The side-chain has a significant effect on the optical properties and aggregation behaviors of the organic small molecule acceptors, which becomes an important strategy to optimize the photovoltaic performance of organic solar cells (OSCs). In this work, we designed and synthesized three novel nonfused ring electron acceptors (NFREAs) OC4-4Cl-Ph, OC4-4Cl-Th and OC4-4Cl-C8 with hexylbenzene, hexylthiophene and octyl side chains on the π-bridge units. Compared with OC4-4Cl-Ph and OC4-4Cl-Th, OC4-4Cl-C8 with linear alkyl side chain has more red-shift absorption, which is conducive to obtaining higher short-circuit current density. Additionally, the OC4-4Cl-C8 film exhibits a longer exciton diffusion distance and the D18:OC4-4Cl-C8 blend film displays faster hole transfer, weaker bimolecular recombination, and more efficient exciton transport. Furthermore, the D18:OC4-4Cl-C8 blend films can form good nano fibril-like interpenetrating networks, which can facilitate exciton dissociation and charge transport. Finally, OC4-4Cl-C8 based devices can generate an excellent PCE of 16.56%, which is much higher than OC4-4Cl-Ph (12.29%) and OC4-4Cl-Th based (11.00%) ones, being the highest PCE among the NFREA based binary devices. All in all, we have demonstrated that side-chain engineering is an efficient way to achieve high-performance NFREAs.
Amyloid-β peptide (Aβ) oligomers, characteristic symptom of Alzheimer’s disease (AD), have been identified as the most neurotoxic species and significant contributors to neurodegeneration in AD. However, due to their transient and heterogeneous nature, the high-resolution structures and exact pathogenic processes of Aβ oligomers are currently unknown. Using light-controlled molecular tweezers (LMTs), we describe a method for precisely capturing specific Aβ oligomers produced from synthetic Aβ and AD animal models. Light irradiation can activate LMTs, which are composed of two Aβ-targeting pentapeptides (KLVFF) motifs and a rigid azobenzene (azo) derivative, to form a tweezer-like cis configuration that preferentially binds to specifc oligomers matching the space of the tweezers via multivalent interactions of KLVFF motifs with the oligomers. Surprisingly, cis-LMTs can immobilize the captured oligomers in transgenic Caenorhabditis elegans (C. elegans) in vivo under light irradiation. The LMTs may serve as spatiotemporally controllable molecular tools to extract specific native oligomers for the structure and function studies via their reversible photoisomerization, which would improve the understanding of the toxic mechanisms of Aβ oligomers and development of oligomer-targeted diagnosis and therapy.
Background: Pre-eclampsia is a hypertensive disorder of pregnancy which, left untreated, can cause significant foeto-maternal morbidity. Accordingly, the National Institution for Health and Care Excellence (NICE) recommends that high-risk women be prescribed daily prophylaxis with 75-150mg aspirin from twelve weeks’ gestation until delivery. NICE stratifies risk using eleven maternal risk factors; however, no secondary research has been published evaluating the diagnostic accuracy of this algorithm. Objectives: Quantify the sensitivity and specificity of the NICE risk‑stratification algorithm in predicting pre‑eclampsia in pregnant women ≥16 years. Search Strategy: PubMed, Cochrane Library and SCOPUS. PROSPERO Registration: CRD42023437261. Selection Criteria: Papers with a CBEM Level of Evidence ≤4, published 2010‑2023. Data Collection and Analysis: 20 eligible studies consisting of 892,061 pregnancies were analysed. Logit-transformed sensitivities and specificities were modelled as bivariate distributions with random effects. Main Results: Maximum likelihood estimates for the NICE algorithm’s sensitivity and specificity were 44.7% (95% CI 32.3 – 57.8) and 88.0% (95% CI 87.4-88.7), respectively. There was significant heterogeneity between the studies in this analysis (χ 2(17) = 85.05 (p<.0001), I 2=99.8%) and, consequently, a low degree of certainty in these estimates. Conclusions: The NICE risk‑stratification algorithm performs remarkably poorly when used to predict pre‑eclampsia in any of three gestational categories. Clinicians should advise women that around 1 in 5 high-risk patients and 1 in 25 low-risk patients go on to develop pre‑eclampsia. However, future studies will likely alter these values and the confidence therein. Funding: None Key Words: Pre-eclampsia, High-risk Pregnancy, Sensitivity and Specificity, Predictive Value of Tests, Clinical Decision Rules.
