bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimates of Crystallinity Utilizing Differential Scanning Calorimetry: Application to the Kīlauea 2018 Lower East Rift Zone Eruption
Authors: Halverson B A , Emerson A , Hammer J , Lira J , Whittington A
Published: February 2024

Rocks produced by diverse processes, from condensation in space to impacts on planetary surfaces to volcanism, contain both crystals and amorphous material. Crystallinity provides information on the thermal history of the sample and is especially important in characterizing volcanic rocks and pyroclasts because lava rheology is profoundly influenced by the crystal content. Crystallinity is typically quantified via microscopy, using transmitted light or backscattered electrons. However, many samples present visibly ambiguous textures such as intimate intergrowth of crystal phases, and/or crystal sizes extending down to the nanometer scale. Here, we apply calorimetric methods involving heat capacity and enthalpy to assess the crystallinity of a series of volcanic samples. We tested three different approaches, using differential scanning calorimetry, on 30–40 mg aliquots of powdered basalts from the 2018 Kīlauea lower East Rift Zone. The first approach involves determining the magnitude of the increase in heat capacity at the glass transition, which can determine crystallinity to a 1σ precision of ±3%. The second approach is based on the enthalpy of fusion, which requires a longer more complex procedure with results that are typically more uncertain than for the heat capacity method, with a 1σ of ±6%. A final method utilizing differences in enthalpies calculated from the heat capacities required the most complex procedure and has the greatest uncertainty of ±18%. Preliminary results for lavas with microscopically determined crystallinities ranging from 11 to 98% indicate that crystallinity based on calorimetric data can be tens of percent higher than the average value identified using microscopy and petrographic analysis. Image-based methodologies applied to sections of samples reveal spatial heterogeneity and details in texture and crystallinity, whereas calorimetry-based methodologies capture the overall ‘bulk sample’ properties, unbiased by section effects or imaging resolution limits. These techniques are a powerful combination that can present complementary views of crystallinity.
Policing a neurodiverse world: Lessons from the social model of disability
Authors: Thacher David
Published: February 2024

Programs that aim to improve the police response to mental health crises and related incidents have implicitly relied on a medical/individual model of psychiatric disability, which emphasizes efforts to provide mental health treatments to individuals. This paper argues that this perspective has unnecessarily limited the range of options that police might draw from to manage these incidents. Advocates of an alternative, social model of psychiatric disability (as well as the “neurodiversity paradigm” it inspired) argue that we should view disability not as a property of individuals with certain impairments but as a property of the society that has failed to accommodate them. I argue that repeated calls to the police provide important information about the location and character of those failures, and that police have an important role to play in rectifying them. I illustrate how police have already played that role in several cities.
Interactive computational and experimental approaches improve the sensitivity of periplasmic binding protein-based nicotine biosensors for measurements in biofluids
Authors: Haloi Nandan , Huang Shan , Nichols Aaron L , Fine Eve J , Friesenhahn Nicholas J , Marotta Christopher B , Dougherty Dennis A , Lindahl Erik , Howard Rebecca J , Mayo Stephen L , Lester Henry A
Published: February 2024

We developed fluorescent protein sensors for nicotine with improved sensitivity. For iNicSnFR12 at pH 7.4, the proportionality constant for ∆F/F0vs [nicotine] (δ-slope, 2.7 μM−1) is 6.1-fold higher than the previously reported iNicSnFR3a. The activated state of iNicSnFR12 has a fluorescence quantum yield of at least 0.6. We measured similar dose-response relations for the nicotine-induced absorbance increase and fluorescence increase, suggesting that the absorbance increase leads to the fluorescence increase via the previously described nicotine-induced conformational change, the ‘candle snuffer’ mechanism. Molecular dynamics (MD) simulations identified a binding pose for nicotine, previously indeterminate from experimental data. MD simulations also showed that Helix 4 of the periplasmic binding protein (PBP) domain appears tilted in iNicSnFR12 relative to iNicSnFR3a, likely altering allosteric network(s) that link the ligand binding site to the fluorophore. In thermal melt experiments, nicotine stabilized the PBP of the tested iNicSnFR variants. iNicSnFR12 resolved nicotine in diluted mouse and human serum at 100 nM, the peak [nicotine] that occurs during smoking or vaping, and possibly at the decreasing levels during intervals between sessions. NicSnFR12 was also partially activated by unidentified endogenous ligand(s) in biofluids. Improved iNicSnFR12 variants could become the molecular sensors in continuous nicotine monitors for animal and human biofluids.
Long non-coding RNA H19X as a regulator of mononuclear cell adhesion to the endothelium in systemic sclerosis
Authors: Tirelli Francesca , Pachera Elena , Gmür Sabrina , Lafyatis Robert , Huang Mengqi , Zulian Francesco , Camarillo Retamosa Eva , Kania Gabriela , Distler Oliver
Published: February 2024

Objective

To define the functional relevance of H19 X-linked (H19X) co-expressed long non-coding RNA (lncRNA) in endothelial cell (EC) activation as a key process in SSc vasculopathy.

