bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique genomic alterations in the circulating tumor DNA of patients with solid tumors brain metastases
Authors: Alder Laura , Broadwater Gloria , Green Michelle , Van Swearingen Amanda E D , Lipp Eric S , Clarke Jeffrey Melson , Anders Carey K , Sammons Sarah
Published: April 2024

Background

Although serum circulating tumor DNA (ctDNA) is routine, data from patients with brain metastases (BrMs) is limited. We assessed genomic alterations in ctDNA from patients with solid tumor BrMs in 3 groups: Isolated BrMs with stable extracranial disease (iCNS), concurrent brain and extracranial progression (cCNS), and extracranial progression with no active BrMs (eCNS). We also compared ctDNA alterations between patients with and without BrMs.

Methods

Patients with a Guardant360 ctDNA profile with (n = 253) and without BrMs (n = 449) from the Duke Molecular Registry between January 2014 and December 2020 were identified. Actionable alterations were defined as FDA-recognized or standard-of-care biomarkers. Disease status was determined via investigator assessment within 30 days of ctDNA collection.

Results

Among the 253 patients with BrMs: 29 (12%) had iCNS, 160 (63%) cCNS, and 64 (25%) eCNS. Breast (BC; 12.0%) and non-small cell lung cancer (NSCLC; 76.4%) were the most common tumor types. ESR1 (60% vs 25%, P < .001) and BRCA2 (17% vs 5%, P = .022) were more frequent in BC BrMs. In NSCLC BrMs, EGFR alterations were most frequent in the iCNS group (iCNS: 67%, cCNS: 40%, eCNS:37%, P = .08) and in patients with BrMs (36% vs 17%, P < .001). Sequencing from both brain tissue and ctDNA were available for 8 patients; 7 (87.5%) had identical alterations.

Conclusions

This study illustrates the feasibility of detecting alterations from ctDNA among patients with BrMs. A higher frequency of actionable mutations was observed in ctDNA in patients with BrMs. Additional studies comparing ctDNA and alterations in BrMs tissue are needed to determine if ctDNA can be considered a surrogate to support treatment decisions.
A nurse-led intervention for carers of people with high-grade glioma: A case series of carers reporting high distress
Authors: Halkett Georgia K B , McDougall Emma , Berg Melissa , Clarke Jenny , Dhillon Haryana M , Lobb Elizabeth , Phillips Jane L , Hudson Peter , Faris Mona M , Campbell Rachel , Shaw Joanne , Coyne Elisabeth , Kelly Brian , Ownsworth Tamara , Legge Dianne M , Nowak Anna K
Published: April 2024

Background

Carers play an important role in supporting patients diagnosed with high-grade glioma (HGG). However, this experience is frequently distressing and many carers require support.

Objectives

To describe unmet needs of highly distressed carers of people with HGG and recommendations and referrals made by a nurse to support them within the Care-IS trial.

Methods

Descriptive case series. Carers of people with HGG in the Care-IS trial reporting severe anxiety and/or depression at baseline and/or 4 months and high distress at baseline (during chemoradiotherapy) and at 4 months were included. Carers completed the Partner and Caregiver Supportive Care Needs Scale and Brain Tumor Specific Unmet Needs Survey for carers at baseline, 2, 4, 6, and 12 months. Monthly nurse telephone assessments documented carers’ needs, recommendations, and referrals made. Data are reported descriptively.

Results

Four highly distressed carers were identified (N = 98). Each reported a moderate-high need at ≥1 timepoint for: financial support and/or travel insurance; making life decisions in uncertainty; information about cancer prognosis/likely outcome; and coping with unexpected treatment outcomes. Specific brain tumor unmet needs were: adjusting to changes in personality, mental and thinking abilities, and accessing government assistance. Nurses provided information about treatment, side effects, and practical support. Recommendations for clinical care and referrals to community-based services, and medical specialists were offered.

Conclusions

Highly distressed carers have diverse support needs in many domains, which can change over time. Nurses were critical in identifying carers’ needs, providing support, and making referrals. Carers’ distress and needs require ongoing screening and management.
High-capacity dilithium hydroquinone cathode material for lithium-ion batteries
Authors: Lu Yong , Han Haoqin , Yang Zhuo , Ni Youxuan , Meng Zhicheng , Zhang Qiu , Wu Hao , Xie Weiwei , Yan Zhenhua , Chen Jun
Published: April 2024

Lithiated organic cathode materials show great promise for practical applications in lithium-ion batteries owing to their Li-reservoir characteristics. However, the reported lithiated organic cathode materials still suffer from strict synthesis conditions and low capacity. Here we report a thermal intermolecular rearrangement method without organic solvents to prepare dilithium hydroquinone (Li2Q), which delivers a high capacity of 323 mAh g−1 with an average discharge voltage of 2.8 V. The reversible conversion between orthorhombic Li2Q and monoclinic benzoquinone during charge/discharge processes is revealed by in situ X-ray diffraction. Theoretical calculations show that the unique Li–O channels in Li2Q are beneficial for Li+ ion diffusion. In situ ultraviolet-visible spectra demonstrate that the dissolution issue of Li2Q electrodes during charge/discharge processes can be handled by separator modification, resulting in enhanced cycling stability. This work sheds light on the synthesis and battery application of high-capacity lithiated organic cathode materials.
Towards rational design in electrochemical denitrification by analyzing pH dependence
Authors: Li Huan , Luan Dong , Long Jun , Fu Xiaoyan , Xiao Jianping
Published: April 2024

