bluuebunny/crossref_metadata_2025_split huggingface dataset:
A double-blinded randomised controlled trial of vitamin A drops to treat post-viral olfactory loss: study protocol for a proof-of-concept study for vitamin A nasal drops in post-viral olfactory loss (APOLLO)
Authors: Kumaresan Kala , Bengtsson Sara , Sami Saber , Clark Allan , Hummel Thomas , Boardman James , High Juliet , Sobhan Rashed , Philpott Carl 
Published: October 2023

Abstract
Background
Smell loss is a common problem with an estimated 5% of the population having no functioning sense of smell. Viral causes of smell loss are the second most common cause and the coronavirus (COVID-19) pandemic is estimated to have caused 20,000 more people this year to have a lasting loss of smell. Isolation, depression, anxiety, and risk of danger from hazards such as toxic gas and spoiled food are all negative impacts. It also affects appetite with weight loss/gain in two-thirds of those affected. Phantosmia or smell distortion can also occur making most foods seem unpalatable. Smell training has been tried with good results in the immediate post-viral phase. Evidence behind treatment with steroids has not shown to have proven effectiveness. With this, a key problem for patients and their clinicians is the lack of proven effective therapeutic treatment options. Based on previous studies, there is some evidence supporting the regenerative potential of retinoic acid, the metabolically active form of vitamin A in the regeneration of olfactory receptor neurons. It is based on this concept that we have chosen vitamin A as our study comparator.

Aim
To undertake a two-arm randomised trial of intranasally delivered vitamin A vs no intervention to determine proof of concept.

Methods/design
The study will compare 10,000 IU once daily Vitamin A self-administered intranasal drops versus peanut oil drops (placebo) delivered over 12 weeks in patients with post-viral olfactory loss. Potentially eligible patients will be recruited from the Smell & Taste Clinic and via the charity Fifth Sense. They will be invited to attend the Brain Imaging Centre at the University of East Anglia on two occasions, 3 months apart. If they meet the eligibility criteria, they will be consented to enter the study and randomised to receive vitamin A drops or no treatment in a 2:1 ratio. MRI scanning will enable volumetric measurement of the OB and ROS; fMRI will then be conducted using an olfactometer to deliver pulsed odours—phenethylalcohol (rose-like) and hydrogen sulphide (rotten eggs). Participants will also perform a standard smell test at both visits as well as complete a quality-of-life questionnaire. Change in OB volume will be the primary outcome measure.

Discussion
We expect the outputs of this study to enable a subsequent randomised controlled trial of Vitamin A versus placebo. With PPI input we will make the outputs publicly available using journals, conferences, and social media via Fifth Sense. We have already prepared a draft RCT proposal in partnership with the Norwich Clinical Trials Unit and plan to develop this further in light of the findings.

Trial registration
ISRCTN registry 39523. Date of registration in the primary registry: 23rd February 2021.
Microbial antagonists: diversity, formulation and applications for management of pest–pathogens
Authors: Negi Rajeshwari , Sharma Babita , Kaur Simranjeet , Kaur Tanvir , Khan Sofia Sharief , Kumar Sanjeev , Ramniwas Seema , Rustagi Sarvesh , Singh Sangram , Rai Ashutosh Kumar , Kour Divjot , Thakur Neelam , Yadav Ajar Nath 
Published: October 2023

AbstractAgriculture is the backbone of developing countries, which plays an essential role in primary drivers of economy. The increasing use of chemical fertilizers and toxic insecticides endangers the health of human, plant soils, and the environment. Microbial insecticides have been implemented in current scenario for crop protection. Biological agents for pest control have gained more attention in recent year as substitutes for management of pests and pathogens. It provides a sustainable approach to plant health management and assists to minimize the excessive applications of toxic substances. The antagonistic microbes belong to six different phyla including Bacillota, Actinomycetota, Pseudomonadota, Bacteroidota and Mucoromycota. Microbial pesticides have been developed through a number of processes, including extraction of pure culture and screening using effectiveness bioassays under controlled and natural conditions. Biological control agents (BCAs) are recognized to be the most sophisticated technology for environmentally friendly agriculture. The various beneficial BCAs have been reported for the management of plant health, but they required effective acceptance together with the standardization of bioformulation. The present review deals with the recent development of microbial control agents, mechanisms of actions, development of microbial pesticides and their potential applications for agricultural productivity.
Left pulmonary artery sling: why is virtual CT bronchoscopy important? Case report
Authors: Karmakar Deepmala Kalyankumar , Ayyappan Anoop , Valakkada Jineesh , Gopalakrishnan Arun , Dharan Baiju S. 
Published: October 2023

Abstract
Background
Many causes of vascular rings may present as stridor among children. Co-occurrence of tracheal anomaly in left pulmonary artery sling (LPAS) is very common and needs special attention.

