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Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN. Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs). Results: A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]). Conclusion: In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.

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Ionic Covalent Organic Frameworks are a special subgroup that has risen as promising materials for innovative applications. In parallel, some of the so-called Reticular Innovative Organic compounds (RIOs), which are ionic and non-ionic porous materials have been used with great versatility, for several purposes. In this work, the ionic dye-based RIO-55 was chosen to capture a series of lanthanides (Eu, Gd, Dy, and Tb) from water, observing their affinity with the lattice and the performance of the adsorbent. Thus, the higher adsorbed amount was referred to as Eu3+ (Qmax = 370 mg/g), as well as the best affinity (KL = 5x10-3), following the Langmuir model. The impregnated Eu3+@RIO-55 was used for chemical sensing, capturing dopant molecules (ephedrine and dopamine) from water, showing great performance, even after some reuse cycles. In addition, some initial fluorescence tests were performed using RIO-55 and Eu3+@RIO-55 to observe the spectrum before and after lanthanide impregnation.

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Optical coherence tomography is a noninvasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in the literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT device can generate widefield (centimeters long) imaging of lesions at any location in the oral cavity-but it is challenging for raters to quantitatively assess and score large volumes of data. Leveraging a previously developed epithelial segmentation network, this work develops quantifiable biomarkers that provide direct measurements of tissue properties in three dimensions. We hypothesize that features related to morphology, tissue attenuation, and contrast between tissue layers will be able to provide a quantitative assessment of disease status (dysplasia through carcinoma). This work retrospectively assesses seven biomarkers on a lesion-contralateral matched OCT dataset of the lateral and ventral tongue (40 patients, 70 sites). Epithelial depth and loss of epithelial-stromal boundary visualization provide the strongest discrimination between disease states. The stroma optical attenuation coefficient provides a distinction between benign lesions from dysplasia and carcinoma. The stratification biomarkers visualize subsurface changes, which provides potential for future utility in biopsy site selection or treatment margin delineation.

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In this article, we examine the scientific and sustainable research capacity outcomes of the 'Congo River: user Hydraulics and Morphology' or CRuHM project, a six-year effort supported by the Royal Society's Africa Capacity Building Initiative. This project brought together a consortium of African and UK universities to undertake the first large-scale scientific expeditions to the Congo basin of the modern era in order to better understand the hydraulics and geomorphology of this understudied but globally important river. The river is essential for navigation, irrigation, drinking water and hydroelectric power generation for the 10 basin countries and is critically important for biodiversity and global nutrient, carbon and climatological cycles. This article summarizes the new scientific understanding contributed by the project and the steps taken to ensure a meaningful legacy that would continue long beyond the finite lifetime of available funding. Actions taken to achieve this include establishing a new hydrology research centre at the University of Kinshasa as well as steps to build a wider international community of Congo basin researchers. In this way, we hope to build momentum for future funding initiatives and collaboration.

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The widespread misuse of antibiotics to combat bacterial infections in dairy farming is a global concern contributing to antimicrobial resistance (AMR). To gain insights within small-scale dairy farming, a study was conducted in Nyabihu district of Rwanda from September 2021 to April 2023 to assess practices and factors associated with antibiotic use, investigate antibiotic residues in cow milk and undertake a comprehensive training program to improve quality milk production. A mixed-methods approach, combining cross-sectional and longitudinal intervention studies, involved 42 regular dairy farmers from both open and zero-grazing systems delivering milk to the Union pour la Promotion des Cooperatives des Eleveurs en Nyabihu (UPROCENYA) milk collection center (MCC). Standardized questionnaires and farm interviews were conducted to assess antibiotic use practices while bulk tank milk samples from the same farmers were collected and tested for antibiotic residues using rapid tests over 16 months (8 months before and 8 months after training). Out of 451 bulk tank milk samples tested, 27 samples (6%) contained antibiotic residues, primarily tetracyclines (55.3%) and beta-lactams (44.7%). Before farmers training, 5182.75 l of milk were rejected monthly due to antibiotic residues. Following training, milk rejections decreased to 3192.75 l per month, reflecting 38.35% monthly decrease. However, no statistically significant difference was found by independent t-test (t = 1.441; p = 0.173) between milk rejected before and after training. 97.6% of interviewed farmers reported using antibiotics within six months preceding data collection, with 71.4% primarily used for disease treatment, notably targeting tick-borne diseases (34.0%). Alarming practices included administering antibiotics without referring samples for laboratory examination (100%), disregarding withdrawal periods (88.1%) and administering antibiotics without a veterinary doctor's prescription (85.7%). Factors contributing to these practices included limited farmer's knowledge on antibiotics, easy access to antibiotics in local agro-veterinary shops, and insufficient veterinary services. Antibiotic-laden milk was used to feed calves (38.6%), consumed at home (26.5%), and sold (12.0%). The observed misuse of antibiotics and disregard for antibiotic withdrawal periods pose significant threats to both milk quality and human health. The authors recommend that dairy farmers prioritize animal health monitoring and implementing biosecurity measures to prevent diseases and thus reduce antibiotic usage. Collaborative efforts among stakeholders are highly recommended to enhance capacity building for dairy farmers and support research initiatives. Furthermore, it is strongly suggested to strengthen regulations on the prudent use of antibiotics within the Rwandan food production system to curb antimicrobial resistance across both animal and human populations.