Methods

H19X expression in SSc skin biopsies was analysed from single-cell RNA sequencing (scRNA-seq) data. Differential expression and pathway enrichment analysis between cells expressing (H19Xpos) and non-expressing H19X (H19Xneg) cells was performed. H19X function was investigated in human dermal microvascular ECs (HDMECs) by silencing. H19X and EC adhesion molecule levels were analysed by real-time quantitative PCR and western blot after stimulation with pro-inflammatory cytokines. Cytoskeletal rearrangements were analysed by fluorescent staining. Endothelial adhesion was evaluated by co-culture of HDMECs and fluorescent-labelled peripheral blood mononuclear cells (PBMCs). Shedding vascular cell adhesion protein 1 (VCAM1) was evaluated by ELISA on HDMEC supernatant.

Results

The scRNA-seq data showed significant upregulation of H19X in SSc compared with healthy ECs. In HDMECs, H19X was consistently induced by IFN type I and II. H19X knockdown lead to a significant decrease in the mRNA of several adhesion molecules. In particular, VCAM1 was significantly reduced at the protein and mRNA levels. Co-expression analysis of the scRNA-seq data confirmed higher expression of VCAM1 in H19Xpos ECs. ECs were also strongly associated with the ‘cell adhesion molecule’ pathway. Moreover, the VCAM1 downstream pathway displayed less activation following H19X knockdown. Contractility of HDMECs, PBMC adhesion to HDMECs and VCAM1 shedding were also reduced following H19X knockdown.

Conclusions

lncRNA H19X may contribute to EC activation in SSc vasculopathy, acting as a regulator of expression of adhesion molecules in ECs.
Augmented Fixation in Transverse Midshaft Humerus Fractures Using a Nitinol Staple: Surgical Technique and Case Series
Authors: Graham Jack G. , Davis Daniel E.
Published: February 2024

Maintaining the reduction of a transverse humeral shaft fracture can be particularly challenging while applying a compression plate for definitive fixation. Nitinol compression staples are being increasingly utilized in orthopedic surgery due to their unique ability to apply continuous compression between staple legs at body temperature. We have found them to be particularly useful in the maintenance of the reduction of transverse humeral shaft fractures before compression plate application. This simple technique allows for the removal of reduction clamps and precise plate placement. We describe our technique for using nitinol compression staples to augment fracture fixation in transverse humeral shaft fractures as well as our experience using this technique in a case series of 4 patients.
Management of Hypertension in Patients With Polycystic Ovarian Syndrome: A Mini-Review
Authors: Liaghatdar Amin , Mazaheri-Tehrani Sadegh , Fakhrolmobasheri Mohammad
Published: February 2024

Polycystic ovarian syndrome (PCOS) is a common problem among young women. It is characterized mainly by hyperandrogenism features, such as hirsutism, menstrual problems, and anovulation. Diagnosis is based on the existence of 2 items out of, oligo-ovulation, hyperandrogenism features, and ultrasounds findings. Cardiovascular complications such as hypertension are a prevalent serious condition in these patients which is mainly predisposed by the high levels of androgens, and insulin resistance. High blood pressure should be controlled well to prevent the progression of other serious conditions. Various antihypertensive drugs could be prescribed. However, in selecting an antihypertensive medication, other therapeutic properties of the drug should also be considered. Up to now, many clinicians do not differ between PCOS patients with hypertension and other hypertensive patients. However, being aware of the potential effects of each hypertension drug could help to choose better options for the patient. Here is a brief review of how each antihypertensive drug could affect PCOS women and if they cause any improvement in the disorder progression.
Process and Outcomes of Fitting Corneoscleral Profilometry-Driven Scleral Lenses for Patients With Ocular Surface Disease
Authors: Yoon Hannah , Harthan Jennifer S. , Skoog William , Fogt Jennifer S. , Nau Amy , Nau Cherie B. , Schornack Muriel , Shorter Ellen
Published: February 2024

Objectives:

To assess the feasibility of obtaining cornea scleral profile (CSP) measurements using Scheimpflug imaging and report on the fitting process of free-form custom scleral lenses (SLs) for patients with ocular surface disease (OSD).

Methods:

This prospective study of patients fit with free-form SLs collected data on the following: demographics, indications for wear, corneal and scleral tomography, scan acquisition process, and SL fitting process.

Results:

Cornea scleral profile scans were acquired on 15 eyes of nine patients. Mean scan time for right eyes was 10.7, and 9.7 min for left eyes. A mean of 2.9 follow-up visits were required to complete SL fitting, with a mean of 2.1 lenses ordered. One eye did not tolerate lens wear, and one eye could not be fit using the CSP scan because of insufficient data. The initial lens ordered was dispensed at the first follow-up visit for seven of the remaining 13 eyes, all of which were ultimately fit successfully in free-form lenses.