Spontaneous Spinal Cord Herniation with Post-operative paraplegia- A case report with 10-year follow-upAbstract:Background: Spinal cord herniation is an uncommon diagnosis in the field of spine surgery. The usual presentation of spontaneous spinal cord herniation is in the form of progressive Brown-Sequard syndrome. We describe a case of a 37-year-old male with progressive back pain and sensory deficits due to spinal cord herniation and a post-operative complication associated with reduction of the hernia.Case description: A 37-year-old male presented with insidious onset upper back pain and altered sensations of pain and temperature over the right half of the body below the nipple 2 months before the examination. The patient did not have motor weakness of lower limbs, abnormal/ involuntary movements, or loss of control over the bowel and bladder. MRI of the thoracic spine showed an anterolateral defect(left) at the level of the T2-T3 vertebra. A posterior approach was chosen and the cord with roots was reduced into the dura. The defect was covered by a dural graft (Lyodura) and the wound was closed with a drain insitu. On the 3rd post-operative day, patient developed paraplegia. Patient was treated by exploration and decompression of the hematoma that compressed spinal cord. The deficits were completely recovered at one-month follow-up.Conclusion: Patients with spinal cord herniation and neurologic deficits when treated timely with reduction of the hernia, have good outcomes. The drain should be removed only when the treating team is satisfied regarding the lack of ongoing hemorrhage. The recovery was maintained till the last follow-up at 10 years.Key words: spontaneous spinal cord herniation, spinal cord defect, paraplegia, Brown-Sequard syndrome
Background and Objectives: Initially developed as immunosuppressive agents, mTOR inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition. Methods: This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1181 total patients and 315 infections (in 290 unique patients) were ultimately included. Results: The majority of infections were viral upper respiratory (n=137, 54%), followed by pneumonia (n=52, 20%), and cutaneous infections (n=20, 8%). There were 6 total infection-related fatalities, which all occurred in patients younger than 2 years. Only 1 case of Pneumocystis jirovecii pneumonia (PJP) was reported. This was in an infant with KHE who was also treated with steroids and did not receive PJP prophylaxis. Almost 1/3 (n=95, 32%) of infectious complications were graded 3 to 4 according to CTCAE criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports. Conclusions: Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.
While the survival of children with cancer has improved over time, infection remains a major morbidity and mortality risk. We conducted a systematic literature review to determine the unmet needs in diagnosing infection in immunocompromised children with cancer. The comprehensive search strategy followed the guidelines established by the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement and spanned multiple bibliographic databases and other public sources from January 1, 2012–June 23, 2022. From 5,188 records, 34 unique pediatric-focused studies met inclusion criteria. This review highlights the lack of published data on infectious disease testing in pediatric oncology patients and the need for well-designed clinical impact and cost-effectiveness studies of both existing and novel diagnostic platforms. Such studies are necessary to optimize diagnostic and antimicrobial stewardship, leading to improvement in patient outcomes.
Motor adaptations are responsible for recalibrating actions and facilitating the achievement of goals in an ever-changing environment. Once consolidated, the decay of motor adaptation is a process affected by available sensory information during deadaptation. However, the cortical response to task error feedback during the deadaptation phase has received little attention. Here, we explored changes in brain cortical responses due to feedback of task-related error during deadaptation. Twelve healthy volunteers were recruited for the study. Right hand movement and EEG were recorded during repetitive trials of a hand reaching movement. A visuomotor rotation of 30° was introduced to induce motor adaptation. Volunteers participated in two experimental sessions organized in baseline, adaptation, and deadaptation blocks. In the deadaptation block, the visuomotor rotation was removed, and visual feedback was only provided in one session. Performance was quantified using angle end-point error, mean speed, and movement onset time. Non-parametric spatiotemporal cluster-level permutation test was used to analyze the EEG recordings. During deadaptation, participants experienced a greater error reduction when feedback of the cursor was provided. The EEG responses showed larger activity in the left centro-frontal parietal areas during the deadaptation block when participants received feedback, as opposed to when they did not receive feedback. Centrally distributed clusters were found for the adaptation and deadaptation blocks in the absence of visual feedback. The results suggest that visual feedback of the task-related error activates cortical areas related to performance monitoring. Different neural circuits contribute to the deadaptation process depending on the available surrounding information.