Case presentation
We report a case of an infant who presented with expiratory stridor and wheezing. A preliminary chest x-ray revealed no significant findings. CT and virtual bronchoscopy confirmed the diagnosis of LPAS with associated distal tracheal stenosis. He underwent surgical correction with good results in the follow-up period.

Conclusions
Virtual bronchoscopy may help to decide the type of operation and to avoid a potentially invasive bronchoscopy in LPAS.
Increased Resting-State Functional Connectivity in Patients With Autoimmune Addison Disease
Authors: van’t Westeinde Annelies , Padilla Nelly , Fletcher-Sandersjöö Sara , Kämpe Olle , Bensing Sophie , Lajic Svetlana 
Published: October 2023

Abstract

Context
Individuals with autoimmune Addison disease (AAD) take replacement medication for the lack of adrenal-derived glucocorticoid (GC) and mineralocorticoid hormones from diagnosis. The brain is highly sensitive to these hormones, but the consequence of having AAD for brain health has not been widely addressed.

Objective
The present study compared resting-state functional connectivity (rs-fc) of the brain between individuals with AAD and healthy controls.

Methods
Fifty-seven patients with AAD (33 female) and 69 healthy controls (39 female), aged 19 to 43 years were scanned with 3-T magnetic resonance imaging (MRI).

Results
Independent component and subsequent dual regression analyses revealed that individuals with AAD had stronger rs-fc compared to controls in 3 networks: the bilateral orbitofrontal cortex (OFC), the left medial visual and left posterior default mode network. A higher GC replacement dose was associated with stronger rs-fc in a small part of the left OFC in patients. We did not find any clear associations between rs-fc and executive functions or mental fatigue.

Conclusion
Our results suggest that having AAD affects the baseline functional organization of the brain and that current treatment strategies of AAD may be one risk factor.
Fifteen Years of Iodine Prophylaxis in Italy: Results of a Nationwide Surveillance (Period 2015-2019)
Authors: De Angelis Simona , Medda Emanuela , Rotondi Daniela , Masocco Maria , Minardi Valentina , Contoli Benedetta , Possenti Valentina , Sorbo Angela , D’Amato Marilena , Turco Anna Chiara , Pastorelli Alberto Augusto , Stacchini Paolo , Cas Roberto Da , Bagnasco Marcello , Bonofiglio Daniela , Gasperi Maurizio , Meringolo Domenico , Mian Caterina , Moleti Mariacarla , Vermiglio Francesco , Puxeddu Efisio , Taccaliti Augusto , Tonacchera Massimo , Ulisse Salvatore , Dimida Antonio , Rago Teresa , Nazzari Elena , Schiavo Mara , Bossert Irene , Sturniolo Giacomo , Corbetta Carlo , Cereda Cristina , Cappelletti Laura , Camilot Marta , Teofoli Francesca , Ciatti Renzo , Tarsi Elisabetta , Perrotti Nicola , Marasco Onorina , Scozzafava Giovanna , Righetti Francesca , Andò Sebastiano , Catalano Stefania , Cristofaro Mariarosaria , Sorrenti Giovanni , Censi Simona , Morelli Silvia , Baldini Enke , Plutino Giuseppe , Copparoni Roberto , Alonzo Elena , Giacomozzi Claudia , Silano Marco , Olivieri Antonella 
Published: October 2023

Abstract

Context
In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.

Objective
The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program.

Methods
From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values &gt;5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism.

Results
The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 μg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values &gt;5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%.

Conclusion
Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.
Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine
Authors: Maeda Ayumi , Villela-Franyutti Diego , Lumbreras-Marquez Mario I. , Murthy Anarghya , Fields Kara G. , Justice Samuel , Tsen Lawrence C. 
Published: October 2023

BACKGROUND:
The dural puncture epidural (DPE) technique has a faster onset, better sacral spread, and improved bilateral coverage when compared to the conventional epidural (EPL) technique. Whether these qualities translate into a lower bupivacaine dose to provide initial analgesia is unknown. We sought to determine the effective dose of bupivacaine to achieve initial (first 30 minutes) labor analgesia in 90% of patients (ED90) with the DPE and EPL techniques, using a biased-coin, sequential allocation method.