Conclusions:

In this study of profilometry-guided SL fitting for eyes with OSD and low magnitude corneal astigmatism, the number of lenses and follow-up visits required were similar to outcomes of previous studies that described the diagnostic approach to SL fitting. In addition, imaging technology does not negate the need for skilled clinical observation while fitting SLs.
Structure-based approaches against COVID-19
Authors: Huang Ta-Chou , Liang Kung-Hao , Chang Tai-Jay , Hung Kai-Feng , Wang Mong-Lien , Cheng Yen-Fu , Liao Yi-Ting , Yang De-Ming
Published: February 2024

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on human life. This review highlights the versatile roles of both classical and modern structure-based approaches for COVID-19. X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryogenic electron microscopy are the three cornerstones of classical structural biology. These technologies have helped provide fundamental and detailed knowledge regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the related human host proteins as well as enabled the identification of its target sites, facilitating the cessation of its transmission. Further progress into protein structure modeling was made using modern structure-based approaches derived from homology modeling and integrated with artificial intelligence (AI), facilitating advanced computational simulation tools to actively guide the design of new vaccines and the development of anti-SARS-CoV-2 drugs. This review presents the practical contributions and future directions of structure-based approaches for COVID-19.
Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber hereditary optic neuropathy in vitro
Authors: Yang Yi-Ping , Chang Yuh-Lih , Chiou Guang-Yuh , Lee Meng-Shiue , Wu You-Ren , Chen Po-Wei , Lin Yi-Ying , Lai Wei-Yi , Liu Yu-Hao , Hwang De-Kuang , Chien Yueh
Published: February 2024

Background:

Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis and reactive oxygen species (ROS) levels, which is accepted to be caused by the mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. Unaffected carrier carries LHON mutation but shows normal phenotype, suggesting that the disease’s pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction.

Methods:

Using LHON patient-specific induced pluripotent stem cells (iPSCs) as the in vitro disease model, we previously demonstrated that circRNA_0087207 had the most significantly higher expression level in the LHON patient-iPSC-derived RGCs compared with the unaffected carrier-iPSC-derived RGCs. To elaborate the underlying pathologies regulated by circRNA_008720 mechanistically, bioinformatics analysis was conducted and elucidated that circRNA_0087207 could act as a sponge of miR-548c-3p and modulate PLSCR1/TGFB2 levels in ND4 mutation-carrying LHON patient-iPSC-derived RGCs.

Results:

Using LHON iPSC-derived RGCs as the disease-based platform, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on targeted mRNA of miR-548c-3p showed the connection with apoptosis, suggesting downregulation of miR548c-3p contributes to the apoptosis of LHON patient RGCs.

Conclusion:

We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.
Performance of GPT-4 and GPT-3.5 in generating accurate and comprehensive diagnoses across medical subspecialties
Authors: Luk Dik Wai Anderson , Ip Whitney Chin Tung , Shea Yat-fung
Published: February 2024

Artificial intelligence has demonstrated a promising potential for diagnosing complex medical cases, with Generative Pre-Trained Transformer 4 (GPT-4) being the most recent advancement in this field. This study evaluated the diagnostic performance of the GPT-4 in comparison with that of its predecessor, GPT-3.5, using 81 complex medical case records from the New England Journal of Medicine. The cases were categorized as cognitive impairment, infectious disease, rheumatology, or drug reactions. The GPT-4 achieved a primary diagnostic accuracy of 38.3%, which improved to 71.6% when differential diagnoses were included. In 84.0% of cases, primary diagnoses were made by conducting investigations suggested by GPT-4. GPT-4 outperformed GPT-3.5 in all subspecialties except for drug reactions. GPT-4 demonstrated the highest performance in infectious diseases and drug reactions, whereas it underperformed in cases of cognitive impairment. These findings indicate that GPT-4 can provide reasonably accurate diagnoses, comprehensive differential diagnoses, and appropriate investigations. However, its performance varies across subspecialties.
Policy Challenges and Resiliency Related to Ending the HIV Epidemic in the Southern and Rural United States: A Call to Action
Authors: Moen Marik , Sublette Nina , Alves Justin , Walker Crystal Martin
Published: February 2024

In this commentary, we describe current policy trends and their implications for the health of populations in the Southern and rural United States. We outline policy changes that threaten the prevention, care, and treatment of people at risk for HIV or with HIV and sociopolitical factors contributing to these policy trends. We also issue a call-to-action for individuals with Southern and rural US policy expertise and lived or living experience to collaboratively engage on a systematic policy analysis to thoroughly document relevant policies and deepen our understanding of the influences behind these policies. Finally, we provide examples of individual, community, and national level resiliency and courage—strategies that inspire advocacy and hope in the face of policy setbacks.
Cluster Analysis of World Trade Center Related Lower Airway Diseases
Authors: de la Hoz Rafael E. , Jeon Yunho , Doucette John T. , Reeves Anthony P. , San José Estépar Raúl , Celedón Juan C.
Published: February 2024