Scientific outreach activities play an important role in disseminating knowledge, connecting the general public to research and breaking down scientific scepticism barriers. However, the vision impaired community is often disadvantaged when the most common audio-visual approach of scientific communication is applied. Here we integrated tactile clues in the scientific communication of immune processes involved in the autoimmune skin disease psoriasis. We encouraged participation of the vision impaired community by engagement with tactile scientific origami art, a haptic poster and wood carved molecular models. Readily accessible science communication that engages a number of senses is a critical step towards making science more inclusive, and engaging for individuals with a wide range of sensory abilities. The Sensory Science approach aligns with the principles of equity, diversity, and inclusion and helps create a more informed and scientifically literate public.
Simulation and optimization of chemical flowsheets rely on the solution of a large number of non-linear equations. Finding such solutions can be supported by constructing machine-learning based surrogates, relating features and outputs by simple, explicit functions. In order to generate training data for those surrogates computationally efficiently, schemes to adaptively sample the feature space are mandatory. In this article, we present a novel family of utility functions to favor an adaptive, Bayesian exploration of the feature space in order to identify regions that are convergent, fulfill customized inequality constraints and are Pareto-optimal with respect to conflicting objectives. The benefit is illustrated by small toy-examples as well as by industrially relevant chemical flowsheets.
We report on the spectroscopic investigation of common bacteria encountered in biopharmaceutical industries with spectroscopic definition and specificity using mid-infrared laser spectroscopy. This study describes the detection of three different bacteria species using quantum cascade laser spectroscopy coupled to a grazing angle probe (QCL-GAP). Stainless steel substrates were used as support for the bacterial samples. QCL-GAP spectroscopy was assisted by multivariate analysis (MVA) to assemble a powerful spectroscopic technique with classification, identification, and quantification resources. The bacterial species analyzed, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus, were used to challenge the technique’s capability to discriminate microorganisms from the same family. Principal component analysis and partial least squares-discriminant analysis differentiated between the bacterial species using QCL-GAP. Spectral differences in the bacterial membrane were used to determine if these microorganisms were present in the samples analyzed. Results herein provided effective discrimination for the bacteria under study with high sensitivity and specificity values.
IntroductionMultiple sclerosis is an infrequent inflammatory disease of the central nervous system (CNS) that is distinguished by its assorted clinical and radiological presentations [1, 2]. Tumefactive demyelination, or tumefactive multiple sclerosis, stands apart as a distinctive entity within this spectrum. Demyelinating lesions in the central nervous system (CNS) are a sign of these diseases. These lesions can be big, measuring 2 cm or more in diameter, or small, measuring between 0.5 cm and 2 cm, but have the potential to cause mass effects. This unique feature may result in these lesions being initially misidentified as tumor-like space-occupying lesions; however, they typically exhibit a characteristic appearance on radiographic imaging and are clinically benign [3–5]. Tumefactive demyelination, which is distinct from multiple sclerosis, occurs at an estimated rate of about 1-2 per 1000 cases of MS, although some studies propose a higher incidence ranging from 1.4% to 8% [6–7]. However, tumefactive demyelinating lesions can occur concurrently with autoimmune diseases (e.g., Sjogren disease, lupus erythematosus, neuromyelitis optica), infectious diseases (e.g., HIV), malignancy (e.g., renal cell carcinoma), drug-related conditions (e.g., tacrolimus, fingolimod), and postinfectious conditions (e.g., acute disseminated encephalomyelitis, acute hemorrhage leukoencephalitis). Tumefactive demyelination can show up on its own at the start of a disease or as other diseases progress, but the pathophysiology of how it happens is not well understood. On magnetic resonance imaging (MRI) scans, these lesions can appear either as a single large lesion or several lesions exhibiting varying degrees of contrast enhancement. We present here a case study involving a thirty-year-old female who presented with a fever lasting three days followed by Wernicke’s aphasia without right-sided weakness and whose MRI findings were consistent with tumefactive brain demyelination.