METHODS:
A total of 100 women of mixed parity with term, singleton gestation at ≤5 cm dilation with no major comorbidities were randomized to receive a DPE or an EPL technique. An experienced anesthesiologist performed these techniques and administered an allocated dose of plain bupivacaine diluted with isotonic sterile 0.9% saline to a total volume of 20 mL via the EPL catheter. Bupivacaine doses for each subject were determined by the response of the previous subject, using a biased-coin sequential allocation method, with success defined by a numeric rating scale (NRS) < 3 at 30 minutes. Outcome assessments were performed by an investigator blinded to the technique and bupivacaine dose. Sensory and motor blockade and maternal or fetal side effects were recorded every 5 minutes for the first 30 minutes. The ED90 of bupivacaine with each technique was estimated using centered isotonic regression.

RESULTS:
A total of 95 women were included in the final analysis. The ED90 of bupivacaine was estimated at 29.30 mg (90% confidence interval [CI], 28.55–31.56) with a DPE technique and 45.25 mg (90% CI, 42.80–52.03) with an EPL technique.

CONCLUSIONS:
Using a biased-coin, sequential allocation method, the DPE technique requires less bupivacaine to achieve effective initial analgesia (ED90) when compared to the EPL technique.
Cervical Vertebral Bone Quality Score Independently Predicts Distal Junctional Kyphosis After Posterior Cervical Fusion
Authors: Aguirre Alexander O. , Soliman Mohamed A. R. , Kuo Cathleen C. , Ruggiero Nicco , Im Justin , Chintaluru Yaswanth , Khan Ali M. A. , Khan Asham , Hess Ryan M. , Rho Kyungduk , Smolar David E. , Mullin Jeffrey P. , Pollina John 
Published: October 2023

BACKGROUND AND OBJECTIVE:
Posterior cervical fusion is the surgery of choice when fusing long segments of the cervical spine. However, because of the limited presence of this pathology, there is a paucity of data in the literature about the postoperative complications of distal junctional kyphosis (DJK). We aimed to identify and report potential associations between the preoperative cervical vertebral bone quality (C-VBQ) score and the occurrence of DJK after posterior cervical fusion.

METHODS:
The authors retrospectively reviewed records of patients who underwent posterior cervical fusion at a single hospital between June 1, 2010, and May 31, 2020. Patient data were screened to include patients who were >18 years old, had baseline MRI, had baseline standing cervical X-ray, had immediate postoperative standing cervical X-ray, and had clinical and radiographic follow-ups of >1 year, including a standing cervical X-ray at least 1 year postoperatively. Univariate analysis was completed between DJK and non-DJK groups, with multivariate regression completed for relevant clinical variables. Simple linear regression was completed to analyze correlation between the C-VBQ score and total degrees of kyphosis angle change.

RESULTS:
Ninety-three patients were identified, of whom 19 (20.4%) had DJK and 74 (79.6%) did not. The DJK group had a significantly higher C-VBQ score than the non-DJK group (2.97 ± 0.40 vs 2.26 ± 0.46; P < .001). A significant, positive correlation was found between the C-VBQ score and the total degrees of kyphosis angle change (r2 = 0.26; P < .001). On multivariate analysis, the C-VBQ score independently predicted DJK (odds ratio, 1.46; 95% CI, 1.27-1.67; P < .001).

CONCLUSION:
We found that the C-VBQ score was an independent predictive factor of DJK after posterior cervical fusion.
Outcomes of Gamma Knife Radiosurgery for Brain Metastases in the Motor Cortex
Authors: Prasad Shefalika , Alzate Juan Diego , Mullen Reed , Bernstein Kenneth , Qu Tanxia , Silverman Joshua , Kondziolka Douglas 
Published: October 2023

BACKGROUND AND OBJECTIVES:
To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS).

METHODS:
Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data.

RESULTS:
The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm3-12.18 cm3, mean 0.74 cm3) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) (P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage.

CONCLUSION:
SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.
Separation-of-function MCPH-associated mutations in CPAP affect centriole number and length
Authors: Jaiswal Sonal , Sanghi Srishti , Singh Priyanka 
Published: October 2023