Introduction: Cluster analysis can classify without a priori assumptions the heterogeneous chronic lower airway diseases found in former workers at the World Trade Center (WTC) disaster site. Methods: We selected the first available chest computed tomography scan with quantitative computed tomography measurements on 311 former WTC workers with complete clinical, and spirometric data from their closest surveillance visit. We performed a nonhierarchical iterative algorithm K-prototype cluster analysis, using gap measure. Results: A five-cluster solution was most satisfactory. Cluster 5 had the healthiest individuals. In cluster 4, smoking was most prevalent and intense but there was scant evidence of respiratory disease. Cluster 3 had symptomatic subjects with reduced forced vital capacity impairment (low FVC). Clusters 1 and 2 had less dyspneic subjects, but more functional and quantitative computed tomography evidence of chronic obstructive pulmonary disease (COPD) in cluster 1, or low FVC in cluster 2. Clusters 1 and 4 had the highest proportion of rapid first-second forced expiratory volume decliners. Conclusions: Cluster analysis confirms low FVC and COPD/pre-COPD as distinctive chronic lower airway disease phenotypes on long-term surveillance of the WTC workers.
The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy
Authors: Duque Patricia , Perez-Peña Jose María , Alarcon-Perez Lleimi , Olmedilla Luis , Varela Jesús Alberto , Pascual Cristina , Rodriguez-Huerta Ana María , Asencio José Manuel , Lopez-Baena Jose Ángel , Garutti Ignacio
Published: February 2024

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function (P < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival (P < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.
Associated factors of depression in primiparas with hypothyroidism during pregnancy
Authors: Wang Dan , Huang Cui-Qin , Jiang Rong-Zhen , Fan Ya-Jing
Published: February 2024

This cross-sectional study aimed to explore the associated factors of depression in primiparas with hypothyroidism during pregnancy. The research subjects were 200 primiparas with hypothyroidism during pregnancy who were admitted to our hospital between December 2016 and December 2019. Self-rating depression scale scores were used to evaluate the depression, and the incidence of depression were examined. The data from all the subjects were collected to compare the differences between primiparas with hypothyroidism during pregnancy with and without depression. A logistic regression equation was used to analyze the influencing factors of depression in these patients. Of the 200 primiparas who took part in this study, 27 suffered from depression, accounting for 13.50%. There were differences in age, education level, economic income, sleep quality, and conjugal relations between the depressed and the nondepressed participants. When the above factors were included in the logistic regression equation, it was found that the odds ratio values for these factors were all >1, which indicated that they had an influence on maternal depression in primiparas with hypothyroidism during pregnancy. This study demonstrated that pregnancy-associated hypothyroidism in primiparas is affected by age, education level, economic income, sleep quality, and conjugal relations, all of which increase the incidence of depression. Relevant preventive measures should be provided in clinical practice to avoid the occurrence of depression.
The correlation between gut microbiota and both neurotransmitters and mental disorders: A narrative review
Authors: Mhanna Amjad , Martini Nafiza , Hmaydoosh Ghefar , Hamwi George , Jarjanazi Mulham , Zaifah Ghaith , Kazzazo Reem , Haji Mohamad Aya , Alshehabi Zuheir
Published: February 2024

The gastrointestinal tract is embedded with microorganisms of numerous genera, referred to as gut microbiota. Gut microbiota has multiple effects on many body organs, including the brain. There is a bidirectional connection between the gut and brain called the gut-brain-axis, and these connections are formed through immunological, neuronal, and neuroendocrine pathways. In addition, gut microbiota modulates the synthesis and functioning of neurotransmitters. Therefore, the disruption of the gut microbiota in the composition or function, which is known as dysbiosis, is associated with the pathogenesis of many mental disorders, such as schizophrenia, depression, and other psychiatric disorders. This review aims to summarize the modulation role of the gut microbiota in 4 prominent neurotransmitters (tryptophan and serotonergic system, dopamine, gamma-aminobutyric acid, and glutamate), as well as its association with 4 psychiatric disorders (schizophrenia, depression, anxiety disorders, and autism spectrum disorder). More future research is required to develop efficient gut-microbiota-based therapies for these illnesses.
A case report: intravenous leiomyomatosis extending from the uterus to the right atrium
Authors: Ziani Hicham , El Idrissi Jallal Nora , Lahbabi Yassir , Slaihi Zakariae , Lahbabi Sophia , Oudghiri Nezha , Tachinante Rajae
Published: February 2024

Introduction and importance:

Intra veinous leiomyomatosis (IVL) is one pathology of a known group of ectopic leiomyomatosis that gathers many entities all defined by the presence of benign tumours arising from uterine smooth muscle cells. The authors aim through this case report to address the underdiagnosis of IVL in pre-menopausal women and the potential confusion with other cardiac tumours.

Case presentation:

A 48-year-old woman initially treated for a suspected intracardiac myxoma underwent two surgeries. Seeking gynaecological care for menometrorrhagia related to a polymyomatous uterus, she was scheduled for radical surgery. Unexpectedly, extended explorations during a hysterectomy revealed a tumour originating from the pelvis, extending to the right atrium and inferior vena cava, indicative of intravascular leiomyomatosis.

