Unusual Association of Partial Fanconi Syndrome and Tumor-Induced Osteomalacia Revealed by Multiple Vertebral Fractures.

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome caused by a mesenchymal tumor secreting a phosphaturic hormone called FGF23. Patients present with bone pain, fragility fractures and muscle weakness. Biochemical results show hypophosphatemia, raised serum alkaline phosphatase and reduced calcitriol.

Sex-related changes in lactate dehydrogenase A expression differently impact the immune response in melanoma.

Melanoma is more aggressive in male patients than female ones and this is associated with sexual dimorphism in immune responses. Taking into consideration the impact tumour metabolic alterations in affecting the immune landscape, we aimed to investigate the effect of the sex-dependent metabolic profile of melanoma in re-shaping immune composition. Melanoma is characterised by Warburg metabolism, and secreted lactate has emerged as a key driver in the establishment of an immunosuppressive environment.

Asymmetric Synthesis of Inherently Chiral Tetraoxacalix[2]arene[2]pyridines via SNAr-based Cross-cyclotetramerization.

Potassium phosphate-promoted cross-cyclotetramerization of 2,6-dichloro-3-nitropyridine 1 with resorcinol derivatives 2 gave rise to thermodynamically favored 1,3-alternate tetraoxacalix[2]arene[2]pyridines and kinetically controlled 1,2-alternate isomers. The kinetic product could convert into its 1,3-alternate conformational isomer by a macrocycle to macrocycle conversion pathway. Enantiomerically enriched C2-symmetric inherently chiral tetraoxacalix[2]arene[2]pyridines were synthesized via a Cinchonine-derived chiral phase-transfer catalyst (PTC).

Real-world comparative effectiveness of sacubitril/valsartan versus RAS inhibition alone in patients with de novo heart failure.

Aims: Large-scale, real-world data on early initiation of sacubitril/valsartan in patients newly diagnosed (de novo) with HF with reduced ejection fraction (HFrEF) are limited. We examined the effectiveness of sacubitril/valsartan versus angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) on all-cause and cause-specific hospitalizations among patients with de novo HFrEF from the Optum® dataset in the United States.

Methods: This retrospective cohort study included adult patients with de novo HFrEF (diagnosed ≤30 days) with left ventricular ejection fraction (LVEF) ≤40% who were first prescribed with sacubitril/valsartan or ACEi/ARB from 1 January 2016 to 31 March 2020.

The Modified Coronally Advanced Tunnel Technique for Coverage of Mucosal Recessions at Dental Implants.

Objectives: To clinically evaluate the outcomes following surgical coverage of single peri-implant mucosal recessions in the aesthetic maxillary area by means of the modified coronally advanced tunnel (MCAT) and subepithelial connective tissue graft (SCTG).

Materials And Methods: Eleven systemically healthy non-smoking patients (8 females) each presenting a single peri-implant mucosal recession in the anterior maxillary region were consecutively treated with MCAT in conjunction with SCTG. In all cases, the facial recession was associated with an impaired aesthetic appearance.

A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study.

Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood proteins (EpiScores).

The Hidden Value of Adult Informal Care in Europe.

The hidden value of adult informal care (IC) refers to the unaccounted value of informal care in overall costs of long-term care (LTC) estimates. This paper estimates the net value of adult IC in Europe, drawing on a well-being-based methodology. We use an instrumental variable strategy and a longitudinal and cross-country dataset to estimate the causal effect of the extensive and intensive margin of caregiving on subjective well-being.

Comparison of the Histological Structure of an Anterior as well as a Posterior Biopsy From the Human Palate: A Comparative Study.

Aim: To compare the histological structure of biopsies from the anterior and posterior regions of the human palate in order to gain insights into potential differences of soft tissue harvesting sites.

Methods: This comparative study involved 20 participants, from each of whom four samples from the palatal mucosa were collected. The biopsies were histologically processed and subsequently analysed.