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The discovery of novel chemical classes with novel modes of action for insect control form the backbone of innovation with the goal to deliver much-needed solutions into the hands of growers. Over the last decade, alkyl sulfones have emerged as one of the most versatile new classes and are under intensive investigation in many R&D programs in the industry, with Sumitomo Chemicals recently introducing oxazosulfyl as a first active ingredient to the market. In this review, we discuss some of our strategies to invent novel classes based upon ligand-based design, and also show how incorporation of physical chemical properties into our design enabled us to predictably control chewing and sucking pests. © 2024 Society of Chemical Industry.

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BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. METHODS: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. RESULTS: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). CONCLUSION: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

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BACKGROUND: Tailoring antidepressant drugs (AD) to patients' genetic drug-metabolism profile is promising. However, literature regarding associations of ADs' treatment effect and/or side effects with drug metabolizing genes CYP2D6 and CYP2C19 has yielded inconsistent results. Therefore, our aim was to longitudinally investigate associations between CYP2D6 (poor, intermediate, and normal) and CYP2C19 (poor, intermediate, normal, and ultrarapid) metabolizer-status, and switching/discontinuing of ADs. Next, we investigated whether the number of perceived side effects differed between metabolizer statuses. METHODS: Data came from the multi-site naturalistic longitudinal cohort Netherlands Study of Depression and Anxiety (NESDA). We selected depression- and/or anxiety patients, who used AD at some point in the course of the 9 years follow-up period (n = 928). Medication use was followed to assess patterns of AD switching/discontinuation over time. CYP2D6 and CYP2C19 alleles were derived using genome-wide data of the NESDA samples and haplotype data from the PharmGKB database. Logistic regression analyses were conducted to investigate the association of metabolizer status with switching/discontinuing ADs. Mann-Whitney U-tests were conducted to compare the number of patient-perceived side effects between metabolizer statuses. RESULTS: No significant associations were observed of CYP metabolizer status with switching/discontinuing ADs, nor with the number of perceived side effects. CONCLUSIONS: We found no evidence for associations between CYP metabolizer statuses and switching/discontinuing AD, nor with side effects of ADs, suggesting that metabolizer status only plays a limited role in switching/discontinuing ADs. Additional studies with larger numbers of PM and UM patients are needed to further determine the potential added value of pharmacogenetics to guide pharmacotherapy.

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Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction.

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Despite the availability of various treatment approaches for patients with posttraumatic stress disorder (PTSD), some patients do not respond to these therapies, and novel treatment approaches are needed. This study investigated the efficacy of mifepristone, a glucocorticoid receptor antagonist, in treatment-resistant PTSD patients. Three patients with PTSD who were resistant to standard psychological and pharmacological treatments were prescribed mifepristone (600-1,200 mg/day) for 1 week. A baseline-controlled single-case design was used, involving a 2-week baseline phase (no intervention), a 1-week intervention phase (mifepristone), and a 2-week postintervention phase. The primary outcome measure, self-reported PTSD symptom severity (PCL-5), was assessed daily, with participants providing their own control condition. Two of the three patients experienced a significant reduction in PTSD symptom severity after the intervention phase and no longer met the diagnostic criteria for PTSD. These positive results were maintained during long-term follow-up. These findings support the potential effectiveness of mifepristone in the treatment of patients with treatment-resistant PTSD. However, our findings must be interpreted with caution, and further studies with larger sample sizes and more rigorous designs are necessary to confirm the promising results.