Clinical discussion:

IVL’s diagnosis is often incidental during hysterectomy analysis, with symptoms mimicking uterine fibroids. Treatment involves radical surgery, emphasizing the importance of complete resection to reduce the significant risk of recurrence.

Conclusion:

Pre-menopausal women with a history of hysterectomy or myomectomy and a detected right chamber mass should be screened for intravascular leiomyomatosis. Diagnosis relies on histological examination, guiding tailored treatment choices such as surgical resection with a focus on bilateral adnexectomy for optimal outcomes.
A Case of Varicella Zoster and Mpox Coinfection in a Patient Living With HIV
Authors: Mazumder Archisman , Lim Lindsay , White Cameron M. , Van Gerwen Olivia T.
Published: February 2024

We present a case of recurrent, cutaneous mpox with coinfection of disseminated varicella zoster in an immunocompromised patient with poorly controlled HIV. This case demonstrates the importance of maintaining a high index of suspicion for mpox despite prior infection and vaccination, as suboptimal immune response is possible in immunocompromised patients, and also noting the potential for coinfection necessitating timely diagnosis and appropriate testing.
Assessing the Impact of COVID-19 on HIV Outcomes in the United States: A Modeling Study
Authors: Viguerie Alex , Jacobson Evin U. , Hicks Katherine A. , Bates Laurel , Carrico Justin , Honeycutt Amanda , Lyles Cindy , Farnham Paul G.
Published: February 2024

Background

The COVID-19 pandemic impacted sexual behaviors and the HIV continuum of care in the United States, reducing HIV testing and diagnosis, and use of preexposure prophylaxis and antiretroviral therapy. We aimed to understand the future implications of these effects through a modeling study.

Methods

We first ran our compartmental model of HIV transmission in the United States accounting for pandemic-related short-term changes in transmission behavior and HIV prevention and care provision in 2020 to 2021 only. We then ran a comparison scenario that did not apply pandemic effects but assumed a continuation of past HIV prevention and care trends. We compared results from the 2 scenarios through 2024.

Results

HIV incidence was 4·4% lower in 2020 to 2021 for the pandemic scenario compared with the no-pandemic scenario because of reduced levels of transmission behavior, despite reductions in HIV prevention and care caused by the pandemic. However, reduced care led to less viral load suppression among people with HIV in 2020, and in turn, our model resulted in a slightly greater incidence of 2·0% from 2022 to 2024 in the COVID-19 scenario, as compared with the non-COVID scenario.

Discussion

Disruptions in HIV prevention and care services during COVID-19 may lead to somewhat higher postpandemic HIV incidence than assuming prepandemic trends in HIV care and prevention continued. These results underscore the importance of continuing to increase HIV prevention and care efforts in the coming years.
Implementation of Point of Care Sexually Transmitted Infections Testing in a Community Clinic Setting
Authors: Toma Emily , Malyuta Yelena , Salhaney Peter , Nunn Amy , Maynard Michaela , Tao Jun , Sutten Coats Cassie , Chan Philip A.
Published: February 2024

The rates of sexually transmitted infections (STIs) in the United States, including chlamydia and gonorrhea, are rising. Point-of-care (POC) testing could increase access to testing and treatment. This evaluation found POC STI testing to be concordant with the results of traditional laboratory testing for 100% of patients who were tested. Ninety-five percent of the patients reported being satisfied with the experience, and 66% preferred it to traditional laboratory testing. The most commonly reported reason for preferring the test was the short amount of time it took to receive results. However, insurance reimbursed less than 30% of what was billed for the POC tests. Low insurance reimbursement rates could be a barrier to implementation long-term financial sustainability of POC STI testing.
Al18F-NOTA-Octreotide PET/CT and 18F-FDG PET/CT for Detecting Cerebellar Hemangioblastoma in a Patient With Von Hippel-Lindau Disease
Authors: Hou Guozhu , Cheng Xin , Chi Yihebali , Wang Xuejuan , Zheng Rong
Published: February 2024

Von Hippel-Lindau disease is a hereditary syndrome associated with various benign and malignant tumors, including hemangioblastomas. A 42-year-old man with a history of Von Hippel-Lindau disease underwent surgery for pancreatic neuroendocrine tumor and renal clear cell carcinoma and was recommended to undergo Al18F-NOTA-octreotide and 18F-FDG PETCT examination to assess potential metastases. 18F-FDG PET/CT showed low uptake in the right cerebellum, which demonstrated increased Al18F-NOTA-octreotide activity. Cerebellar mass resection surgery was performed. Pathological result was consistent with hemangioblastoma. This case report indicates the significant role of Al18F-NOTA-octreotide in the diagnosis of hemangioblastoma.
Targeted genome sequencing for tuberculosis drug susceptibility testing in South Africa: A proposed diagnostic pipeline
Authors: Bagratee Tayarv , Studholme David
Published: February 2024