A small fraction of NOx (<1%) always exists in CO2 feedstock (e.g. exhausted gas), which can significantly reduce the efficiency of CO2 electroreduction by ∼30%. Hence, electrochemical denitrification is the precondition of CO2 electroreduction. The pH effect is a key factor, and can be used to tune the selectivity between N2 and N2O production in electrochemical denitrification. However, there has been much controversy for many years about the origin of pH dependence in electrocatalysis. To this end, we present a new scheme to accurately model the pH dependence of the electrochemical mechanism. An extremely small pH variation from pH 12.7 to pH 14 can be accurately reproduced for N2O production. More importantly, the obviously different pH dependence of N2 production, compared to N2O, can be attributed to a cascade path. In other words, the N2 was produced from the secondary conversion of the as-produced N2O molecule (the major product), instead of the original reactant NO. This is further supported by more than 35 experiments over varying catalysts (Fe, Ni, Pd, Cu, Co, Pt and Ag), partial pressures (20%, 50% and 100%) and potentials (from −0.2 to 0.2 V vs. reversible hydrogen electrode). All in all, the insights herein overturn long-lasting views in the field of NO electroreduction and suggest that rational design should steer away from catalyst engineering toward reactor optimization.
Integrating Medical Librarians Into Infectious Disease Rounding Teams: Survey Results From a Pilot Implementation Study
Authors: Vogel Mia T , Yaeger Lauren H , Burnham Jason P
Published: April 2024

Medical librarians participating as infectious disease rounding team members add value by facilitating knowledge acquisition and dissemination and by improving clinical decision making. This pilot study implementing medical librarians on infectious disease rounding teams was a well-received and beneficial intervention to study participants.
Supporting the quality of deliberative democracy: The contribution of parliamentary library and research services
Authors: Alexander David A
Published: April 2024

Despite the significant role they are created to perform, to act as a source of independent information that informs the legislator about policy-choice, the parliamentary library and research service (PLRS) has been an underexplored component of legislatures within Europe. This article explores the Scottish Parliament Information Centre (SPICe), the Parliament’s combined library and research service, investigating how the unit fulfils an expert function, but also its contribution to deliberative democratic efforts. I find that the PLRS staff member could contribute to supporting the quality of deliberative devices, by lowering the cost of information for participants.
Saving, Inheritance and Future-Making in 1940s Kenya
Authors: Velasco Christian , Willis Justin
Published: April 2024

The colonial state in Kenya offered its African subjects a novel tool for imagining a future life. The Post Office Savings Bank (POSB) was meant to encourage ‘thrift’ — the postponement of consumption — and to play its part in a wider colonial project of turning disparate forms of value into money that could be gathered and used by the state. In practice, Kenya’s POSB was inaccessible and/or unappealing to many people: it disappointed official expectations at the time and has retrospectively been deemed a failure. Yet some colonial subjects, mostly literate men, were able to incorporate the paper passbook issued by the POSB into strategies for managing multiple forms of value in the context of long-standing debates over the circulation of wealth. The numbers written in their savings book became an additional resource in arguments over inheritance and accumulation as they, like others, looked for ways to channel and contain the possibilities created by money and new institutions of finance.
JOINTLESS Maintains Inflorescence Meristem Identity in Tomato
Authors: Huerga-Fernández Samuel , Detry Nathalie , Orman-Ligeza Beata , Bouché Frédéric , Hanikenne Marc , Périlleux Claire
Published: April 2024

JOINTLESS (J) was isolated in tomato (Solanum lycopersicum) from mutants lacking a flower pedicel abscission zone (AZ) and encodes a MADS-box protein of the SHORT VEGETATIVE PHASE/AGAMOUS-LIKE 24 subfamily. The loss of J function also causes the return to leaf initiation in the inflorescences, indicating a pivotal role in inflorescence meristem identity. Here, we compared jointless (j) mutants in different accessions that exhibit either an indeterminate shoot growth, producing regular sympodial segments, or a determinate shoot growth, due to the reduction of sympodial segments and causal mutation of the SELF-PRUNING (SP) gene. We observed that the inflorescence phenotype of j mutants is stronger in indeterminate (SP) accessions such as Ailsa Craig (AC), than in determinate (sp) ones, such as Heinz (Hz). Moreover, RNA-seq analysis revealed that the return to vegetative fate in j mutants is accompanied by expression of SP, which supports conversion of the inflorescence meristem to sympodial shoot meristem in j inflorescences. Other markers of vegetative meristems such as APETALA2c and branching genes such as BRANCHED 1 (BRC1a/b) were differentially expressed in the inflorescences of j(AC) mutant. We also found in the indeterminate AC accession that J represses homeotic genes of B- and C-classes and that its overexpression causes an oversized leafy calyx phenotype and has a dominant negative effect on AZ formation. A model is therefore proposed where J, by repressing shoot fate and influencing reproductive organ formation, acts as a key determinant of inflorescence meristems.
The role of corticosterone in nevirapine-induced idiosyncratic drug-induced liver injury
Authors: Jee Alison , Sernoskie Samantha Christine , Uetrecht Jack
Published: April 2024