Most foundational work on the evolution and migration of plant species relies on genomic data from contemporary samples. Ancient plant samples can give us access to allele sequences and distributions on the landscape dating back to the mid Holocene or earlier (Gugerli et al., 2005). Nuclear DNA from ancient wood, however, has been mostly inaccessible until now. In a From the Cover article in this issue of Molecular Ecology, Wagner et al. (2023) present the first nuclear genomes from ancient to subfossil oak wood, including two samples dated to the 15th century and one that dates to more than 3,500 years ago. These first assembled nuclear genomes from ancient trees open the possibility for investigating species adaptation, migration, divergence, and hybridization in the deep past. They pave the way for what we hope will be a new era in the use of paleogenomics to study Holocene tree histories.
Ecological divergence due to habitat difference plays a prominent role in the formation of new species but the genetic architecture during ecological speciation and the mechanism underlying phenotypic divergence remain less understood. Two wild rice species (O. rufipogon and O. nivara) are a progenitor-derivative species pair with ecological divergence and provide a unique system for studying ecological adaptation/speciation. Here, we constructed a high-resolved linkage map and conducted a quantitative trait locus (QTL) analysis of 19 phenotypic traits using an F2 population generated from a cross between the two wild rice species. We identified 113 QTLs associated with interspecific divergence of 16 quantitative traits, with effect sizes ranging from 1.61% to 34.1% in terms of the percentage of variation explained (PVE). The distribution of effect sizes of QTLs followed a negative exponential, suggesting that a few genes of large effect and many genes of small effect were responsible for the phenotypic divergence. We observed 18 clusters of QTLs (QTL hotspots) on 11 chromosomes, significantly more than that expected by chance, demonstrating the importance of coinheritance of loci/genes in ecological adaptation/speciation. Analysis of effect direction and v-test statistics revealed that interspecific differentiation of most traits was driven by divergent natural selection, supporting the argument that ecological adaptation/speciation would proceed rapidly under coordinated selection on multiple traits. Our findings provide new insights into the understanding of genetic architecture of ecological adaptation and speciation in plants and helps effective manipulation of specific genes or gene cluster in rice breeding.
Recent work indicates that feralisation is not a simple reversal of domestication, and therefore raises questions about the predictability of evolution across replicated feral populations. In the present study we compare genes and traits of two independently established feral populations of chickens (G. gallus) that inhabit archipelagos within the Pacific and Atlantic regions to test for evolutionary parallelism and/or divergence. We find that these two feral populations share close genetic similarities despite the lack of any current gene flow between them. Next, we used genome scans to contrast the targets of feralisation (selective sweeps) between the two independently feral populations from Bermuda and Hawaii. Three sweep loci (each identified by multiple detection methods) were shared between feral populations, and this overlap is inconsistent with a null model in which selection targets are randomly distributed throughout the genome. In the case of the Bermudian population, many of the genes present within the selective sweeps were either not annotated or of unknown function. Of the nine genes that were identifiable, five were related to behaviour, with the remaining genes involved in bone metabolism, eye development, and the immune system. Our findings suggest that a subset of feralisation loci (i.e. genomic targets of recent selection in feral populations) are shared across independently-established populations, raising the possibility that feralisation involves some degree of parallelism or convergence. A clearer understanding of whether these reflect selection for similar functional traits (‘feralisation syndromes’) will require elucidating genotype-phenotype relationships in any populations being compared.