In July 2023, the World Health Organization (WHO) began recommending targeted next-generation sequencing (tNGS), due to its ability to detect resistance to many drugs with a single test. In March 2023, South Africa further adopted the GeneXpert® XDR cartridge, which detects mutations associated with resistance to second-line injectable drugs. Here, we consider the feasibility for implementing tNGS in South Africa, what such a facility might look like and the specific context of this upper-middle-income country. Whilst the WHO now recommends tNGS for TB diagnostics and DST, there are many economic and infrastructural challenges opposing its deployment. In lieu of this, we instead recommend a stratified diagnostic pipeline that utilises South Africa's existing GeneXpert technologies, in an attempt to reduce the costs associated with implementation of tNGS.
LukProt: A database of eukaryotic predicted proteins designed for investigations of animal origins
Authors: Sobala Łukasz F.
Published: February 2024

Abstract

The origins and early evolution of animals is a subject with many outstanding questions. One problem faced by researchers trying to answer them is the absence of a comprehensive database with sequences from non-bilaterians. Publicly available data is plentiful but scattered and often not associated with proper metadata. A new database presented in this paper, LukProt, is an attempt at solving this issue. The database contains protein sequences obtained mostly from genomic, transcriptomic and metagenomic studies and is an extension of EukProt (Richter et al., 2022,Peer Community Journal,2, e56). LukProt adopts the EukProt naming conventions and includes data from 216 additional animals. The database is associated with a taxonomic grouping (taxogroup) scheme suitable for studying early animal evolution. Minor updates to the database will contain species additions or metadata corrections and major updates will synchronize LukProt to each new version of EukProt and releases are permanently stored on Zenodo. A BLAST server to search the database is available athttps://lukprot.hirszfeld.pl/. Users are invited to participate in maintaining and correcting LukProt. As it can be searched without downloading locally, the database can be a convenient resource not only for evolutionary biologists, but for the broader scientific community as well.

Graphical abstract

Significance statement

LukProt is a sequence database aiming to accelerate the research on the evolution of animals by cutting the time-consuming step of assembling sequences from disparate sources. Non-bilaterians are currently not well covered by general purpose databases, despite plentiful, public sequencing data. These data were integrated into a consistently curated database, presented here. It can be downloaded and used locally or used via a public BLAST search server. A clear taxonomic framework is also introduced, as well as scripts to aid local data analyses. LukProt will be publicly available on Zenodo, kept up to date and synchronized with each new version of its parent database, EukProt.
Flow Cytometry Strategies for Rapidly Characterizing Heterogeneous Adipocyte Populations in 3D In Vitro Constructs
Authors: Struss Michael M , Anvari Golnaz , Bellas Evangelia
Published: February 2024

Adipose tissue (AT) is an endocrine organ that regulates whole body metabolism and supports energy needs of other tissues. Two key adipose tissue functions are insulin-stimulated glucose uptake and lipid metabolism. As the prevalence of metabolic diseases, such as obesity, continue to rise, there is a growing need for new methods to study adipose tissue and its main cell type, adipocytes. Adipocytes are unique cells, distinguished by their large spherical shape housing large lipid droplet(s). For many in vitro models (and in tissues), adipocytes are derived from a heterogenous population of precursor cells, leading to varying degrees of adipogenesis and adipocyte maturation. Characterization of such populations can be challenging because often the average result does not account for the complexity of the various sub-populations. Common single cell characterization methods provide data based gene and protein expression but do not account for the morphological variability in cells such as adipocytes at different stages of maturation, and are expensive to run. More traditional methods, such as microscopy or colorimetric assays, are often time consuming with intrinsic challenges due to overlapping or coincident features or lose single cell adipocyte details due to the destructive nature of the assay. Here, we show how flow cytometry can be used to characterize adipocyte populations while preserving critical details at the individual adipocyte level. This protocol provides multiple workflows for indirect measurements of lipogenesis (lipid accumulation), protein content (branched actin formation), and adipocyte functions (insulin-stimulated glucose uptake). These flow cytometry workflows show the effectiveness of binning individual adipocytes based on their level of maturity and allow for comparisons within subpopulations traditional methods cannot provide.
Determining the importance of risk factors for the occurrence of temporomandibular disorders in the population and among exposed individuals
Authors: Miller James R. , Hass Zachary J.
Published: February 2024

There are many case-control (Ca-Co) studies in the literature on the importance of risk factors for the occurrence of temporomandibular disorders (TMD). These studies typically report the adjusted odds ratio (OR) for each risk factor being studied. This paper presents other epidemiological measurements for evaluating the importance of risk factors for the occurrence of TMD. These measurements include the population attributable risk percent (PAR%) and the attributable risk percent (AR%). The AR% for parafunctional habits, facial trauma, and orthopedic instability were estimated to be 86%, 80%, and 60%, respectively, while the corresponding PAR% were estimated to be 60%, 38%, and 7%. PAR% underestimates the importance of a risk factor for the occurrence of TMD among individuals exposed to the risk factor. The attributable risk percent (AR%) is an appropriate epidemiological measurement to evaluate the importance of a risk factor for TMD among individuals exposed to the risk factor.
Environmental, host, and symbiont drivers of heat tolerance in a species complex of reef-building corals
Authors: Naugle MS , Denis H , Mocellin VJL , Laffy PW , Popovic I , Bay LK , Howells EJ
Published: February 2024