Nevirapine, an antiretroviral used in the treatment of HIV, is associated with idiosyncratic drug-induced liver injury (IDILI), a potentially life-threatening adverse drug reaction. Its usage has decreased due to this concern, but it is still widely used in lower-resource settings. In general, the mechanisms underlying idiosyncratic drug reactions (IDRs) are poorly understood, but evidence indicates that most are immune-mediated. There is very limited understanding of the early immune response following administration of drugs associated with IDRs, which likely occurs due to reactive metabolite formation. In this work, we aimed to characterize the links between covalent binding of nevirapine, the development of an early immune response, and the subsequent liver injury using a mouse model. We describe initial attempts to characterize an early immune response to nevirapine followed by the discovery that nevirapine induced the release of corticosterone. Corticosterone release was partially associated with the degree of drug covalent binding in the liver but was also likely mediated by additional mechanisms at higher drug doses. Transcriptomic analysis confirmed metabolic activation, glucocorticoid signaling, and decreased immune activation; GDF-15 also warrants further investigation as part of the immune response to nevirapine. Finally, glucocorticoid blockade preceding the first dose of nevirapine attenuated nevirapine-induced liver injury at 3 weeks, suggesting that acute glucocorticoid signaling is harmful in the context of nevirapine-induced liver injury. This work demonstrates that nevirapine induces acute corticosterone release, which contributes to delayed-onset liver injury. It also has implications for screening drug candidates for IDILI risk and preventing nevirapine-induced IDILI.
A long-snouted marine bonytongue (Teleostei: Osteoglossidae) from the early Eocene of Morocco and the phylogenetic affinities of marine osteoglossids
Authors: Capobianco Alessio , Zouhri Samir , Friedman Matt
Published: April 2024

Osteoglossid bonytongues (arapaimas, arowanas, and relatives) are extant tropical freshwater fishes with a relatively abundant and diverse fossil record. Most osteoglossid fossils come from a 25-million-year interval in the early Palaeogene, when these fishes were distributed worldwide in both freshwater and marine environments. Despite their biogeographic and palaeoecological relevance, and a relative abundance of well-preserved material, the evolutionary relationships between these Palaeogene forms and extant bonytongues remain unclear. Here we describe a new genus of bonytongue from early Eocene marine deposits of Morocco, represented by an articulated, three-dimensionally preserved skull with associated pectoral girdle. This taxon is characterized by an elongated snout, contrasting with the short jaws usually found in marine representatives of the clade. A revision of morphological characters in bonytongues allows us to place this new genus, together with other marine and freshwater Eocene taxa, within crown osteoglossids and closely related to extant arapaimines. The discovery of the new Moroccan taxon hints at a previously underestimated eco-morphological diversity of marine bonytongues, highlighting the diverse trophic niches that these fishes occupied in early Palaeogene seas.
The Influence of Sprinkler and Drip Irrigation on the Incidence and Severity of Bacterial Disease in Onions Grown in Northeast California
Authors: Wilson Rob G. , Aegerter Brenna J. , LaHue Gabe
Published: April 2024

Overhead sprinkler irrigation and its effect on leaf wetness are often referenced as a key factor for bacterial disease spread in onions grown in arid climates. A study was conducted in 2021 and 2022 in Tulelake, California, to compare the incidence and severity of bacterial disease under sprinkler and drip irrigation. The experiment was a split-plot randomized complete block design with drip and solid-set sprinkler irrigation as the main plot treatments and inoculation and no inoculation with plant-pathogenic bacteria as the split-plot treatments. The entire study area was irrigated with solid-set sprinklers from planting until the five-leaf stage to facilitate uniform onion germination and chemigation of herbicides for weed control. After the five-leaf stage, irrigation treatments were imposed for the remainder of the growing season. Total irrigation water amount and irrigation frequency were similar for both irrigation methods. Foliar disease severity and the incidence of bulb rot were 170 and 186% higher, respectively, for solid-set sprinkler compared with drip irrigation. Leaf wetness within the plant canopy during onion bulbing was on average 36% higher in the solid-set sprinkler compared with drip irrigation treatment, whereas relative humidity and temperature were similar between irrigation methods. Drip irrigation maintained lower soil water tension and increased average bulb size by 9% compared with solid-set sprinkler irrigation. This study confirms historical observations that overhead irrigation can extend leaf wetness and increase bacterial disease in onions in arid production areas and highlights the potential benefits of the adoption of drip irrigation.
Associations Between Body Image, Kinesiophobia, and Pain in Women Post-Breast Cancer Treatment
Authors: Smoot Betty J. , Nee Robert J. , Boyd Benjamin S.
Published: April 2024

Background:

The purpose of this study was to evaluate factors associated with body image, kinesiophobia, pain severity, and pain interference in women following breast cancer (BrCA) treatment.