Phylogenetic and biochemical drivers of plant species variation in organic compound hydrogen stable isotopes: novel mechanistic constraints.

Significant variation in plant organic compound hydrogen stable isotope (δH) values among species from a single location suggests species biochemistry diversity as a key driver. However, the biochemical mechanisms and the biological relevance behind this species-specific δH variation remain unclear. We analyzed δH values of cellulose and n-alkanes across 179 eudicot species in a botanical garden sampled in 2019, and cellulose, n-alkanes, fatty acids and phytol δH values from 56 eudicot species sampled in 2020.

Clinical practice and outcomes in European pediatric cardiac anesthesia: A secondary analysis of the APRICOT and NECTARINE studies.

Background: Despite advancements in surgical techniques and perioperative care, pediatric cardiac patients remain at an increased risk of adverse events. The APRICOT (2017) study aimed to establish the incidence of severe critical events in children undergoing anesthesia in Europe, while the NECTARINE (2021) study aimed to assess anesthesia practices and outcomes in neonates and infants under 60 weeks postconceptual age. Our goal was to conduct a secondary analysis of the cardiac cohorts from these two studies to determine mortality rates and other outcomes after cardiac procedures at 30 and 90 days, identify factors influencing mortality, illustrate clinical practices, and assess the methodology of the two studies.

Transfer of the Oral Gonadotropin-Releasing Hormone Receptor Antagonist Relugolix Into Breast Milk of Healthy Lactating Women.

Relugolix is an oral gonadotropin-releasing hormone receptor antagonist that suppresses sex steroid hormones and is approved as monotherapy for prostate cancer and as a fixed-dose combination with estradiol/norethindrone for the treatment of endometriosis and uterine fibroids. The aim of this postmarketing study was to determine the pharmacokinetics and quantify the amount of relugolix excreted into breast milk of healthy lactating women. Following a single, oral dose of 40 mg relugolix, breast milk was sampled over 120 h.

Quantitative Benefit-Risk Assessment of Vaccination Against COVID-19: A Systematic Review.

Purpose: With the introduction of COVID-19 vaccines, there has been a proliferation of quantitative benefit-risk assessments (qBRAs). Prior work on other types of vaccines has found that published qBRAs have not always clearly reported methods and/or results needed to assist in the application of the qBRA findings. The aim was to systematically identify, review, and critically assess published COVID-19 vaccine qBRA.

Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.

Glucagon-like peptide-1 (GLP-1), a hormone released from enteroendocrine cells in the distal small and large intestines in response to nutrients and other stimuli, not only controls eating and insulin release, but is also involved in drinking control as well as renal and cardiovascular functions. Moreover, GLP-1 functions as a central nervous system peptide transmitter, produced by preproglucagon (PPG) neurons in the hindbrain. Intestinal GLP-1 inhibits eating by activating vagal sensory neurons directly, via GLP-1 receptors (GLP-1Rs), but presumably also indirectly, by triggering the release of serotonin from enterochromaffin cells.

TR(Acking) Individuals Down: Exploring the Effect of Temporal Resolution in Resting-State Functional MRI Fingerprinting.

Functional brain fingerprinting has emerged as an influential tool to quantify reliability in neuroimaging studies and to identify cognitive biomarkers in both healthy and clinical populations. Recent studies have revealed that brain fingerprints reside in the timescale-specific functional connectivity of particular brain regions. However, the impact of the acquisition's temporal resolution on fingerprinting remains unclear.

How many people in the US are eligible for and respond to checkpoint inhibitors: An empirical analysis.

In 2018, we estimated that eligibility for and response to immune checkpoint inhibitor (ICI) therapies were 44% and 12%, respectively. Since these estimates were published, there have been additional approvals. We sought to provide updated estimates of the percentage of patients with advanced and/or metastatic cancers in the US who are eligible for and respond to immune checkpoint inhibitors (ICIs).

