used as the baseline model, and then two improvements are made to the baseline model based on the specificity of the egg data. First, the neck of the YOLOv5n is modified to from a feature pyramid network (FPN) to an asymptotic feature pyramid network (AFPN) structure. Different from the FPN structure, which mainly integrates semantic feature information at adjacent levels, the hierarchical and asymptotic aggregation structure of AFPN can fully fuse the spatial contextual information of egg images, and its adaptive spatial feature fusion mode can help the model select beneficial feature and ignore redundant information, thereby reducing computational complexity and improving detection performance. Second, the C3 module of the backbone of the YOLOv5n is modified to a C2f module, which can enrich gradient information, improving the feature extraction capability of the backbone. Moreover, ablation studies are designed by us to verify the effectiveness of the AFPN and C2f modules in the process of model lightweighting.

Results

The experimental results show that compared with YOLOv5n, YAC-Net improves precision by 1.1%, recall by 2.8%, the F1 score by 0.0195, and mAP_0.5 by 0.0271 and reduces the parameters by one-fifth. Compared with some state-of-the-art detection methods, YAC-Net achieves the best performance in precision, F1 score, mAP_0.5, and parameters. The precision, recall, F1 score, mAP_0.5, and parameters of our method on the test set are 97.8%, 97.7%, 0.9773, 0.9913, and 1,924,302, respectively.

Conclusions

Compared with the baseline model, YAC-Net optimizes the model structure and simplifies the parameters while ensuring the detection performance. It helps to reduce the equipment requirements for performing automated detection and can be used to realize the automatic detection of parasite eggs under microscope images.

Graphical Abstract
Patient and public involvement in the design of an international clinical trial: real world experience
Authors: Simons Gwenda , Jones Helen , Clarke Ian , Davies Firoza , Grealis Stacey , Insch Elspeth , Kahn Hameed , Lloyd Joanne , Richards Al , Rose Hayley , Williams Ruth , de Wit Maarten , Woodcock Clarissa , Romaniuk Leigh , Bardgett Michelle , Pratt Arthur G. , Falahee Marie
Published: November 2024

Background

The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development.

Methods

A 12-month “accelerator” award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research.

Results

Sixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement.

Conclusions

In general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted.
Addressing vaccination gaps among healthcare workers in sub-Saharan Africa: the role of mandatory Hepatitis B vaccination
Authors: Daniel Faithful Miebaka , Ukoaka Bonaventure Michael , Emeruwa Victoria Ezinne , Oti-Ashong Rosette Chidera , Falaiye Gabriel Oluwafemi
Published: November 2024

Hepatitis B virus (HBV) poses a significant public health threat, particularly in developing countries with high endemicity but poor vaccination among healthcare workers (HCWs). Needlestick injuries increase HCWs' risk, yet only about 42% of HCWs are fully vaccinated compared to 97% in high-income countries. Challenges to vaccine uptake include availability, demanding schedules with frequent unit rotations hindering access, high cost of acquiring shots, and stock shortages resulting in missed opportunities. Mandatory, cost-free HBV vaccinations for HCWs, supported by legislation, international aid, and digital reminders, could ensure self-protection and safety while contributing to the global objective of eradicating HBV by 2030.
University Biology Classrooms as Spaces for Anti-racist Work: Instructor Motivations for Incorporating Race, Racism, and Racial Equity Content
Authors: Scheuermann Nicole L. , Idlebird Candice , Kukday Sayali , McCracken Vance J. , Bradley Rachel E. , Bergan-Roller Heather
Published: November 2024

Including race, racism, and racial equity topics makes biology more relevant to society. Incentives to incorporate these topics are lacking, but anti-racist biology instructors are intrinsically motivated to incorporate these topics, and social injustice events make it a priority. We suggest actions to promote this teaching strategy.
Experiences of the COVID-19 pandemic on child and adolescent psychiatric wards: multi-methods investigation
Authors: Holland Josephine , Da-Silva-Ellimah Morenike , Roe James , Morriss Richard ,   CAPSS Scientific Committee, Sayal Kapil
Published: November 2024

Background

Child and adolescent mental health service in-patient beds are unevenly spread throughout England. Where demand outstrips bed availability, young people may be admitted at-distance or to adult psychiatric wards. The COVID-19 pandemic added pressures to already overstretched services. Understanding experiences during this period is vital to inform strategies for future emergencies.

Aims

To investigate the impact of the COVID-19 pandemic on admissions to local, at-distance or adult psychiatric units, from the perspectives of young people, parents/carers and healthcare professionals.