Methods:

A convenience sample of women (n = 160) post-BrCA treatment participated in this cross-sectional study. They completed demographic and clinical questionnaires and performed left/right judgment tasks (LRJTs). Regression analyses evaluated factors associated with the Body Image Scale, Tampa Kinesiophobia Scale, Brief Pain Inventory (BPI) pain severity subscale, and BPI pain interference subscale.

Results:

Higher quality of life (QoL) and older age were associated with better body image, while mastectomy and greater kinesiophobia were associated with worse body image. Higher QoL, better body image, more exercise time (minutes/week), and mastectomy were associated with less fear of movement. Slower chest LRJT response time, higher pain interference, and reconstructive surgery were associated with greater kinesiophobia. Higher QoL was associated with lower pain severity, while more exercise time was associated with higher pain severity. Higher QoL and slower chest LRJT response time were associated with lower pain interference. More exercise time and greater kinesiophobia were associated with greater pain interference.

Conclusion:

Poor body image and kinesiophobia are common in women after unilateral BrCA treatment. This study provides evidence on positive and negative associations between several factors associated with body image, fear of movement, pain severity, and pain interference in women following BrCA treatment. There is benefit to including assessment of these predictors and outcomes in research and clinical settings.
Causal Selection of Covariates in Regression Calibration for Mismeasured Continuous Exposure
Authors: Tang, Wenze , Spiegelman Donna , Liao Xiaomei , Wang Molin
Published: April 2024

Regression calibration as developed by Rosner, Spiegelman, and Willett is used to adjust the bias in effect estimates due to measurement error in continuous exposures. The method involves two models: a measurement error model relating the mismeasured exposure to the true (or gold-standard) exposure and an outcome model relating the mismeasured exposure to the outcome. However, no comprehensive guidance exists for determining which covariates should be included in each model. In this article, we investigate the selection of the minimal and most efficient covariate adjustment sets under a causal inference framework. We show that to address the measurement error, researchers must adjust for, in both measurement error and outcome models, any common causes (1) of true exposure and the outcome and (2) of measurement error and the outcome. We also show that adjusting for so-called prognostic variables that are independent of true exposure and measurement error in the outcome model, may increase efficiency, while adjusting for any covariates that are associated only with true exposure generally results in efficiency loss in realistic settings. We apply the proposed covariate selection approach to the Health Professional Follow-up Study dataset to study the effect of fiber intake on cardiovascular disease. Finally, we extend the originally proposed estimators to a nonparametric setting where effect modification by covariates is allowed.
Interpretations of Studies on SARS-CoV-2 Vaccination and Post-acute COVID-19 Sequelae
Authors: Gonçalves Bronner P. , Olliaro Piero L. , Horby Peter , Merson Laura , Cowling Benjamin J.
Published: April 2024

This article discusses causal interpretations of epidemiologic studies of the effects of vaccination on sequelae after acute severe acute respiratory syndrome coronavirus 2 infection. To date, researchers have tried to answer several different research questions on this topic. While some studies assessed the impact of postinfection vaccination on the presence of or recovery from post-acute coronavirus disease 2019 syndrome, others quantified the association between preinfection vaccination and postacute sequelae conditional on becoming infected. However, the latter analysis does not have a causal interpretation, except under the principal stratification framework—that is, this comparison can only be interpreted as causal for a nondiscernible stratum of the population. As the epidemiology of coronavirus disease 2019 is now nearly entirely dominated by reinfections, including in vaccinated individuals, and possibly caused by different Omicron subvariants, it has become even more important to design studies on the effects of vaccination on postacute sequelae that address precise causal questions and quantify effects corresponding to implementable interventions.
Precision Medicine for COVID-19 Based on the Inflammatory Response
Authors: Kothalkar Amol D. , Jambhale Dipali , Hingane Vinayak , Gore Satish , Deshpande Sudeep
Published: April 2024

Background

The threat due to the global pandemic of the coronavirus disease 2019 (COVID-19) demands a search for effective treatments to combat the severity of the infections and their associated morbidity and mortality in vulnerable populations. One of the medications with putative antiviral, anti-inflammatory, and immunomodulatory effects is fluvoxamine, a selective serotonin reuptake inhibitor and σ-1 receptor agonist. A few studies have reported doses of 100–300 mg/day to be effective.

Aim

This retrospective study evaluates the outcomes of an individually tailored dosing strategy for fluvoxamine, based on measurements of inflammatory status, in treating COVID-19-positive individuals in India.

Methods

This study included patients with severe acute respiratory syndrome coronavirus 2 infection visiting the outpatient department of a super speciality hospital in India from February to July 2021. Fluvoxamine was initiated at 50 mg or 100 mg twice daily based on their individual C-reactive protein (CRP) and D-dimer status. By day five, patients with rising or static levels of CRP and D-dimer were up-titrated.

Results

In a population of 104 individuals infected with COVID-19, 10 required up-titration of dose, and 94 patients did not need up-titration. Overall, there was very low mortality (N = 1) and hospitalization rate (8.7%). Those individuals who required an up-titration on day five had significantly elevated CRP and D-dimer levels compared to those who were maintained at the initial dose of 50 mg twice daily. In such patients, up-titration of the dose on day 5 appeared to offer better treatment benefits and outcomes. In our study population, there was only one mortality during the course of COVID-19.