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Optical coherence tomography (OCT) is becoming a more common endoscopic imaging modality for detecting and treating disease given its high resolution and image quality. To use OCT for 3-dimensional imaging of small lumen, embedding an optical scanner at the distal end of an endoscopic probe for circumferential scanning the probing light is a promising way to implement high-quality imaging unachievable with the conventional method of revolving an entire probe. To this end, the present work proposes a hollow and planar micro rotary actuator for its use as an endoscopic distal scanner. A miniaturized design of this ferrofluid-assisted electromagnetic actuator is prototyped to act as a full 360° optical scanner, which is integrated at the tip of a fiber-optic probe together with a gradient-index lens for use with OCT. The scanner is revealed to achieve a notably improved dynamic performance that shows a maximum speed of 6500 rpm, representing 325% of the same reported with the preceding design, while staying below the thermal limit for safe in-vivo use. The scanner is demonstrated to perform real-time OCT using human fingers as live tissue samples for the imaging tests. The acquired images display no shadows from the electrical wires to the scanner, given its hollow architecture that allows the probing light to pass through the actuator body, as well as the quality high enough to differentiate the dermis from the epidermis while resolving individual sweat glands, proving the effectiveness of the prototyped scanner design for endoscopic OCT application.

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INTRODUCTION: In 2013, rituximab was approved in France for the treatment of ANCA-associated vasculitis (AAV). The aim of the study was to compare the treatment and health events of adult incident patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), included before rituximab approval (over 2010-2012, Group 1) and those included after rituximab approval (over 2014-2017, Group 2). METHOD: Data were extracted from the French National Health Insurance database (SNDS) including outpatient health care consumption and hospital discharge forms. Comparisons between inclusion periods were performed using Wilcoxon and χ² tests. Kaplan-Meier method was used to model the duration of treatment induction, maintenance, and off-drug periods. Fine and Gray tests were used to compare treatment phase durations. RESULTS: A total of 694 GPA and 283 MPA patients were included in Group 1, while 668 GPA and 463 MPA patients were included in Group 2. Between the two inclusion periods, the proportions of patients treated with rituximab increased in the induction and maintenance phases whereas treatment with azathioprine declined. These proportions remained stable in the case of methotrexate, cyclophosphamide, and glucocorticoid-treated patients. Frequency of first-time hospitalized infections, diabetes and renal failure during the first year after inclusion increased for both groups. LIMITATIONS OF THE STUDY: This is a retrospective study based on claims data including only 76% of people covered by health insurance in France. The period studied includes the learning phase of using rituximab. This study lacks biological data and precise quantitative analysis for the use of steroids, therefore the criteria for establishing diagnosis and therapeutic choice were unknown. CONCLUSIONS: Introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids or cyclophosphamide.

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Staged nipple-sparing mastectomy (NSM) following mastopexy or breast reduction has become increasingly utilized in patients with large or ptotic breasts. The safety and efficacy of this approach has been demonstrated in recent years. However, the optimal timing between stages has not been established. The authors provide their experience with this staged approach with emphasis on timing between stages. An institutional review board approved this retrospective study. Data of all patients at a single institution who underwent staged NSM following mastopexy or reduction mammaplasty for therapeutic or prophylactic oncologic surgical management from 2016 to 2020 were reviewed. Timing between stages as well as surgical, oncologic, aesthetic, and patient-reported outcomes were evaluated. Nineteen patients (38 breasts) underwent staged NSM following planned mastopexy/breast reduction. The mean time interval between stages was 25 weeks. No patients developed nipple areolar complex necrosis. Infection and hematoma were seen in one breast (2.6%) and seroma in two (5.3%) after NSM. Delayed wound healing was seen in eight breasts (21.1%) after first stage mastopexy/reduction and in 12 breasts (31.6%) after NSM. Skin flap necrosis was noted in two breasts (5.3%) after NSM. No patients developed oncological recurrence. Mean patient-reported post-operative satisfaction and well-being scores were 63 and 67 out of 100, respectively. The authors describe their experience with staged NSM following nipple repositioning procedures. Their results suggest that this procedure can be performed safely with cosmetically favorable results if surgeons wait an average of 25 weeks between first and second stage procedures.

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Covalent organic frameworks (COFs) have gained significant popularity in recent years due to their unique ability to provide a high surface area and customizable pore geometry and chemistry, making them an ideal choice for a wide range of applications. However, exploring COFs experimentally can be arduous and time-consuming due to their immense number of potential structures. As a result, computational high-throughput studies have become an attractive option. Nevertheless, generating COF structures can also be a challenging and time-consuming task. To address this challenge, here, we introduce the pyCOFBuilder, an open-source Python package designed to facilitate the generation of COF structures for computational studies. The pyCOFBuilder software provides an easy-to-use set of functionalities to generate COF structures following the reticular approach. In this paper, we describe the implementation, main features, and capabilities of the pyCOFBuilder, demonstrating its utility for generating COF structures with varying topologies and chemical properties. pyCOFBuilder is freely available on GitHub at https://github.com/lipelopesoliveira/pyCOFBuilder.