Method

Multi-methods data were collected from February 2021 to September 2022, as part of the Far Away from Home research programme. A 13-month national surveillance study collected information about admissions to general adolescent units >50 miles from home, out-of-region or to adult psychiatric units. Free-text data from respondents (n = 51) were analysed using content analysis. Interviews with young people (n = 30), parents/carers (n = 21) and healthcare professionals (n = 68) were analysed using thematic analysis.

Results

Restrictions during the COVID-19 pandemic affected young people's contact with others; the requirement to self-isolate on admission and following overnight leave felt distressing, and visiting was limited. This disincentivised overnight leave, leading to some discharges being delayed and others feeling rushed and high risk. The COVID-19 pandemic also accelerated the introduction of virtual meetings, enabling community teams and families to be more involved in therapies, meetings and decision-making.

Conclusions

Restrictions imposed during the COVID-19 pandemic were often negatively perceived. However, the increased use of technology was felt to be positive, widening inclusion and mitigating some negative effects of distance on admissions.
Electrostatic-elastic coupling in colloidal crystals
Authors: Wu Hao , Ou-Yang Zhong-Can , Podgornik Rudolf
Published: November 2024

Electrostatic-elastic coupling in colloidal crystals, composed of a mobile Coulomb gas permeating a fixed background crystalline lattice of charged colloids, is studied on the continuum level in order to analyze the lattice-mediated interactions between mobile charges. The linearized, Debye-Hückel–like mean-field equations incorporating a minimal coupling between electrostatic and displacement fields imply an additional effective attractive interaction between mobile charges. For small screening lengths, the interactions between like mobile charges exhibit colloid-lattice–mediated effective interaction, ranging from weak to strong attraction, while for large screening lengths the lattice-mediated interaction is purely repulsive. Continuum theory incorporating the standard lattice elasticity and electrostatics of mobile charges, augmented by the minimal electrostatic-elastic coupling terms, can serve as a baseline for more detailed microscopic models.
Dynamics of droplet adsorption by liquid film on a grooved surface
Authors: Wu Suchen , Wang He , Deng Zilong
Published: November 2024

Understanding the dynamics of droplet adsorption by liquid film on a grooved surface is of great significance for the possible manipulation of dropwise condensation on the grooved surface. In this study, an improved phase-field lattice Boltzmann model is proposed to describe the process of droplet adsorption from the ridge to the liquid film within the channel. The results indicate that the leading edge of the droplet undergoes two accelerations during the adsorption process, obeying the power law of

and

, respectively. The adsorption process between droplets with different sizes and the liquid film exhibits self-similarity characteristics including the same first peak velocity, the similar droplet displacement-time curve and the equal dimensionless spreading length of

. Decreasing the contact angle of the droplet from

to

accelerates the displacement of the leading edge and extends the spreading length. These findings may help reveal the mechanics of droplet adsorption by the liquid film on the grooved surface and thus manipulate the condensation behavior for the heat transfer enhancement.
17α-Hydroxylase/17,20-lyase Deficiency (17-OHD): A Meta-analysis of Reported Cases
Authors: Willemsen Annabelle L , Torpy David J , De Sousa Sunita M C , Falhammar Henrik , Rushworth R Louise
Published: November 2024

Purpose

Homozygous pathogenic variants in the CYP17A1 gene result in defective activity of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase resulting in the clinical syndrome 17-OHD characterized by hypertension, hypokalemia, and disorders of sexual development. Pathogenic variants of CYP17A1 lead to complete or partial loss of enzymatic activity and clinical presentations of varying severity. This study aimed to examine relationships between CYP17A1 genotype and clinical presentation in a global cohort.

Methods

We searched PubMed and Scopus for case reports and cohort studies reporting clinical data on patients with 17-OHD published between 1988 and 2022. Of 451 studies, 178 met inclusion criteria comprising a total of 465 patients. We pooled patient data and examined associations between causative variants and their clinical presentations.

Results

There were 465 unique patients with a mean age of 18.9 (9.0) years, 52.5% (n = 244) were XY and 6.4% (n = 29) were phenotypically male. Homozygous variants were seen in 48.0% (n = 223) of patients. Common clinical presentations were hypertension (57.0%, n = 256), hypokalemia (45.4% n = 211), primary amenorrhea (38.3%, n = 178), cryptorchidism (15.3%, n = 71), and atypical genitalia (14.2%, n = 66). Frequently occurring variants included p.Y329Kfs (n = 86), p.D487_F489del (n = 44), and p.W406R (n = 39). More severe variants, such as p.Y329Kfs, were associated with hypocortisolism (P < .05), combined hypokalemia and hypertension (P < .01), and disordered sexual development (P < .01).