Conclusions

Given the individual variability in the host immune response to severe acute respiratory syndrome coronavirus 2 infection, tailoring the dose of a drug such as fluvoxamine based on the inflammatory status of the individual may be beneficial. Individually tailored dosing could combat disease progression while reducing side effects.
A case of uveitis associated with novel corona-virus inactivated vaccine engineered CHO cells: A case report
Authors: Liu Caihui , Zhang Bozhou , Bao Tong , Mudoti Nyasha Grace , Liu Yihan , Zhang Xiaoguang , Yang Yajun , Pang Yunlei
Published: April 2024

Rationale:

The pathogenesis and course of recombinant Corona Virus Disease 2019 vaccine (CHO cell) associated uveitis is rarely seen in clinical practice, thus, it is difficult and time-consuming to diagnose.

Patient concerns:

An adult female patient suffered from binocular visual impairment after receiving the Corona Virus Disease 2019 vaccine. The patient was healthy and had no family history of retinal dystrophy previously. This case showed the following features in multimodal imaging including scattered speckled fluorescein leakage was seen around the optic disc, and the leakage was slightly enhanced in the later stage. The macular area showed about 4 papillary diameter size discoid retinal detachment area fluorescein pool staining. Optical coherence tomography showed retinal choroidal folds above the optic disc, a small amount of fluid under the neuroepithelial layer, and serous detachment of the neuroepithelial layer in the macular area.

Diagnosis:

Posterior uveitis of both eyes.

Intervention:

Orally Maizhiling, Ginkgo biloba leaves, and multivitamins.

Outcome:

After treatment, the symptoms of the patient were significantly improved, and optical coherence tomography reexamination showed exudation had been absorbed.

Lessons:

The injection of a novel coronavirus-inactivated vaccine (CHO cell) can lead to potential uveitis disorders, which is worthy of clinical attention, but the prognosis of patients is good.
Instituting a Palliative Care Trigger in a Surgical Intensive Care Unit (SICU)
Authors: McKay Michelle A. , Mangan Shawn , Fitzpatrick Eleanor , Caplan Holden , Love Gillian , Marks Joshua A. , Liantonio John
Published: April 2024

Increasing palliative care presence in the intensive care unit (ICU) improves symptom management, increases goals-of-care discussion, and reduces unnecessary procedures in ICU patients. An interdisciplinary study team developed a palliative care trigger program in a 17-bed surgical ICU (SICU). Surgical ICU patients who met 3 triggers (ICU length of stay > 10 days, repeat ICU admission, and metastatic cancer) automatically received a palliative care consult. The purpose of the current study was to survey SICU health care professionals before and after the institution of the palliative care trigger program. Overall, the palliative care trigger program was viewed positively by interdisciplinary team members with increased team communication and decreased resistance for the inclusion of palliative care in the SICU plan of care. The palliative care trigger program was successfully developed and implemented in a SICU and was accepted by the interdisciplinary team members caring for SICU patients. Team member feedback is being used to expand the palliative care trigger program to improve care for SICU patients.
Gastric Leiomyosarcoma in Post–Gastrointestinal Stromal Tumor Era: Revisit
Authors: Wang Tengfei , Leng Bing
Published: April 2024

Primary gastric leiomyosarcoma is an exceptionally rare disease. This review covers 41 post-gastrointestinal stromal tumor (GIST) era gastric leiomyosarcoma cases that are supported by immunohistochemistry markers. Other spindle cell lesions are also excluded through histological and immunohistochemistry evaluations. The patients range from 3 to 82 years old, with an average age of 54.6 years. The male-to-female ratio is 1.4:1, from diverse geographic areas. Patients may experience abdominal symptoms, and tumor sizes vary between 1 cm and 22 cm. Morphologically, tumors originate from the muscularis propria or the muscularis mucosae, well-circumscribed with spindle cells arranged in fascicule. Tumoral cells exhibit positivity for smooth muscle markers while being negative for GIST markers and others. The mitotic index ranges from 2 to 500/50 high power field. Ki-67 index varies from 15% to 70%. Management typically involves gastrectomy and other appropriate treatments, with tumor recurrence being uncommon. 56% of patients are alive, with 5 patients dying from this disease. Statistical analyses conducted on post-GIST era cases reveal that a mitotic index of ≥100/50 high power field, tumor recurrence, metastasis, or positive lymph nodes significantly correlate with prognosis.
Differential burden of HIV among adolescent girls and young women by places associated with sex work: an observational study in Mombasa, Kenya
Authors: BECKER Marissa , MISHRA Sharmistha , BHATTACHARJEE Parinita , MUSYOKI Helgar , TENNAKOON Aruni , LEUNG Stella , CHEUK Eve , LORWAY Rob , ISAC Shajy , MA Huiting , CHOLETTE Francois , SANDSTROM Paul , GICHANGI Peter , MWATELAH Ruth , MCKINNON Lyle , BLANCHARD James , PICKLES Michael ,   the Transitions Study Team
Published: April 2024

Background:

The design of HIV prevention programs for adolescent girls and young women (AGYW) are informed by data on who is at highest risk, and where they can be reached. Places (hotspots) associated with selling sex are an established outreach strategy for sex work programs, but could be used to reach other AGYW at high risk.