Reef-building coral populations are under unprecedented threat from climate warming. Yet, variation in coral heat tolerance exists whereby some colonies can cope with higher sea temperatures than others and thus may hold unique value for conservation and restoration. Here, we quantify variation in heat tolerance of an ecologically important tabular coral species complex across the Great Barrier Reef (GBR) while also measuring genomic variation in the coral host and symbiont partners. Coral bleaching and photochemical traits were measured in 569 colonies within theAcropora hyacinthusspecies complex from 17 reefs following exposure to standardized acute heat stress assays. We detected substantial variation in heat tolerance, where individual colony thermal thresholds differed by up to 7.3°C and 5.7°C among and within reefs, respectively. Sea surface temperature climatology was the strongest predictor of heat tolerance, where colonies from warmer northern and inshore reefs typically exhibited the highest thermal thresholds, while colonies from cooler southern reefs were able to tolerate greater temperature increases relative to their local summer temperatures. Heat tolerance was also positively associated with exposure to thermal stress in the weeks preceding measurements. Assignment of colonies to host genomic clusters revealed four putative species within theA. hyacinthuscomplex that did not vary in their responses to experimental heat stress. Symbiodiniaceae communities within colonies were comprised primarily of Cladocopium ITS2 variants that differed spatially but had minimal effect on heat tolerance. Between 36 - 80% of heat tolerance variation was explained by environmental, host, and symbiont genomic predictors, leaving 20 - 64% to be explained by additional underlying drivers such as functional genomic variation not measured here. These results may be used to inform conservation and restoration actions, including targeting heat tolerant individuals for selective breeding, and will provide a foundation for evaluating the genomic basis of heat tolerance.
Landscape-scale spatial variations of pre-Columbian anthropogenic disturbances at three ring ditch sites in French Guiana
Authors: Marc Testé , Julien Engel , Kevin Mabobet , Mickael Mestre , Louise Brousseau
Published: February 2024

In the past two decades, repeated discoveries of numerous geometric earthworks in interfluvial regions of Amazonia have shed new light onto the territorial extent and the long-term impact of pre-Columbian populations on contemporary landscapes. In particular, the recent development of LiDAR imagery has accelerated the discovery of earthworks in densely forested hinterlands throughout the Amazon basin and the Guiana Shield.

This study aimed to evaluate the extent and landscape-scale spatial variations of pre-Columbian disturbances at three ring ditch sites in the French Guiana hinterland. We carried out extensive soil surveys along approximately 1 km-long transects spanning from ring ditches through the surrounding landscapes, and drawn upon multiple indicators, including archaeological artifacts, macro- and micro-charcoals, soil colorimetry, and physicochemical properties to retrace the pre-Columbian history of these sites in terms of occupation periods, anthropogenic soil alteration, and ancient land use.

Our results revealed a perennial occupation of these sites over long periods ranging from the 5th and 15th centuries CE, with local enrichments in chemical indicators (Corg, N, Mg, K, Ca) both within the enclosures of ring ditches and in the surrounding landscapes. Physicochemical properties variations were accompanied by variations in soil colorimetry, with darker soils within the enclosure of ring ditches interra-firmeareas. Interestingly however, soil properties did not meet all the characteristics of the so-called Amazonian Dark Earths, thus advocating a paradigm shift towards a better integration of Amazonian Brown Earths into the definition of anthropogenic soils in Amazonia. Soil disturbances were also associated to local enrichments in macro- and micro-charcoals that supportin situfire management that could be attributed to forest clearance and/or slash-and-burn cultivation.

Taken together, our results support the idea that pre-Columbian societies made extensive use of their landscapes in the interfluvial regions of the French Guiana hinterlands.
The proteome is a terminal electron acceptor
Authors: Flamholz Avi I. , Goyal Akshit , Fischer Woodward W. , Newman Dianne K. , Phillips Rob
Published: February 2024

Microbial metabolism is impressively flexible, enabling growth even when available nutrients differ greatly from biomass in redox state.E. coli, for example, rearranges its physiology to grow on reduced and oxidized carbon sources through several forms of fermentation and respiration. To understand the limits on and evolutionary consequences of metabolic flexibility, we developed a mathematical model coupling redox chemistry with principles of cellular resource allocation. Our integrated model clarifies key phenomena, including demonstrating that autotrophs grow slower than heterotrophs because of constraints imposed by intracellular production of reduced carbon. Our model further indicates that growth is improved by adapting the redox state of biomass to nutrients, revealing an unexpected mode of evolution where proteins accumulate mutations benefiting organismal redox balance.