Main conclusion

17-OHD is a rare, frequently misdiagnosed disease. Male patients are typically diagnosed earlier because of genital dysplasia associated with less severe variants, whereas female patients are typically diagnosed later from primary amenorrhea and hypertension. Patients presenting with disordered sexual development and hypertension should be investigated for 17-OHD.
Molecular and Clinical Profiles of Pediatric Monogenic Diabetes Subtypes: Comprehensive Genetic Analysis of 138 Patients
Authors: Zhou Qiaoli , Samadli Sama , Zhang Haoyu , Zheng Xueqin , Zheng Bixia , Zhang Aihua , Gu Wei
Published: November 2024

Background

Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY), and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1% to 4.2% of all diabetes cases. This single-center study with a relatively larger sample size aimed to evaluate the clinical and genetic characteristics of Chinese children with suspected monogenic diabetes (MD) using next-generation sequencing (NGS) methods.

Materials and Methods

Data were collected from 1550 consecutive children diagnosed with diabetes/hyperglycemia at the Endocrinology Department of Children's Hospital of Nanjing Medical University from 2012 to 2023. The genotype and phenotype of 138 children with suspected MD were retrospectively analyzed.

Results

Among 138 children, 16, 97, and 25 patients with NDM, suspected MODY, and SDM, respectively, were assessed by NGS, with a pick-up rate of 87.5%, 57.8%, and 56%, respectively. In total, there was a high pick-up rate of MD, with 58% (80 of 138) among antibody-negative pediatric patients. Pathogenic variants were found in GCK, HNF1A, INS, KCNJ11, INSR, HNF4A, ABCC8, WFS1, ALMS1, HNF1B, BLK, and ZFP57 genes with 13 novel variants in addition to 4 patients with copy number variants. In this cohort, GCK-MODY was the leading cause and the mildest type of MODY. GCK-MODY displayed favorable lipid profile when compared to non-GCK-MODY and MODYX, which might be cardioprotective. Following an accurate genetic diagnosis of diabetes, 19 patients switched from insulin therapy to oral agents or lifestyle interventions.

Conclusion

NGS tests helped to identify the precise etiology of monogenic diabetic patients, which has implications for better individualized management.
Earthquake Preparedness for Operating Room Staff: Lessons Learned From Experiences and the Literature
Authors: Matsumoto Yako , Kinoshita Michiko , Tomiyama Yoshinobu , Tanaka Katsuya
Published: November 2024

Earthquakes pose hazards to health care workers and patients in operating rooms. Proactive planning based on insights gained from past experiences is crucial for enhancing safety. Through a comprehensive literature review, we summarize challenges and lessons learned from real earthquake events to inform the development of effective safety measures in operating rooms. Additionally, we discuss the anesthesiologist’s role in crisis management.
Vestibular Schwannoma Koos Grade I International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS-K1 Study
Authors: Bin-Alamer Othman , Abou-Al-Shaar Hussam , Peker Selcuk , Samanci Yavuz , Pelcher Isabelle , Begley Sabrina , Goenka Anuj , Schulder Michael , Tourigny Jean-Nicolas , Mathieu David , Hamel Andréanne , Briggs Robert G. , Yu Cheng , Zada Gabriel , Giannotta Steven L. , Speckter Herwin , Palque Sarai , Tripathi Manjul , Kumar Saurabh , Kaur Rupinder , Kumar Narendra , Rogowski Brandon , Shepard Matthew J. , Johnson Bryan A. , Trifiletti Daniel M. , Warnick Ronald E. , Dayawansa Samantha , Mashiach Elad , Vasconcellos Fernando De Nigris , Bernstein Kenneth , Schnurman Zane , Alzate Juan , Kondziolka Douglas , Sheehan Jason P.
Published: November 2024

BACKGROUND AND OBJECTIVE:

This investigation evaluates the safety and efficacy of stereotactic radiosurgery (SRS) vs observation for Koos grade I vestibular schwannomas (VS).

METHODS:

In a multicenter study, we retrospectively analyzed data of patients with Koos grade I VS who underwent SRS (SRS group) or were observed (observation group). Propensity score matching was used to equilibrate demographics, tumor size, and audiometric data across groups. The outcome analyzed included tumor control, preservation of serviceable hearing, and neurological function.

RESULTS:

The study matched 142 patients, providing a median follow-up period of 36 months. SRS significantly enhanced tumor control compared with observation, with a 100% control rate at both 5- and 8-year marks in the SRS group vs 48.6% and 29.5% in the observation group at the same time intervals, respectively (P < .001). Preservation of serviceable hearing outcomes between groups showed no significant difference at 5 and 8 years, ensuring a comparable quality of auditory function (SRS 70.1% vs observation 53.4% at 5 years; P = .33). Furthermore, SRS was associated with a reduced likelihood of tinnitus (odds ratio [OR] = 0.46, P = .04), vestibular dysfunction (OR = 0.17, P = .002), and overall cranial nerve dysfunction (OR = 0.49, P = .03) at last follow-up.