Setting:

This study took place in Mombasa, Kenya.

Methods:

We conducted a cross-sectional, bio-behavioural survey among (N=1,193) sexually active AGYW aged 14-24 years recruited at hotspots. We compared HIV prevalence by sub-group (sex work, SW; transactional sex, TS; and non-transactional sex, NTS), stratified by hotspot type (venues and non-venues). We examined whether associations between HIV prevalence and hotspot/subgroup remained after adjustment for individual-level risk factors, and estimated HIV prevalence ratio (PR) with and without adjustment for these individual-level factors.

Results:

Overall HIV prevalence was 5.6%, 5.3% in venues and 7.3% in non-venues. Overall SW HIV prevalence was two-fold higher than among participants engaged in NTS. After adjusting for age and individual-level risk factors, HIV prevalence was 2.72 times higher among venue-based SWs (95% CI: 1.56-4.85) and 2.11 times higher among non-venue AGYW not engaged in SW (95% CI: 0.97-4.30) compared to venue-based AGYW not engaged in SW.

Conclusion:

AGYW who sell sex remain at high risk of HIV across types of hotspots. The residual pattern of elevated HIV burden by AGWY subgroup and hotspot type suggests that unmeasured, network-level factors underscore differential risks. As such, hotspots constitute a “place” to reach AGYW at high risk of HIV.
High-Specific-Activity 131I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma
Authors: Al-Ward Ruaa , Brondani Vania Balderrama , Sawani Sahar , Potter Cheryl L. , Xu Guofan , Waguespack Steven G. , Varghese Jeena , Habra Mouhammed Amir , Lu Yang , Jimenez Camilo
Published: April 2024

Background

Metastatic pheochromocytomas and paragangliomas (MPPGLs) are rare tumors with limited treatment options. High-specific-activity 131I-MIBG (HSA-131I-MIBG) is the only US Food and Drug Administration–approved therapy for MPPGL. We studied the efficacy and safety of HSA-131I-MIBG in routine clinical practice.

Patients and Methods

The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background.

Results

The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6–25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease (SDHB, VHL, RET); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.

The most common adverse events were grades 1–2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3–4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis.

Conclusions

HSA-131I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.
Chemokine Receptor 4–Targeted PET/CT With 68Ga-Pentixather Detects More Lesions Than 68Ga-Pentixafor PET/CT in Multiple Myeloma
Authors: Yang Qiao , Zhang Fujing , Hao Zhixin , Zhuang Junling , Huo Li
Published: April 2024

An 83-year-old woman with newly diagnosed multiple myeloma (MM) was enrolled in our 68Ga-pentixather and 68Ga-pentixafor PET/CT trial for evaluation of tumor burden. 68Ga-pentixather PET/CT detected more focal bone lesions, and the uptake levels of focal bone lesions on 68Ga-pentixather PET/CT were higher than those on 68Ga-pentixafor PET/CT. This suggests that 68Ga-pentixather PET/CT may be an alternative imaging modality and more sensitive in detecting MM lesions than 68Ga-pentixafor PET/CT.
Planning Angiography for 90Y-Radioembolization Demonstrates a Variety of Unusual Extrahepatic Perfusion Patterns
Authors: Benson Andrea , Koo Sonya J. , Berman Zachary
Published: April 2024

In preparation for 90Y radioembolization for hepatic malignancies, hepatic angiography is performed with intra-arterial delivery of 99mTc-macroaggregated albumin (MAA), known as premapping. This initial procedure allows for evaluation of standard/variant hepatic arterial anatomy using MAA as a surrogate marker for the delivery of 90Y to visualize the likely distribution of 90Y. Premapping allows for the assessment of at-risk extrahepatic targets and for the quantification of hepatopulmonary shunting. We present cases where MAA scintigraphic images reveal unusual perfusion patterns in hepatic cancers, treated with 90Y glass microspheres (Therasphere; Boston Scientific, Marlborough, MA).
Scheduled Follow-Up and Association with Emergency Department Use and Readmission after Trauma
Authors: Smith Sophia M , Zhao Xuewei , Kenzik Kelly , Michael Cara , Jenkins Kendall , Sanchez Sabrina E
Published: April 2024

BACKGROUND:

After traumatic injury, 13% to 14% of patients use the emergency department (ED) and 11% are readmitted within 30 days. Decreasing ED visits and readmission represents a target for quality improvement. This cohort study evaluates risk factors for ED visits and readmission after trauma, focusing on outpatient follow-up.

STUDY DESIGN:

We conducted a retrospective chart review of adult trauma admissions from January 1, 2018, to December 31, 2021. Our primary exposure was outpatient follow-up, primary outcome was ED use, and secondary outcome was readmission. Multivariable logistic regression evaluated the association between primary exposure and outcomes, adjusting for factors identified on unadjusted analysis.