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Malaria vector surveillance tools often incorporate features of hosts that are attractive to blood-seeking females. The recently developed host decoy trap (HDT) combines visual, thermal, and olfactory stimuli associated with human hosts and has shown great efficacy in terms of collecting malaria vectors. Synthetic odors and yeast-produced carbon dioxide (CO2) could prove useful by mimicking the human odors currently used in HDTs and provide standardized and easy-to-use olfactory attractants. The objective of this study was to test the attractiveness of various olfactory attractant cues in HDTs to capture malaria vectors. We compared 4 different odor treatments in outdoor field settings in southern Benin and western Burkina Faso: the standard HDT using a human, HDT with yeast-produced CO2, HDT with an artificial odor blend, and HDT with yeast-produced CO2 plus artificial odor blend. In both experimental sites, the standard HDT that incorporated a real human produced the greatest catch of Anopheles gambiae s.l (Diptera: Culicidae). The alternatives tested were still effective at collecting target vector species, although the most effective included CO2, either alone (Benin) or in combination with synthetic odor (Burkina Faso). The trap using synthetic human odor alone caught the fewest An. gambiae s.l. compared to the other baited traps. Both Anopheles coluzzii and Anopheles gambiae were caught by each trap, with a predominance of An. coluzzii. Synthetic baits could, therefore, represent a more standardized and easier-to-deploy approach than using real human odor baits for a robust vector monitoring strategy.

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Although Josias Weitbrecht described the retinacula of the hip joint in his 1742 Syndesmologia, the anatomist Cesare Amantini of Perugia specifically studied the medial retinacula he referred to as the pectineofoveal fold in a late 19th-century monograph. This particular synovial fold stretches from the lesser trochanter to the osteocartilaginous junction of the femoral head along a virtual line connecting the lesser trochanter and the fovea for the ligament of the head. Although mentioned by some anatomists and radiologists, and despite its possible involvement in specific hip joint pathologies (fractures, impingements), it is surprising that Amantini's pectineofoveal fold remains ignored by most anatomy and clinical anatomy books. This study aims to verify if Cesare Amantini effectively drew attention to this synovial fold for the first time and coined the term "pectineofoveal fold," as well as determine whether most classical textbooks (i.e., published from 1890 to 2017) acknowledge the discovery and include it in the description of the hip joint. A possible evolutionary link between this synovial fold and the ambiens and pectineus muscles exists and should be discussed.

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BACKGROUND: The structure and physiology of skin and hair in people of African ancestry are different from other ethnic categories and studies from other continents cannot necessarily be extrapolated to Sub-Saharan Africa (SSA) due to the differences in genetics, lifestyle, climate, cultures, and hair and skin care practices. The aim of this report is to highlight the recent advances in local skin and hair research in SSA from a grant program. METHODS: African Hair and Skin Research Grants from an industrial sponsor were awarded between 2013 and 2022 on five main topics: acne, hair and scalp, keloid scars, atopic dermatitis, and air pollution. A literature search in Scopus identified publications on these topics in African or black skin in SSA and worldwide to provide insight into the impact of the program. RESULTS: The number of publications from around the world on the skin and hair of people of African ancestry has increased significantly over the past 30 years on all five topics, especially as a result studies conducted in the United States. Fewer studies have been conducted in SSA but there has been an increasing number of publications over the past 10 years, especially from South Africa. CONCLUSIONS: Scientific and clinical partnerships between the industry, academia, and public healthcare sectors have contributed to a steady increase in hair and skin publications from SSA, which may be useful for the development of tailored products and public educational campaigns to raise awareness of the risks of using inappropriate products.

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Equiluminant stimuli help assess the integrity of colour perception and the relationship of colour to other visual features. As a result of individual variation, it is necessary to calibrate experimental visual stimuli to suit each individual's unique equiluminant ratio. Most traditional methods rely on training observers to report their subjective equiluminance point. Such paradigms cannot easily be implemented on pre-verbal or non-verbal observers. Here, we present a novel Pupil Frequency-Tagging Method (PFTM) for detecting a participant's unique equiluminance point without verbal instruction and with minimal training. PFTM analyses reflexive pupil oscillations induced by slow (< 2 Hz) temporal alternations between coloured stimuli. Two equiluminant stimuli will induce a similar pupil dilation response regardless of colour; therefore, an observer's equiluminant point can be identified as the luminance ratio between two colours for which the oscillatory amplitude of the pupil at the tagged frequency is minimal. We compared pupillometry-based equiluminance ratios to those obtained with two established techniques in humans: minimum flicker and minimum motion. In addition, we estimated the equiluminance point in non-human primates, demonstrating that this new technique can be successfully employed in non-verbal subjects.

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