CONCLUSION:

SRS management of patients with Koos grade I VS was associated with superior tumor control and reduced odds for cranial nerve dysfunction, while not compromising hearing preservation compared with observation. These findings support the safety and efficacy of SRS as a primary care approach for this patient population.
Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches
Authors: Findlay Andrew R.
Published: November 2024

Treatments for disabling and life-threatening hereditary muscle disorders are finally close to becoming a reality. Research has thus far focused primarily on recessive forms of muscle disease. The gene replacement strategies that are commonly employed for recessive, loss-of-function disorders are not readily translatable to most dominant myopathies owing to the presence of a normal chromosome in each nucleus, hindering the development of novel treatments for these dominant disorders. This is largely due to their complex, heterogeneous disease mechanisms that require unique therapeutic approaches. However, as viral and RNA interference-based therapies enter clinical use, key tools are now in place to develop treatments for dominantly inherited disorders of muscle. This article will review what is known about dominantly inherited disorders of muscle, specifically their genetic basis, how mutations lead to disease, and the pathomechanistic implications for therapeutic approaches.
Borg5 restricts contractility and motility in epithelial MDCK cells
Authors: Cohen David , Fernandez Dawn , Lázaro-Diéguez Francisco , Überheide Beatrix , Müsch Anne
Published: November 2024

The Borg (or Cdc42EP) family consists of septin-binding proteins that are known to promote septin-dependent stress fibers and acto-myosin contractility. We show here that epithelial Borg5 (also known as Cdc42EP1) instead limits contractility, cell–cell adhesion tension and motility, as is required for the acquisition of columnar, isotropic cell morphology in mature MDCK monolayers. Borg5 depletion inhibited the development of the lateral F-actin cortex and stimulated microtubule-dependent leading-edge lamellae as well as radial stress fibers and, independently of the basal F-actin phenotype, caused anisotropy of apical surfaces within compacted monolayers. We determined that Borg5 limits colocalization of septin proteins with microtubules, and that like septin 2, Borg5 interacts with the rod-domain of myosin IIA (herein referring to the MYH9 heavy chain). The interaction of myosin IIA with Borg5 was reduced in the presence of septins. Because septins also mediate myosin activation, we propose that Borg5 limits contractility in MDCK cells in part by counteracting septin-associated myosin activity.
The Impact of Diagnostic Laparoscopy on Upstaging Patients with Siewert II and III Gastroesophageal Junction (GEJ) Cancer
Authors: Alcasid Nathan J. , Fink Deanna , Banks Kian C. , Susai Cynthia J. , Barnes Katherine , Wile Rachel , Sun Angela , Patel Ashish , Ashiku Simon , Velotta Jeffrey B.
Published: November 2024

Background

The efficacy of routine diagnostic laparoscopy with cytologic evaluation for gastroesophageal junction (GEJ) cancer is variable with no set guidelines. We hypothesize that findings from diagnostic laparoscopy in Siewert II and III GEJ tumors may differ, where routine diagnostic laparoscopy with washings yields low upstaging results in Siewert II compared with Siewert III tumors.

Patients and Methods

We reviewed patients with Siewert II/III GEJ cancer from 2012 through 2022 within our integrated health system. Chi-squared, Fisher’s exact, and two-sample Wilcoxon rank-sum tests were utilized. The outcomes measured include likelihood of upstaging, cytology positivity, times to chemotherapy and surgery, and 5-year mortality using a multivariable Cox regression model.

Results

Of 265 patients with Siewert II diagnosis, 116 patients underwent a diagnostic laparoscopy while 149 patients did not. Median time to chemotherapy initiation and definitive surgery were increased among patients with diagnostic laparoscopy, with no difference observed in 5-year survival. For patients with Siewert II and III with a diagnostic laparoscopy, 5% of Siewert II were upstaged, compared with 17% of Siewert III (p = 0.025). Obtaining cytologic washings alone were less likely to be upstaged compared with receiving a biopsy with or without washings (5.2% vs. 17.3%, p = 0.039), and those with Siewert II were less likely than Siewert III to be upstaged after diagnostic laparoscopy (5.2% vs. 17.4%, p = 0.025).

Conclusions

Routine diagnostic laparoscopy yields a low upstaging rate in Siewert II GEJ adenocarcinomas (AC) while delaying treatment with no improvement on mortality. Expediting definitive surgery with selective biopsy in lieu of diagnostic laparoscopy may improve oncologic outcomes.