RESULTS:

In total, 2,266 patients met inclusion criteria, with an 11.3% ED visit rate and 4.1% readmission rate. Attending follow-up did not have a significant association with ED visit (odds ratio 0.99, 95% CI 0.99 to 2.01, p = 0.05) or readmission rate (odds ratio 1.68, 95% CI 0.95 to 2.99, p = 0.08). Significant associations with ED use included non-White race, depression, anxiety, substance use disorder, discharge disposition, and being discharged with lines or drains. Significant associations with readmission included depression, anxiety, and discharge disposition.

CONCLUSIONS:

Emphasizing outpatient follow-up in trauma patients is not an effective target to decrease ED use or readmission. Future studies should focus on supporting patients with mental health comorbidities and investigating interventions to optimally engage with trauma patients after hospital discharge.
Cable bacteria delay euxinia and modulate phosphorus release in coastal hypoxic systems
Authors: Burdorf Laurine D. W. , van de Velde Sebastiaan J. , Hidalgo-Martinez Silvia , Meysman Filip J. R.
Published: April 2024

Cable bacteria are long, filamentous bacteria with a unique metabolism involving centimetre-scale electron transport. They are widespread in the sediment of seasonally hypoxic systems and their metabolic activity stimulates the dissolution of iron sulfides (FeS), releasing large quantities of ferrous iron (Fe
2+
) into the pore water. Upon contact with oxygen, Fe
2+
oxidation forms a layer of iron(oxyhydr)oxides (FeO
x
), which in its turn can oxidize free sulfide (H
2
S) and trap phosphorus (P) diffusing upward. The metabolism of cable bacteria could thus prevent the release of H
2
S from the sediment and reduce the risk of euxinia, while at the same time modulating P release over seasonal timescales. However, experimental support for this so-called ‘iron firewall hypothesis’ is scarce. Here, we collected natural sediment in a seasonally hypoxic basin in three different seasons. Undisturbed sediment cores were incubated under anoxic conditions and the effluxes of H
2
S, dissolved iron (dFe) and phosphate (PO
4
3−
) were monitored for up to 140 days. Cores with recent cable bacterial activity revealed a high stock of sedimentary FeO
x
, which delayed the efflux of H
2
S for up to 102 days. Our results demonstrate that the iron firewall mechanism could exert an important control on the prevalence of euxinia and regulate the P release in coastal oceans.
A shared pattern of midfacial bone modelling in hominids suggests deep evolutionary roots for human facial morphogenesis
Authors: Schuh Alexandra , Heuzé Yann , Gunz Philipp , Berthaume Michael A. , Shaw Colin N. , Hublin Jean-Jacques , Freidline Sarah
Published: April 2024

Midfacial morphology varies between hominoids, in particular between great apes and humans for which the face is small and retracted. The underlying developmental processes for these morphological differences are still largely unknown. Here, we investigate the cellular mechanism of maxillary development (bone modelling, BM), and how potential changes in this process may have shaped facial evolution. We analysed cross-sectional developmental series of gibbons, orangutans, gorillas, chimpanzees and present-day humans (
n
= 183). Individuals were organized into five age groups according to their dental development. To visualize each species's BM pattern and corresponding morphology during ontogeny, maps based on microscopic data were mapped onto species-specific age group average shapes obtained using geometric morphometrics. The amount of bone resorption was quantified and compared between species. Great apes share a highly similar BM pattern, whereas gibbons have a distinctive resorption pattern. This suggests a change in cellular activity on the hominid branch. Humans possess most of the great ape pattern, but bone resorption is high in the canine area from birth on, suggesting a key role of canine reduction in facial evolution. We also observed that humans have high levels of bone resorption during childhood, a feature not shared with other apes.
Sex-specific transgenerational effects of diet on offspring life history and physiology
Authors: Camilleri Tara-Lyn , Piper Matthew D. W. , Robker Rebecca L. , Dowling Damian K.
Published: April 2024

Dietary variation in males and females can shape the expression of offspring life histories and physiology. However, the relative contributions of maternal and paternal dietary variation to phenotypic expression of latter generations is currently unknown. We provided male and female
Drosophila melanogaster
grandparents with diets differing in sucrose concentration prior to reproduction, and similarly subjected their grandoffspring to the same treatments. We then investigated the phenotypic consequences of this dietary variation among the grandsons and granddaughters. We observed transgenerational effects of dietary sucrose, mediated through the grandmaternal lineage, which mimic the direct effects of sucrose on lifespan, with opposing patterns across sexes; low sucrose increased female, but decreased male, lifespan. Dietary mismatching of grandoffspring–grandparent diets increased lifespan and reproductive success, and moderated triglyceride levels of grandoffspring, providing insights into the physiological underpinnings of the complex transgenerational effects on life histories.
The impact of within-host coinfection interactions on between-host parasite transmission dynamics varies with spatial scale
Authors: Keegan Shaun P. , Pedersen Amy B. , Fenton Andy
Published: April 2024