One sentence summary

Microbial proteins adapt their composition on physiological and evolutionary timescales to ensure organismal redox balance.
NELF coordinates Pol II transcription termination and DNA replication initiation
Authors: Nakayama Chihiro , Daigaku Yasukazu , Aoi Yuki , Fang Qi , Kimura Hiroshi , Shilatifard Ali , Tellier Michael , Nojima Takayuki
Published: February 2024

Regulation of RNA polymerase II (Pol II) transcription is closely associated with cell proliferation. However, it remains unclear how the Pol II transcription program is altered in cancer to favour cell growth. Here, we find that gene expression ofNELFCD, a known negative elongation factor, is up-regulated in colorectal tumours. To dissect the direct role of NELF-C on Pol II transcription in such cancer, we employed an auxin-dependent protein degradation system for NELF-C in combination with nascent transcript sequencing technologies. Strikingly, we demonstrated that the acute loss of NELF-C protein globally perturbs Pol II transcription termination and also increases transcription elongation rate, independently of promoter-proximal Pol II pausing. This results in Pol II transcription into DNA replication initiation zones, and may link to failure of the cell cycle transition into S phase. We anticipate that NELF will be a potential therapeutic target to restrict colorectal cancers by promoting transcription-replication conflict.

HIGHLIGHTS

Expression ofNELFCDtranscript is up-regulated in colorectal tumors

NELF-C protein is mandatory for the transition between G1-S phases during cell cycle

NELF-C loss impairs transcription termination independently of Pol II promoter-proximal pausing

NELF-C loss leads Pol II to invade DNA replication initiation zones
Insights on the GPCR helix 8 solution structure and orientation using a neurotensin receptor 1 peptide
Authors: Bower James B. , Robson Scott A. , Ziarek Joshua J.
Published: February 2024

G-protein coupled receptors (GPCRs) are the largest class of membrane proteins in the human genome with high pharmaceutical relevance and implications to human health. These receptors share a prevalent architecture of seven transmembrane helices followed by an intracellular, amphipathic helix 8 (H8) and a disordered C-terminus. Technological advancements have led to over 1000 receptor structures in the last two decades, yet frequently H8 and the C-tail are conformationally heterogeneous or altogether absent. Here we synthesize a peptide comprising the neurotensin receptor 1 (NTS1) H8 and C-terminus (H8-Ctail) to investigate its structural stability, conformational dynamics and orientation in the presence of detergent and phospholipid micelles, which mimic the membrane. Circular dichroism (CD) and nuclear magnetic resonance (NMR) measurements confirm that zwitterionic 1,2-diheptanoyl-sn-glycero-3-phosphocholine is a potent stabilizer of H8 structure, whereas the commonly-used branched detergent lauryl maltose neopentyl glycol (LMNG) is unable to completely stabilize the helix – even at amounts four orders of magnitude greater than its critical micellar concentration. We then used NMR spectroscopy to assign the backbone chemical shifts. A series of temperature and lipid titrations were used to define the H8 boundaries as F376-R392 from chemical shift perturbations, changes in resonance intensity, and chemical-shift derived phi/psi angles. Finally, the H8 azimuthal and tilt angles, defining the helix orientation relative of the membrane normal were measured using paramagnetic relaxation enhancement (PRE) NMR. Taken together, our studies reveal the H8C-tail region is sensitive to membrane physicochemical properties and is capable of more adaptive behavior than previously suggested by static structural techniques.
Ophthalmic Manifestations of NAA10-Related and NAA15-Related Neurodevelopmental Syndrome: Analysis of Cortical Visual Impairment and Refractive Errors
Authors: Patel Rahi , Park Agnes Y. , Marchi Elaine , Gropman Andrea L. , Whitehead Matthew T. , Lyon Gholson J.
Published: February 2024

NAA10-related andNAA15-related neurodevelopmental syndrome, otherwise known as Ogden Syndrome, is known to present with varying degrees of intellectual disability, hypotonia, congenital cardiac abnormalities, seizures, and delayed speech and motor development. However, the ophthalmic manifestations ofNAA10andNAA15mutations are not yet fully characterized or understood. This study analyzed the prevalence of six ophthalmic conditions (cortical visual impairment, myopia, hyperopia, strabismus, nystagmus, and astigmatism) in 67 patients with pathogenic mutations in theNAA10cohort (54 inherited, 10 de novo; 65 missense, 2 frameshift) and 19 patients with pathogenic mutations in theNAA15cohort (18 de novo; 8 frameshift, 4 missense, 4 nonsense, and 1 splice site). Patients were interviewed virtually or in-person to collect a comprehensive medical history verified by medical records. These records were then analyzed to calculate the prevalence of these ophthalmic manifestations in each cohort. Analysis revealed a higher prevalence of ophthalmic conditions in ourNAA10cohort compared to existing literature (myopia 25.4% vs. 4.7%; astigmatism 37.3% vs. 13.2%; strabismus 28.4% vs. 3.8%; CVI 22.4% vs. 8.5%, respectively). No statistically significant differences were identified between theNAA10andNAA15mutations. Our study includes novel neuroimaging of 13NAA10and 5NAA15probands, which provides no clear correlation between globe size and severity of comorbid ophthalmic disease. Finally, anecdotal evidence was compiled to underscore the importance of early ophthalmologic evaluations and therapeutic interventions.