Alemtuzumab‐induced petechiae and epistaxis in a patient with relapsing remitting multiple sclerosis; A case report Farhad Mahmoudi1*, Sayed Ali Emami1, Farid Masaeli1, Najmeh Rayatpisheh21 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran2School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, IranCorresponding author*Farhad MahmoudiSchool of Medicine,Isfahan University of Medical Sciences,Isfahan, IranEmail: firstname.lastname@example.orgAbstract: This case report presents a 58-year-old woman with Multiple Sclerosis (MS) who developed petechiae and epistaxis, rare side effects following Alemtuzumab treatment. While these reactions are infrequent, heightened awareness among healthcare providers is essential as Alemtuzumab gains popularity in MS treatment. Recognizing and managing such hypersensitivity reactions promptly is crucial for improved patient care. 1.Introduction Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system. The course of the disease varies among individuals, leading to a wide range of symptoms and patterns of presentation. Additionally, there are other conditions, such as radiologically isolated syndrome, which can progress to MS(1). While there is no curative therapy for this condition, certain drugs can modify the course of the disease and improve the prognosis and quality of life for patients.Disease-modifying treatments (DMTs) are the preferred treatment option for patients with MS. Alemtuzumab is an intravenously administered DMT drug that has been available since 2014 for the treatment of patients with multiple sclerosis who have not responded adequately to two or more DMTs. It is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the CD52 antigen on B and T lymphocytes, depleting them from the bloodstream. This drug has been described as a safe and effective treatment with minimal side effects for patients with relapsing-remitting multiple sclerosis.(2)While there are few studies on the cutaneous adverse effects of Alemtuzumab, in this study, we report the first case of an MS patient treated with Alemtuzumab who developed drug-induced petechiae and epistaxis.2. Case presentationA 58-year-old Caucasian woman with relapsing-remitting multiple sclerosis, who had no previous medical conditions, presented to the emergency department due to muscle spasms and stiffness in her right foot. Neurological examination revealed weakness in her right lower limb with 3/5 muscle strength. She was diagnosed with MS at the age of 26 through an MRI and had previously been on weekly Interferon-beta (IFNb) treatment. During acute MS attacks, she received intravenous corticosteroids. Despite being on disease-modifying therapies (DMTs), she experienced more relapses in the last year, and her Expanded Disability Status Scale (EDSS) was 3. During the current hospitalization, the patient underwent brain and cervical spinal MRI, which revealed the appearance of new periventricular white active plaques in addition to previous black old lesions.Considering the progression of her disease condition, she was started on treatment with Alemtuzumab at a dose of 12mg/day IV. There were no drug reactions, and after completing the treatment, her muscle spasms and stiffness resolved, and the patient was discharged from the hospital.The day after, the patient came to the hospital to receive the second dose of the drug. While receiving the treatment, her condition remained stable, and she did not experience any notable symptoms. However, one day after finishing the first dose, the patient started to experience a gradual appearance of petechiae on her upper and lower limbs, chest, shoulders, and back. Moreover, a few minutes later, she developed epistaxis. Her blood pressure and heart rate were 127/73 and 87, respectively. The patient denied any previous history of eczema, skin issues, or respiratory allergies.Dermatology was consulted to investigate the possible causes of petechiae, and ENT was consulted to manage and evaluate the epistaxis. Despite applying pressure to the nostrils and placing ice on the forehead, the epistaxis did not cease. Consequently, the patient underwent posterior nasal packing, which successfully halted the bleeding.
Background: Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end-organ disease. Methods: Therefore, we conducted a cross-sectional study that evaluated the prevalence of elevated TRV ≥ 2.5 m/s and its associations with renal and cerebrovascular outcomes in children with SCD 1-21 years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical and Research Intervention Program (SCCRIP) cohort at St. Jude Children’s Research hospital. We hypothesized that patients with sickle cell disease with elevated TRV would have higher odds of having either albuminuria or cerebrovascular disease. Results: We identified 166 children from the UAB cohort (mean age: 13.49 ± 4.47 years) and 325 children from the SCCRIP cohort (mean age: 13.41 ± 3.99 years) with echocardiography. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (OR 1.88 (95% CI: 1.12- 3.15)) and persistent albuminuria (OR: 1.81 (95% CI: 1.07– 3.06)) after adjusting for age, sex, treatment, and site. Conclusion: This cross-sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end-organ disease.