Within-host interactions among coinfecting parasites can have major consequences for individual infection risk and disease severity. However, the impact of these within-host interactions on between-host parasite transmission, and the spatial scales over which they occur, remain unknown. We developed and apply a novel spatially explicit analysis to parasite infection data from a wild wood mouse (
Apodemus sylvaticus
) population. We previously demonstrated a strong within-host negative interaction between two wood mouse gastrointestinal parasites, the nematode
Heligmosomoides polygyrus
and the coccidian
Eimeria hungaryensis
, using drug-treatment experiments. Here, we show this negative within-host interaction can significantly alter the between-host transmission dynamics of
E. hungaryensis
, but only within spatially restricted neighbourhoods around each host. However, for the closely related species
E. apionodes
, which experiments show does not interact strongly with
H. polygyrus
, we did not find any effect on transmission over any spatial scale. Our results demonstrate that the effects of within-host coinfection interactions can ripple out beyond each host to alter the transmission dynamics of the parasites, but only over local scales that likely reflect the spatial dimension of transmission. Hence there may be knock-on consequences of drug treatments impacting the transmission of non-target parasites, altering infection risks even for non-treated individuals in the wider neighbourhood.
Vertically inherited microbiota and environment modifying behaviours conceal genetic variation in dung beetle life history
Authors: Rohner Patrick T. , Moczek Armin P.
Published: April 2024

Diverse organisms actively manipulate their (sym)biotic and physical environment in ways that feed back on their own development. However, the degree to which these processes affect microevolution remains poorly understood. The gazelle dung beetle both physically modifies its ontogenetic environment and structures its biotic interactions through vertical symbiont transmission. By experimentally eliminating (i) physical environmental modifications and (ii) the vertical inheritance of microbes, we assess how environment modifying behaviour and microbiome transmission shape heritable variation and evolutionary potential. We found that depriving larvae of symbionts and environment modifying behaviours increased additive genetic variance and heritability for development time but not body size. This suggests that larvae's ability to manipulate their environment has the potential to modify heritable variation and to facilitate the accumulation of cryptic genetic variation. This cryptic variation may become released and selectable when organisms encounter environments that are less amenable to organismal manipulation or restructuring. Our findings also suggest that intact microbiomes, which are commonly thought to increase genetic variation of their hosts, may instead reduce and conceal heritable variation. More broadly, our findings highlight that the ability of organisms to actively manipulate their environment may affect the potential of populations to evolve when encountering novel, stressful conditions.
Inferring the evolution of reproductive isolation in a lineage of fossil threespine stickleback,
Gasterosteus doryssus
Authors: Siddiqui Raheyma , Swank Samantha , Ozark Allison , Joaquin Franklin , Travis Matthew P. , McMahan Caleb D. , Bell Michael A. , Stuart Yoel E.
Published: April 2024

Darwin attributed the absence of species transitions in the fossil record to his hypothesis that speciation occurs within isolated habitat patches too geographically restricted to be captured by fossil sequences. Mayr's peripatric speciation model added that such speciation would be rapid, further explaining missing evidence of diversification. Indeed, Eldredge and Gould's original punctuated equilibrium model combined Darwin's conjecture, Mayr's model and 124 years of unsuccessfully sampling the fossil record for transitions. Observing such divergence, however, could illustrate the tempo and mode of evolution during early speciation. Here, we investigate peripatric divergence in a Miocene stickleback fish,
Gasterosteus doryssus.
This lineage appeared and, over approximately 8000 generations, evolved significant reduction of 12 of 16 traits related to armour, swimming and diet, relative to its ancestral population. This was greater morphological divergence than we observed between reproductively isolated, benthic-limnetic ecotypes of extant
Gasterosteus aculeatus
. Therefore, we infer that reproductive isolation was evolving
.
However, local extinction of
G. doryssus
lineages shows how young, isolated, speciating populations often disappear, supporting Darwin's explanation for missing evidence and revealing a mechanism behind morphological stasis. Extinction may also account for limited sustained divergence within the stickleback species complex and help reconcile speciation rate variation observed across time scales.
Combining transinfected
Wolbachia
and a genetic sexing strain to control
Aedes albopictus
in laboratory-controlled conditions
Authors: Scussel Sarah , Gaudillat Benjamin , Esnault Jérémy , Lejarre Quentin , Duployer Marianne , Lebon Cyrille , Benlali Aude , Mavingui Patrick , Tortosa Pablo , Cattel Julien
Published: April 2024

The global expansion of
Aedes albopictus
has stimulated the development of environmentally friendly methods aiming to control disease transmission through the suppression of natural vector populations. Sterile male release programmes are currently being deployed worldwide, and are challenged by the availability of an efficient sex separation which can be achieved mechanically at the pupal stage and/or by artificial intelligence at the adult stage, or through genetic sexing, which allows separating males and females at an early development stage. In this study, we combined the genetic sexing strain previously established based on the linkage of dieldrin resistance to the male locus with a
Wolbachia
transinfected line. For this, we introduced either the
w
Pip-I or the
w
Pip-IV strain from
Culex pipiens
in an asymbiotic
Wolbachia
-free
Ae
.
albopictus
line. We then measured the penetrance of cytoplasmic incompatibility and life-history traits of both transinfected lines, selected the
w
Pip-IV line and combined it with the genetic sexing strain. Population suppression experiments demonstrated a 90% reduction in population size and a 50% decrease in hatching rate. Presented results showed that such a combination has a high potential in terms of vector control but also highlighted associated fitness costs, which should be reduced before large-scale field assay.