ABSTRACT
Centrioles are microtubule-based cylindrical ultrastructures characterized by their definite size and robustness. The molecular capping protein, CPAP (also known as CENPJ) engages its N-terminal region with the centriole microtubules to regulate their length. Nevertheless, the conserved C-terminal glycine-rich G-box of CPAP, which interacts with the centriole inner cartwheel protein STIL, is frequently mutated in primary microcephaly (MCPH) patients. Here, we show that two different MCPH-associated variants, E1235V and D1196N in the CPAP G-box, affect distinct functions at centrioles. The E1235V mutation reduces CPAP centriole recruitment and causes overly long centrioles. The D1196N mutation increases centriole numbers without affecting centriole localization. Both mutations prevent binding to STIL, which controls centriole duplication. Our work highlights the involvement of an alternative CEP152-dependent route for CPAP centriole localization. Molecular dynamics simulations suggest that E1235V leads to an increase in G-box flexibility, which could have implications on its molecular interactions. Collectively, we demonstrate that a CPAP region outside the microtubule-interacting domains influences centriole number and length, which translates to spindle defects and reduced cell viability. Our work provides new insights into the molecular causes of primary microcephaly.
Evolution and divergence of teleost adrenergic receptors: why sometimes ‘the drugs don't work’ in fish
Authors: Joyce William , Warwicker Jim , Shiels Holly A. , Perry Steve F. 
Published: October 2023

ABSTRACT
Adrenaline and noradrenaline, released as hormones and/or neurotransmitters, exert diverse physiological functions in vertebrates, and teleost fishes are widely used as model organisms to study adrenergic regulation; however, such investigations often rely on receptor subtype-specific pharmacological agents (agonists and antagonists; see Glossary) developed and validated in mammals. Meanwhile, evolutionary (phylogenetic and comparative genomic) studies have begun to unravel the diversification of adrenergic receptors (ARs) and reveal that whole-genome duplications and pseudogenization events in fishes results in notable distinctions from mammals in their genomic repertoire of ARs, while lineage-specific gene losses within teleosts have generated significant interspecific variability. In this Review, we visit the evolutionary history of ARs (including α1-, α2- and β-ARs) to highlight the prominent interspecific differences in teleosts, as well as between teleosts and other vertebrates. We also show that structural modelling of teleost ARs predicts differences in ligand binding affinity compared with mammalian orthologs. To emphasize the difficulty of studying the roles of different AR subtypes in fish, we collate examples from the literature of fish ARs behaving atypically compared with standard mammalian pharmacology. Thereafter, we focus on specific case studies of the liver, heart and red blood cells, where our understanding of AR expression has benefited from combining pharmacological approaches with molecular genetics. Finally, we briefly discuss the ongoing advances in ‘omics’ technologies that, alongside classical pharmacology, will provide abundant opportunities to further explore adrenergic signalling in teleosts.
Oxidative damage varies in response to bacterial, fungal and viral antigen challenges in bats
Authors: Costantini David , Schad Julia , Czirják Gábor Á. , Voigt Christian C. 
Published: October 2023

ABSTRACT
The immune system plays an important role in defending against pathogens and regulating physiological homeostasis, but the strength of the immune responses depends on the type of pathogen. The immune system of bats shows a high variability in responsiveness towards various pathogens; they can safely harbor certain pathogens that are highly lethal to other mammals. Oxidative stress may act as a pathophysiological cellular mechanism mediating the immunological function of bats because of its potentially detrimental effects on physiological homeostasis, fertility and longevity. By experimentally exposing greater mouse-eared bats (Myotis myotis) to three antigens, it was previously shown that animals reacted immunologically most strongly to bacterial and viral antigens, but not to fungal ones. As a follow up, in this study we observed that both bacterial and fungal antigens induced a significant increase of plasma oxidative damage, whereas viral antigens did not cause any increase of plasma oxidative damage at all albeit the mild immune response. Thus, experimental bats were able to avoid oxidative stress only in the face of a viral antigen, possibly by dampening inflammatory signalling. Bats may be able to handle viral infections and live well beyond expectations by reducing the detrimental effects of molecular oxidation.
Measures of puberty in the Avon Longitudinal Study of Parents and Children (ALSPAC) offspring cohort
Authors: Golding Jean , Iles-Caven Yasmin , Northstone Kate , Fraser Abigail , Heron Jon 
Published: October 2023

Background: When studying the development of children through the preteen years into adolescence, it is often important to link features of their physical and mental health to the stage of puberty at the time. This is complex since individuals vary substantially in the ages at which they reach different pubertal milestones. Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is an ongoing longitudinal cohort study based in southwest England that recruited over 14000 women in pregnancy, with expected dates of delivery between April 1991 and December 1992. From 1999, information on puberty was collected using a number of different methods : (a) A series of annual questionnaires were administered when the index children were aged between eight and 17 years; these were mainly concerned with the physical changes associated with puberty; (b) identification of the age at peak height growth using the SITAR methodology; and (c) retrospective information from the girls on their age at onset of menstruation (menarche). Results: The advantages and disadvantages of each method are discussed. Conclusions: The data are available for analysis by interested researchers.