Toe Polydactyly and Supernumerary Nipple: Broadening the Phenotypic Spectrum of STAR Syndrome.

STAR syndrome is a very rare X-linked dominant disorder characterized by the association of toe syndactyly, facial dysmorphism including telecanthus and a broad nasal tip, and anogenital and renal malformations. We hereby report a patient with a novel frameshift mutation in CCNQ, the STAR syndrome causative gene. More importantly, the patient presented hitherto unreported clinical features, namely toe polydactyly in addition to syndactyly, and a supernumerary nipple.

Slow Codes are symptomatic of ethically and legally inappropriate CPR policies.

Although cardiopulmonary resuscitation (CPR) was initially used very selectively at the discretion of clinicians, the use of CPR rapidly expanded to the point that it was required to be performed on all patients having in-hospital cardiac arrests, regardless of the underlying condition. This created problems with CPR being clearly inadvisable for many patients. Do Not Resuscitate (DNR) orders emerged as a means of providing a transparent process for making decisions in advance regarding resuscitation, initially by patients and later also by clinicians.

Conditionally Activated ROS Generation by MMP2/9-Specific C-Based Fluorescence Probes.

A C-coumarin conjugate, covalently connected via a matrix metalloproteinase (MMP2/9)-cleavable peptide linker (Pro-Leu-Gly-Val-Arg-Gly), is developed as a probe for both imaging and photodynamic treatment of MMP2/9-expressing malignant cells. In the synthesized probe, the coumarin fluorescence is completely suppressed intramolecularly by the C moiety, while an intensive fluorescence increase is observed in the presence of MMP2/9 dependent on cleavage of the peptide linker. The specificity of the probe to detect MMP2 is confirmed by control experiments resulting in no emission 1) with a control probe bearing a shuffled peptide (Val-Arg-Leu-Gly-Pro-Gly) or 2) in the presence of an MMP2 inhibitor (1,10-phenantheoline).

Biomarker treatment effects in two phase 3 trials of gantenerumab.

Introduction: We report biomarker treatment effects in the GRADUATE I and II phase 3 studies of gantenerumab in early Alzheimer's disease (AD).

Methods: Amyloid and tau positron emission tomography (PET), volumetric magnetic resonance imaging (vMRI), cerebrospinal fluid (CSF), and plasma biomarkers used to assess gantenerumab treatment related changes on neuropathology, neurodegeneration, and neuroinflammation over 116 weeks.

Results: Gantenerumab reduced amyloid PET load, CSF biomarkers of amyloid beta (Aβ)40, total tau (t-tau), phosphorylated tau 181 (p-tau181), neurogranin, S100 calcium-binding protein B (S100B), neurofilament light (NfL), alpha-synuclein (α-syn), neuronal pentraxin-2 (NPTX2), and plasma biomarkers of t-tau, p-tau181, p-tau217, and glial fibrillary acidic protein (GFAP) while increasing plasma Aβ40, Aβ42.

Taxonomic and phylogenetic biases in translocated angiosperm plant species across European countries.

Conservation translocations are a well-known conservation tool used to reverse the effects of local population extinctions and restore ecosystems. Compared with mammals and birds, plants are underrepresented in translocation programs, and little is known about the potential taxonomic and phylogenetic biases of plant translocation efforts. We aimed to assess how translocated plant species may contribute to the conservation of phylogenetic diversity (PD) among European countries.

Pandanus plastomes decoded: When climate mirrors morphology and phylogenetic relationships.

Premise: Pandanus Parkinson (Pandanaceae) is a large genus of paleotropical tree-like monocots. Previous studies using small DNA regions questioned the monophyly of the seven Pandanus subgenera, but low phylogenetic branch support hindered further investigations. We aimed to (1) test Pandanus subgeneric monophyly, (2) identify clade morphological synapomorphies, (3) investigate correlations between leaf anatomy of water storage tissue and climatic differentiation across clades, and (4) construct hypotheses on the genus' spatiotemporal history.